This document summarizes key points about HIV-associated lymphoma:
- HIV-associated lymphomas have improved in prognosis due to combination antiretroviral therapy and novel therapies, with many patients now cured.
- Diffuse large B-cell lymphoma and Burkitt lymphoma have excellent outcomes, similar to HIV-negative patients, especially with the addition of rituximab.
- New treatments are still needed to improve outcomes for patients with advanced immunosuppression or adverse tumor subtypes driven by viruses.
Lymphomas are the seventh most common cancer. The incidence of lymphomas is higher in industrialized countries, adults, and men compared to developing countries, children, and women respectively. Lymphomas are classified as either precursor cell neoplasms or mature cell neoplasms, with the latter including B cell lymphomas, T cell lymphomas, and Hodgkin lymphoma. Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and represents around 20-25% of new diagnoses in western countries. FL arises from germinal center B cells that have undergone somatic hypermutation but remain in an undifferentiated state.
This document discusses molecular basis of lymphoma. It begins with an introduction to lymphomas and statistics on incidence. It then discusses advances in subtyping non-Hodgkin's lymphomas (NHL), with diffuse large B-cell lymphoma accounting for 40% of cases. Key genes involved in lymphomagenesis are discussed, including BCL6, PRDM1, MYC, and XBP1. MicroRNAs and their role in regulating B-cell differentiation are also covered. The document concludes with discussions of specific lymphomas like follicular lymphoma, diffuse large B-cell lymphoma, and Hodgkin's lymphoma in terms of their immunophenotype, genetics, and staging.
This document discusses lymphoma and its classification. It notes that lymphoma arises from lymphoid tissue and is the most common hematologic malignancy in developed countries. There are two main types, Hodgkin's and non-Hodgkin's lymphoma, with non-Hodgkin's lymphoma accounting for about 85% of cases. The two most common forms of non-Hodgkin's lymphoma are follicular lymphoma and diffuse large B-cell lymphoma. Classification of lymphoma has evolved based on immunophenotypic and genetic features. Many lymphomas express the antigen CD20, which has made it a target for developing monoclonal antibody therapies.
Review And Clinical Assessment Of Patients With Sickle-Cell Disease At Childr...IJSRED
1) The study assessed 78 cases of hemoglobinopathies at a children's hospital in Benghazi, Libya, including 58 cases of sickle cell anemia. The majority of cases were of African descent from southern and Saharan areas of Libya.
2) Common complications among symptomatic sickle cell anemia cases included chronic pain, strokes, infections like hepatitis and HIV, and acute chest syndrome. One patient died from sepsis post-splenectomy.
3) There is a need for a national registry and prevention program in Libya to help manage sickle cell disease through strategies like preventing marriage between carriers to reduce risk of affected children.
HIV can increase the risk of developing lymphomas through sustained B-cell activation and high cytokine levels. AIDS-related lymphomas are categorized based on location into systemic, primary central nervous system, and body cavity-based types. The two major histological groups are immunoblastic lymphoma and small non-cleaved cell lymphoma (Burkitt lymphoma). Human herpes viruses have been linked to some forms of AIDS-related lymphomas.
When Two Diseases Cross their Paths: The Diagnostic Challenge of Rheumatoid A...Crimson-Arthritis
When Two Diseases Cross their Paths: The Diagnostic Challenge of Rheumatoid Arthritis in Sickle Cell Disease Patients by Isabel M McFarlane in Researches in Arthritis & Bone Study
This document summarizes HIV-associated cancers. It discusses how the introduction of antiretroviral therapy in the 1990s led to a decrease in AIDS-defining cancers like Kaposi's sarcoma and aggressive B-cell lymphomas, but also an increase in non-AIDS defining cancers as the population of people living with HIV aged. It focuses on Kaposi's sarcoma, describing its epidemiology and pathogenesis associated with Kaposi's sarcoma-associated herpesvirus, clinical manifestations, staging, and treatments including the importance of antiretroviral therapy and systemic therapies for advanced disease.
This document discusses tumors and cancers that are more common in HIV/AIDS patients. It states that those with HIV/AIDS have a higher risk of developing Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. It provides details on the symptoms, risk factors, and treatments for these types of cancers associated with HIV/AIDS. The survival rates for Kaposi sarcoma and outcomes for non-Hodgkin lymphoma have improved with newer HIV treatments.
Lymphomas are the seventh most common cancer. The incidence of lymphomas is higher in industrialized countries, adults, and men compared to developing countries, children, and women respectively. Lymphomas are classified as either precursor cell neoplasms or mature cell neoplasms, with the latter including B cell lymphomas, T cell lymphomas, and Hodgkin lymphoma. Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and represents around 20-25% of new diagnoses in western countries. FL arises from germinal center B cells that have undergone somatic hypermutation but remain in an undifferentiated state.
This document discusses molecular basis of lymphoma. It begins with an introduction to lymphomas and statistics on incidence. It then discusses advances in subtyping non-Hodgkin's lymphomas (NHL), with diffuse large B-cell lymphoma accounting for 40% of cases. Key genes involved in lymphomagenesis are discussed, including BCL6, PRDM1, MYC, and XBP1. MicroRNAs and their role in regulating B-cell differentiation are also covered. The document concludes with discussions of specific lymphomas like follicular lymphoma, diffuse large B-cell lymphoma, and Hodgkin's lymphoma in terms of their immunophenotype, genetics, and staging.
This document discusses lymphoma and its classification. It notes that lymphoma arises from lymphoid tissue and is the most common hematologic malignancy in developed countries. There are two main types, Hodgkin's and non-Hodgkin's lymphoma, with non-Hodgkin's lymphoma accounting for about 85% of cases. The two most common forms of non-Hodgkin's lymphoma are follicular lymphoma and diffuse large B-cell lymphoma. Classification of lymphoma has evolved based on immunophenotypic and genetic features. Many lymphomas express the antigen CD20, which has made it a target for developing monoclonal antibody therapies.
Review And Clinical Assessment Of Patients With Sickle-Cell Disease At Childr...IJSRED
1) The study assessed 78 cases of hemoglobinopathies at a children's hospital in Benghazi, Libya, including 58 cases of sickle cell anemia. The majority of cases were of African descent from southern and Saharan areas of Libya.
2) Common complications among symptomatic sickle cell anemia cases included chronic pain, strokes, infections like hepatitis and HIV, and acute chest syndrome. One patient died from sepsis post-splenectomy.
3) There is a need for a national registry and prevention program in Libya to help manage sickle cell disease through strategies like preventing marriage between carriers to reduce risk of affected children.
HIV can increase the risk of developing lymphomas through sustained B-cell activation and high cytokine levels. AIDS-related lymphomas are categorized based on location into systemic, primary central nervous system, and body cavity-based types. The two major histological groups are immunoblastic lymphoma and small non-cleaved cell lymphoma (Burkitt lymphoma). Human herpes viruses have been linked to some forms of AIDS-related lymphomas.
When Two Diseases Cross their Paths: The Diagnostic Challenge of Rheumatoid A...Crimson-Arthritis
When Two Diseases Cross their Paths: The Diagnostic Challenge of Rheumatoid Arthritis in Sickle Cell Disease Patients by Isabel M McFarlane in Researches in Arthritis & Bone Study
This document summarizes HIV-associated cancers. It discusses how the introduction of antiretroviral therapy in the 1990s led to a decrease in AIDS-defining cancers like Kaposi's sarcoma and aggressive B-cell lymphomas, but also an increase in non-AIDS defining cancers as the population of people living with HIV aged. It focuses on Kaposi's sarcoma, describing its epidemiology and pathogenesis associated with Kaposi's sarcoma-associated herpesvirus, clinical manifestations, staging, and treatments including the importance of antiretroviral therapy and systemic therapies for advanced disease.
This document discusses tumors and cancers that are more common in HIV/AIDS patients. It states that those with HIV/AIDS have a higher risk of developing Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. It provides details on the symptoms, risk factors, and treatments for these types of cancers associated with HIV/AIDS. The survival rates for Kaposi sarcoma and outcomes for non-Hodgkin lymphoma have improved with newer HIV treatments.
This document discusses B cell lymphoma and its classification. It notes that lymphomas are malignant disorders derived from lymphoid cells that can be B cell or T cell in origin, with the majority being of B cell origin. B cell lymphomas are divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is a distinct malignant disease that is predominantly of B cell origin and has a variable disease course but improved prognosis with modern treatments. Non-Hodgkin's lymphomas are more often clinically disseminated at diagnosis and can be of B cell or T cell origin.
The document summarizes a presentation on AIDS-related malignancies. It discusses trends seen in cancers affecting HIV/AIDS patients, including declines in AIDS-defining cancers like Kaposi's sarcoma and non-Hodgkin's lymphoma since the introduction of HAART. It also examines increases seen in certain non-AIDS defining cancers. Treatment options for Kaposi's sarcoma are reviewed, including the role of HAART and experimental approaches targeting KSHV mechanisms.
- Diffuse large B-cell lymphoma (DLBCL) can be classified into molecular subtypes including germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes, as well as double hit lymphomas that have a poor prognosis.
- New targeted agents in combination with R-CHOP have shown promising results for DLBCL subtypes, with proteasome inhibitors and immunomodulatory agents showing more activity in ABC DLBCL and BCL6 inhibitors, HDAC inhibitors, and etoposide showing potential in GCB DLBCL.
- For double hit and MYC-positive lymphomas, intensive chemotherapy such as dose-adjusted
Primary effusion lymphoma (formerly known as body cavity lymphoma), is an infrequent, aggressive B cell non-Hodgkin’s lym-phoma. The human herpes virus 8 (HHV8) or the Kaposi’s sarcoma associated herpes virus (KSHV) may be the potential determinant of the malignancy [1].
Post-transplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication of chronic immunosuppression in organ transplant recipients. It is most commonly seen as non-Hodgkin's lymphomas that are usually of B-cell origin. PTLD is caused by B cell proliferation induced by Epstein-Barr virus infection in the setting of immunosuppression. The degree of immunosuppression, EBV serostatus, time since transplant, and HLA matching all influence the risk of developing PTLD. Biopsy of lymph nodes and other involved tissues is important for diagnosis, while treatment involves reducing immunosuppression and using rituximab or chemotherapy.
The document discusses diffuse large B-cell lymphoma (DLBCL), its subtypes and classification. It describes how DLBCL can be categorized based on site of origin, characteristic features, association with viruses, or remain unclassified. Gene expression profiling can further distinguish DLBCL subgroups with different prognosis. The presence of MYC rearrangement or double hit lymphomas involving MYC and BCL2/BCL6 translocations predicts a very aggressive clinical outcome.
The document discusses acute leukemias of ambiguous lineage, specifically mixed phenotype acute leukemia (MPAL). It defines MPAL as acute leukemias that express antigens from more than one lineage, with at least 20% blasts. The most common combinations are B/myeloid and T/myeloid, seen in 59% and 35% of cases respectively. Diagnosis relies on extensive immunophenotyping using markers like MPO, cCD3, CD19. Patients are typically treated with a corticosteroid trial followed by an AML-like regimen if no response, and stem cell transplant offers the best outcome. The discussion presents examples of typical MPAL immunophenotypes and
1. The guideline provides recommendations for red blood cell transfusion thresholds and practices based on a systematic review of randomized clinical trials.
2. The strongest recommendation is for a restrictive transfusion strategy (7-8 g/dL hemoglobin level) for hospitalized, stable patients based on high-quality evidence of similar or better outcomes compared to a liberal strategy.
3. For patients with cardiovascular disease, the guideline suggests considering transfusion for patients with symptoms or hemoglobin ≤8 g/dL based on moderate-quality evidence.
4. For patients with acute coronary syndrome, the evidence was uncertain and no recommendation was made regarding a liberal or restrictive threshold.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy like CHOP has improved outcomes for DLBCL compared to chemotherapy alone in the post-rituximab era. Strategies to further improve outcomes include targeting specific genetic subgroups like the activated B-cell subtype using drugs like bortezomib that inhibit pathways like NF-kB.
This document discusses the ongoing risks of mortality from allogeneic blood transfusion and strategies to prevent them. It finds that the leading causes of transfusion-related death in the US are transfusion-related acute lung injury (TRALI), hemolytic transfusion reactions (HTRs), and transfusion-associated sepsis (TAS). Infectious causes now account for less than 15% of transfusion-related mortality. The document recommends further reducing mortality by avoiding donors alloimmunized to white blood cells from donating plasma, preventing HTRs, using white blood cell-reduced components for cardiac surgery patients, and implementing pathogen reduction technologies.
Acute lymphoblastic leukemia in children ch2tilayem
This document summarizes acute lymphoblastic leukemia (ALL) in children. It discusses the classification of ALL which includes morphological, immunological, and genetic classification. Morphological classification includes the FAB system which defines three categories of lymphoblasts. Immunological classification is based on monoclonal antibodies and distinguishes between B-lineage, T-lineage, and myeloid phenotypes. Genetic classification identifies cytogenetic abnormalities which are important for diagnosis, risk assessment, treatment and prognosis, with some abnormalities associated with favorable prognosis and others with poor prognosis.
Monocyte lymphocyte ratio with reference to tuberculosisDr. Zubair Younis
The document discusses the monocyte lymphocyte ratio (MLR) with reference to tuberculosis. It finds that the MLR is higher in active tuberculosis patients compared to healthy donors, and that an MLR less than the 9th percentile or greater than the 25th percentile can predict active tuberculosis. Studies also find that the MLR decreases with effective anti-tuberculosis therapy, suggesting it may be a marker of treatment effectiveness and prognosis. The MLR has also been associated with survival rates in various cancers.
Hepatocellular carcinoma an overview of disease epidemiology and risk factorspharmaindexing
This document provides an overview of hepatocellular carcinoma (HCC), the most common type of liver cancer, discussing its epidemiology and risk factors. It notes that HCC incidence varies globally and is highest in sub-Saharan Africa and Eastern Asia, where hepatitis B and C are most prevalent. Major risk factors for HCC include chronic hepatitis B and C infection, cirrhosis of the liver from any cause, aflatoxin B1 exposure, heavy alcohol use, and obesity. Tobacco smoking and diabetes may also increase HCC risk when combined with other factors like viral hepatitis. The pathogenesis of HCC involves chronic liver injury and inflammation triggering genetic changes over many years.
The document discusses screening and testing for infectious agents like hepatitis B, hepatitis C, and HIV. It describes the window period as the time between initial infection and when diagnostic tests can reliably detect the infection. For HIV, the window period may be up to 3 months depending on the test, but newer RNA tests can detect HIV within 12-16 days. For hepatitis B, the window period refers to the time between disappearing surface antigen and appearing antibodies, or between infection and appearing surface antigen. During this time, only IgM core antibodies may be detectable. The document also discusses various assays used in screening and testing like ELISA, EIA, RIA.
Transplantation of organs and tissues has become common for treating diseases. Complications include graft-versus-host disease (GVHD) and increased risk of infection and cancer due to lifelong immunosuppression. GVHD occurs when transplanted immune cells attack the recipient's body, commonly affecting the skin, bowel and liver. Opportunistic infections are frequent due to weakened immunity, including viruses like CMV and fungi such as Candida. Cancer risk is elevated 100-fold, with lymphoproliferative disorders, Kaposi's sarcoma and skin cancers being most common.
This study found that CMV coinfection is associated with higher CD8 T-cell counts, lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV-infected individuals. The key findings were:
1) Median CD8 counts were significantly higher in HIV/CMV coinfected patients compared to HIV monoinfected or healthy controls.
2) HIV/CMV coinfection resulted in significantly lower CD4/CD8 ratios.
3) Levels of inflammatory markers IP-10, TNF-RII, and D-dimer were higher in HIV/CMV coinfected individuals.
CMV coinfection may contribute to the risk of morbid outcomes in treated HIV infection by driving
Association between ABO Blood Group and Various Types of Cancer: A Case–Contr...asclepiuspdfs
This study investigated the association between ABO blood group and cancer risk in a Greek adult population. The study included 459 cancer patients and 918 non-cancer controls matched for age and gender. Multivariate analysis found that blood groups A and B were associated with significantly higher overall cancer risk compared to blood groups O and AB. Specifically, blood group A was associated with increased risk of gastric, colorectal, pancreatic, and lung cancer, while blood group B was associated with increased risk of esophageal cancer. The study provides evidence that ABO blood group is a risk factor for certain cancer types in Greek adults.
Acute myeloid leukemia (AML) is characterized by proliferation of immature myeloid cells in the bone marrow. The patient presented with AML-M2 subtype with FLT3-ITD mutation, resulting in neutropenia, thrombocytopenia, and oral candidiasis. Bone marrow tests found 61% blasts positive for myeloid markers and the FLT3 mutation. The goals of induction chemotherapy are to reduce morbidity and mortality by inducing remission and preventing relapse while managing complications of the disease and treatment.
This document provides an introduction to lymphoma and radioimmunotherapy. It discusses that lymphoma originates from lymphoid tissue and is the most common hematologic malignancy. It describes the classification of lymphomas and focuses on two common types - follicular lymphoma and diffuse large B-cell lymphoma. It then introduces radioimmunotherapy as a targeted treatment approach using radiolabeled monoclonal antibodies, with a focus on the anti-CD20 antibody rituximab which is commonly used to treat CD20-positive lymphomas.
- Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, representing 30-40% of cases worldwide.
- DLBCL presents as a rapidly growing tumor mass in lymph nodes or other tissues and is heterogeneous with various clinical presentations and genetic abnormalities.
- Gene expression profiling has identified two main subtypes of DLBCL, germinal center B-cell-like and activated B-cell-like, which have different genetic mutations and prognosis.
This document discusses B cell lymphoma and its classification. It notes that lymphomas are malignant disorders derived from lymphoid cells that can be B cell or T cell in origin, with the majority being of B cell origin. B cell lymphomas are divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is a distinct malignant disease that is predominantly of B cell origin and has a variable disease course but improved prognosis with modern treatments. Non-Hodgkin's lymphomas are more often clinically disseminated at diagnosis and can be of B cell or T cell origin.
The document summarizes a presentation on AIDS-related malignancies. It discusses trends seen in cancers affecting HIV/AIDS patients, including declines in AIDS-defining cancers like Kaposi's sarcoma and non-Hodgkin's lymphoma since the introduction of HAART. It also examines increases seen in certain non-AIDS defining cancers. Treatment options for Kaposi's sarcoma are reviewed, including the role of HAART and experimental approaches targeting KSHV mechanisms.
- Diffuse large B-cell lymphoma (DLBCL) can be classified into molecular subtypes including germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes, as well as double hit lymphomas that have a poor prognosis.
- New targeted agents in combination with R-CHOP have shown promising results for DLBCL subtypes, with proteasome inhibitors and immunomodulatory agents showing more activity in ABC DLBCL and BCL6 inhibitors, HDAC inhibitors, and etoposide showing potential in GCB DLBCL.
- For double hit and MYC-positive lymphomas, intensive chemotherapy such as dose-adjusted
Primary effusion lymphoma (formerly known as body cavity lymphoma), is an infrequent, aggressive B cell non-Hodgkin’s lym-phoma. The human herpes virus 8 (HHV8) or the Kaposi’s sarcoma associated herpes virus (KSHV) may be the potential determinant of the malignancy [1].
Post-transplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication of chronic immunosuppression in organ transplant recipients. It is most commonly seen as non-Hodgkin's lymphomas that are usually of B-cell origin. PTLD is caused by B cell proliferation induced by Epstein-Barr virus infection in the setting of immunosuppression. The degree of immunosuppression, EBV serostatus, time since transplant, and HLA matching all influence the risk of developing PTLD. Biopsy of lymph nodes and other involved tissues is important for diagnosis, while treatment involves reducing immunosuppression and using rituximab or chemotherapy.
The document discusses diffuse large B-cell lymphoma (DLBCL), its subtypes and classification. It describes how DLBCL can be categorized based on site of origin, characteristic features, association with viruses, or remain unclassified. Gene expression profiling can further distinguish DLBCL subgroups with different prognosis. The presence of MYC rearrangement or double hit lymphomas involving MYC and BCL2/BCL6 translocations predicts a very aggressive clinical outcome.
The document discusses acute leukemias of ambiguous lineage, specifically mixed phenotype acute leukemia (MPAL). It defines MPAL as acute leukemias that express antigens from more than one lineage, with at least 20% blasts. The most common combinations are B/myeloid and T/myeloid, seen in 59% and 35% of cases respectively. Diagnosis relies on extensive immunophenotyping using markers like MPO, cCD3, CD19. Patients are typically treated with a corticosteroid trial followed by an AML-like regimen if no response, and stem cell transplant offers the best outcome. The discussion presents examples of typical MPAL immunophenotypes and
1. The guideline provides recommendations for red blood cell transfusion thresholds and practices based on a systematic review of randomized clinical trials.
2. The strongest recommendation is for a restrictive transfusion strategy (7-8 g/dL hemoglobin level) for hospitalized, stable patients based on high-quality evidence of similar or better outcomes compared to a liberal strategy.
3. For patients with cardiovascular disease, the guideline suggests considering transfusion for patients with symptoms or hemoglobin ≤8 g/dL based on moderate-quality evidence.
4. For patients with acute coronary syndrome, the evidence was uncertain and no recommendation was made regarding a liberal or restrictive threshold.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy like CHOP has improved outcomes for DLBCL compared to chemotherapy alone in the post-rituximab era. Strategies to further improve outcomes include targeting specific genetic subgroups like the activated B-cell subtype using drugs like bortezomib that inhibit pathways like NF-kB.
This document discusses the ongoing risks of mortality from allogeneic blood transfusion and strategies to prevent them. It finds that the leading causes of transfusion-related death in the US are transfusion-related acute lung injury (TRALI), hemolytic transfusion reactions (HTRs), and transfusion-associated sepsis (TAS). Infectious causes now account for less than 15% of transfusion-related mortality. The document recommends further reducing mortality by avoiding donors alloimmunized to white blood cells from donating plasma, preventing HTRs, using white blood cell-reduced components for cardiac surgery patients, and implementing pathogen reduction technologies.
Acute lymphoblastic leukemia in children ch2tilayem
This document summarizes acute lymphoblastic leukemia (ALL) in children. It discusses the classification of ALL which includes morphological, immunological, and genetic classification. Morphological classification includes the FAB system which defines three categories of lymphoblasts. Immunological classification is based on monoclonal antibodies and distinguishes between B-lineage, T-lineage, and myeloid phenotypes. Genetic classification identifies cytogenetic abnormalities which are important for diagnosis, risk assessment, treatment and prognosis, with some abnormalities associated with favorable prognosis and others with poor prognosis.
Monocyte lymphocyte ratio with reference to tuberculosisDr. Zubair Younis
The document discusses the monocyte lymphocyte ratio (MLR) with reference to tuberculosis. It finds that the MLR is higher in active tuberculosis patients compared to healthy donors, and that an MLR less than the 9th percentile or greater than the 25th percentile can predict active tuberculosis. Studies also find that the MLR decreases with effective anti-tuberculosis therapy, suggesting it may be a marker of treatment effectiveness and prognosis. The MLR has also been associated with survival rates in various cancers.
Hepatocellular carcinoma an overview of disease epidemiology and risk factorspharmaindexing
This document provides an overview of hepatocellular carcinoma (HCC), the most common type of liver cancer, discussing its epidemiology and risk factors. It notes that HCC incidence varies globally and is highest in sub-Saharan Africa and Eastern Asia, where hepatitis B and C are most prevalent. Major risk factors for HCC include chronic hepatitis B and C infection, cirrhosis of the liver from any cause, aflatoxin B1 exposure, heavy alcohol use, and obesity. Tobacco smoking and diabetes may also increase HCC risk when combined with other factors like viral hepatitis. The pathogenesis of HCC involves chronic liver injury and inflammation triggering genetic changes over many years.
The document discusses screening and testing for infectious agents like hepatitis B, hepatitis C, and HIV. It describes the window period as the time between initial infection and when diagnostic tests can reliably detect the infection. For HIV, the window period may be up to 3 months depending on the test, but newer RNA tests can detect HIV within 12-16 days. For hepatitis B, the window period refers to the time between disappearing surface antigen and appearing antibodies, or between infection and appearing surface antigen. During this time, only IgM core antibodies may be detectable. The document also discusses various assays used in screening and testing like ELISA, EIA, RIA.
Transplantation of organs and tissues has become common for treating diseases. Complications include graft-versus-host disease (GVHD) and increased risk of infection and cancer due to lifelong immunosuppression. GVHD occurs when transplanted immune cells attack the recipient's body, commonly affecting the skin, bowel and liver. Opportunistic infections are frequent due to weakened immunity, including viruses like CMV and fungi such as Candida. Cancer risk is elevated 100-fold, with lymphoproliferative disorders, Kaposi's sarcoma and skin cancers being most common.
This study found that CMV coinfection is associated with higher CD8 T-cell counts, lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV-infected individuals. The key findings were:
1) Median CD8 counts were significantly higher in HIV/CMV coinfected patients compared to HIV monoinfected or healthy controls.
2) HIV/CMV coinfection resulted in significantly lower CD4/CD8 ratios.
3) Levels of inflammatory markers IP-10, TNF-RII, and D-dimer were higher in HIV/CMV coinfected individuals.
CMV coinfection may contribute to the risk of morbid outcomes in treated HIV infection by driving
Association between ABO Blood Group and Various Types of Cancer: A Case–Contr...asclepiuspdfs
This study investigated the association between ABO blood group and cancer risk in a Greek adult population. The study included 459 cancer patients and 918 non-cancer controls matched for age and gender. Multivariate analysis found that blood groups A and B were associated with significantly higher overall cancer risk compared to blood groups O and AB. Specifically, blood group A was associated with increased risk of gastric, colorectal, pancreatic, and lung cancer, while blood group B was associated with increased risk of esophageal cancer. The study provides evidence that ABO blood group is a risk factor for certain cancer types in Greek adults.
Acute myeloid leukemia (AML) is characterized by proliferation of immature myeloid cells in the bone marrow. The patient presented with AML-M2 subtype with FLT3-ITD mutation, resulting in neutropenia, thrombocytopenia, and oral candidiasis. Bone marrow tests found 61% blasts positive for myeloid markers and the FLT3 mutation. The goals of induction chemotherapy are to reduce morbidity and mortality by inducing remission and preventing relapse while managing complications of the disease and treatment.
This document provides an introduction to lymphoma and radioimmunotherapy. It discusses that lymphoma originates from lymphoid tissue and is the most common hematologic malignancy. It describes the classification of lymphomas and focuses on two common types - follicular lymphoma and diffuse large B-cell lymphoma. It then introduces radioimmunotherapy as a targeted treatment approach using radiolabeled monoclonal antibodies, with a focus on the anti-CD20 antibody rituximab which is commonly used to treat CD20-positive lymphomas.
- Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, representing 30-40% of cases worldwide.
- DLBCL presents as a rapidly growing tumor mass in lymph nodes or other tissues and is heterogeneous with various clinical presentations and genetic abnormalities.
- Gene expression profiling has identified two main subtypes of DLBCL, germinal center B-cell-like and activated B-cell-like, which have different genetic mutations and prognosis.
WHO 2016 update on classification of Lymphoid neoplasms Arijit Roy
This document summarizes the major proposed changes in the 2016 revision of the World Health Organization classification of lymphoid neoplasms compared to the 2008 classification. Some key changes include distinguishing low-count from high-count monoclonal B-cell lymphocytosis, recognizing provisional entities like large B-cell lymphoma with IRF4 rearrangement, and emphasizing prognostic markers for diffuse large B-cell lymphoma like double expression of MYC and BCL2 proteins. The revision aims to better classify hematologic malignancies based on new clinical, pathological and genetic data.
This document discusses immunodeficiency and HIV/AIDS. It defines immunodeficiency as a compromised immune system and describes how it is classified as either primary/congenital or secondary/acquired. HIV is described as a retrovirus that causes AIDS by infecting CD4 cells and impairing the immune system over time. The document outlines HIV transmission, structure, lifecycle, and global prevalence, with statistics provided on prevalence in Zambia.
This document provides an overview of Hodgkin lymphoma (HL), including:
- HL is a malignancy of mature B lymphocytes that represents 10% of lymphomas diagnosed annually.
- Classical HL has high cure rates of over 85% with radiation and chemotherapy. However, late therapy-related toxicities are a new challenge.
- Staging is important for selecting appropriate therapy intensity, with early stage patients having a better prognosis than advanced stage.
- Treatment depends on stage and risk factors, and may involve chemotherapy alone or with radiation for early stage disease. Advanced stage is treated with chemotherapy only.
- Late effects of therapy include secondary cancers and heart disease, so reducing radiation exposure is a focus of research.
This document reviews tumor lysis syndrome (TLS), a potentially life-threatening condition caused by the rapid breakdown of tumor cells during chemotherapy or other treatments. It discusses the pathogenesis and risk factors for TLS and provides recommendations for management. TLS is most common in patients with high-proliferating hematological malignancies like acute leukemias and lymphomas. Risk factors include the type and extent of cancer, chemotherapy regimen, age, and preexisting kidney impairment. Management involves aggressive hydration, monitoring and correcting electrolyte abnormalities, controlling uric acid levels, and dialysis for acute kidney injury. TLS requires prompt treatment to prevent complications and interruptions to cancer treatment.
This document reviews tumor lysis syndrome (TLS), a potentially life-threatening condition caused by the rapid breakdown of tumor cells during chemotherapy or other treatments. It discusses the pathogenesis and risk factors for TLS, including certain types of cancers like acute leukemias and lymphomas that are more likely to cause TLS. The review covers clinical features of TLS like hyperuricemia, hyperkalemia, hypocalcemia, and acute kidney injury. It also discusses guidelines for risk assessment and management of TLS, including hydration, monitoring of electrolytes, use of drugs like allopurinol and rasburicase to prevent complications, and dialysis in severe cases. Elderly patients are noted to be at higher risk given age-related
Journal Reading Stem Cell dengan HIV (sharon) soroylardo1
1) Studies in murine and macaque models show that genetically modifying CD4+ T-cells to disrupt CCR5, the main HIV coreceptor, provides a selective advantage over non-modified cells and significantly reduces plasma viremia. However, a source of residual viral reservoir remains.
2) Two HIV patients who underwent allogeneic stem cell transplantation from CCR5-negative donors have remained virus-free for nearly 4 years after transplantation while kept on antiretroviral therapy (ART), suggesting genetic modification may not be necessary if ART is completely suppressive.
3) Hematopoietic stem cell transplantation remains a promising curative approach for HIV, but the timing of ART interruption
This document provides updated guidelines for managing hepatitis B virus (HBV) infection. It summarizes that chronic HBV infection can be classified into five phases based on levels of HBeAg and HBV DNA. All patients with chronic HBV are at risk of cirrhosis and liver cancer, so the goals of treatment are to prevent disease progression and improve survival. The guidelines recommend long-term treatment with entecavir, tenofovir disoproxil, or tenofovir alafenamide as the standard of care.
This document provides updated guidelines for managing hepatitis B virus (HBV) infection. It summarizes that chronic HBV infection can be classified into five phases based on levels of HBeAg and HBV DNA. All patients with chronic HBV are at risk of cirrhosis and liver cancer, so the goals of treatment are to prevent disease progression and improve survival. The guidelines recommend long-term treatment with entecavir, tenofovir disoproxil, or tenofovir alafenamide as the standard of care.
This document summarizes updated guidelines from the European Association for the Study of the Liver (EASL) on the management of hepatitis B virus (HBV) infection. It classifies chronic HBV infection into five phases based on markers like HBeAg and HBV DNA levels. All chronic HBV patients are at risk of cirrhosis and liver cancer, with risks varying based on host and viral factors. The guidelines provide recommendations on treatment indications, goals, and options including long-term use of potent antivirals. Ongoing monitoring of treated and untreated patients is important to prevent disease progression and complications like liver cancer.
Uctioleuco Reduction of Blood Products- A Rising Essentiality in Transfusion ...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
This study examined the association between blood group antigens, CD4 cell count, and hemoglobin patterns in HIV-infected patients. 240 newly diagnosed HIV-positive patients and 120 healthy controls were analyzed. There was no significant association found between ABO/Rh blood groups or hemoglobin genotypes between the two groups. However, a significant association was observed between CD4 cell count and ABO blood group, with blood groups A and AB having higher average CD4 counts. The study suggests blood group A may confer some immunity against HIV infection.
Post-transplant lymphoproliferative disorder/disease (PTLD) is a B-cell proliferation disorder following infection with EpsteineBarr virus due to therapeutic immunosuppression after organ transplantation. The more intense the immunosuppression, the higher the incidence of PTLD and the earlier it occurs. The cornerstone of successful treatment of PTLD is reduction or withdrawal of immunosuppression.
This document summarizes the major changes in the 2016 revision of the World Health Organization classification of hematological malignancies, with a focus on lymphoid neoplasms. Key changes include: refining diagnostic criteria for several entities based on new genetic and molecular data; recognizing new provisional entities; emphasizing distinct subtypes within certain lymphomas that have different clinical behaviors and molecular profiles; and clarifying the definitions of certain pre-malignant conditions. The revision aims to improve diagnosis and help guide treatment strategies based on the most up-to-date understanding of these diseases.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation are common in patients with cancer undergoing chemotherapy and immunosuppressive therapy. Rates of HBV reactivation range from 14-72% in HBV carriers receiving chemotherapy, and mortality rates range from 5-52%. HCV reactivation seems to be less common than HBV reactivation. HBV and HCV reactivation can lead to modifications or interruptions of chemotherapy, negatively impacting patient outcomes. Risk factors for viral reactivation need to be better defined to identify patients who may benefit from preventive antiviral therapy.
Structure
Content:
1.0 introduction
1/ (sentence) sentence Hook
3/ (sen) Background
2/ (sen) Scope
1/ (sen) Thesis statement
2.0 Body
Figures tables data pictures……
3.0 Conclusion
4.0 Reference
PS:This is not a Lab report, is just a normal report.
R E V I E W A R T I C L E
Gene therapy for hemophilia
Marinee K. L. Chuah
Desire Collen
Thierry VandenDriessche*
Center for Transgene Technology and
Gene Therapy, Flanders
Interuniversity Institute for
Biotechnology, University of Leuven,
49 Herestraat, B-3000 Leuven,
Belgium
*Correspondence to: T.
VandenDriessche, Center for
Transgene Technology and Gene
Therapy, Flanders Interuniversity
Institute for Biotechnology,
University of Leuven, 49 Herestraat,
B-3000 Leuven, Belgium.
E-mail: thierry.vandendriessche
@med.kuleuven.ac.be or
[email protected]
kuleuven.ac.be
Received: 3 October 2000
Revised: 13 November 2000
Accepted: 14 November 2000
Summary
Hemophilia A and B are X-chromosome linked recessive bleeding disorders
that result from a de®ciency in factor VIII (FVIII) and factor IX (FIX)
respectively. Though factor substitution therapy has greatly improved the
lives of hemophiliac patients, there are still limitations to the current
treatment that have triggered interest in alternative treatments by gene
therapy. Signi®cant progress has recently been made in the development of
gene therapy for the treatment of hemophilia A and B. These advances
parallel the technical improvements of existing vector systems including
MoMLV-based retroviral, adenoviral and AAV vectors, and the development
of new delivery methods such as lentiviral vectors, helper-dependent
adenoviral vectors and improved non-viral gene delivery methods. Thera-
peutic and physiologic levels of FVIII and FIX could be achieved in FVIII- and
FIX-de®cient mice and hemophilia dogs by different gene therapy
approaches. Long-term correction of the bleeding disorders and in some
cases a permanent cure has been realized in these preclinical studies.
However, the induction of neutralizing antibodies often precludes stable
phenotypic correction. Another complication is that certain promoters are
prone to transcriptional inactivation in vivo, precluding long-term FVIII or FIX
expression. Several gene therapy phase I clinical trials are currently ongoing
in patients suffering from severe hemophilia A or B. No signi®cant adverse
side-effects were reported, and semen samples were negative for vector
sequences by sensitive PCR assays. Most importantly, some subjects report
fewer bleeding episodes and occasionally have very low levels of clotting
factor activity detected. The results from the extensive preclinical studies in
normal and hemophilic animal models and encouraging preliminary clinical
data indicate that the simultaneous development of different strategies is
likely to bring a permanent cure for hemophilia one step closer to reality.
Copyright # 2001 John Wiley & So.
Assessment of serum lipid profile in patients with chronic hepatitis cTanveer00786
1. The document discusses a study that assessed the serum lipid profiles of 100 patients diagnosed with chronic hepatitis C.
2. It found that 63% of patients had normal lipid levels, 3% were hyperlipidemic, and 34% were hypolipidemic.
3. The study indicates that progression of hepatitis C viral infection can lead to decreased levels of lipids.
A sample of an annotated bibliography entry for HCM402, using the .docxblondellchancy
This document summarizes an annotated bibliography entry for a research article on reducing catheter-related bloodstream infections in intensive care units. The summary addresses each section of the annotated bibliography guidelines, including that the study is well-cited, has a clear problem statement and hypothesis, clearly defines independent and dependent variables, and has a large representative sample. The results support the hypothesis that infection rates decreased significantly with the intervention of training protocols and checklists.
This document discusses viruses associated with lymphoma. It focuses on Epstein-Barr virus (EBV) which is present in tumor cells of some lymphomas. EBV infects B cells and can immortalize them in vitro, expressing genes that drive proliferation. While EBV infection is common, only a small subset develops lymphoma, showing lymphomagenesis requires additional factors. EBV is strongly associated with several lymphoma subtypes, variably associated with others, and rarely associated with some. Post-transplant lymphoproliferative disorder is often EBV-associated due to immunosuppression allowing infected B cells to proliferate.
Este documento revisa las recomendaciones actualizadas sobre el diagnóstico y tratamiento de los linfomas en pacientes infectados por el VIH de acuerdo a los grupos GESIDA y PETHEMA. Se discuten los linfomas no hodgkinianos sistémicos como la segunda neoplasia más común tras el sarcoma de Kaposi, destacando el linfoma B difuso de célula grande como el subtipo más frecuente. El tratamiento con antirretrovirales ha mejorado significativamente el pronóstico de estos linfomas al controlar
El documento describe los cambios en la incidencia, tipo e historia natural de los linfomas no Hodgkin (LNH) asociados con el VIH/SIDA desde la introducción de la terapia antirretroviral de alta efectividad (TARGA). Aunque la TARGA redujo la incidencia de algunos LNH y otras neoplasias relacionadas con el SIDA, no tuvo el mismo efecto en todos los subtipos de LNH. Los LNH asociados con el SIDA suelen ser de alto grado, presentarse en etapas avanzadas y tener un pronóst
La fascitis necrotizante es una infección rápidamente progresiva de la piel y los tejidos blandos que causa destrucción y necrosis de la fascia y la grasa subcutánea, asociada con importante toxicidad sistémica y alta mortalidad. Puede ser causada por una infección polimicrobiana o por estreptococos. Los factores de riesgo incluyen diabetes, inmunosupresión y cirugías recientes. El diagnóstico y tratamiento tempranos son cruciales para el pronóstico, que incluye soporte hemodin
Este documento trata sobre las recomendaciones para el diagnóstico y tratamiento de las infecciones de piel y partes blandas (IPPB). Se clasifican las IPPB en infecciones superficiales (impétigo, erisipela, celulitis) e infecciones profundas y necrosantes (fascitis, mionecrosis). Para el impétigo, el diagnóstico suele ser clínico y los tratamientos tópicos más efectivos son la mupirocina y el ácido fusídico. En general, el documento busca generar guías actualiz
1. The document provides clinical practice guidelines from the Infectious Diseases Society of America for the diagnosis and management of prosthetic joint infections.
2. It includes recommendations for diagnosing PJI through preoperative evaluation, intraoperative testing, and defines what constitutes a PJI. Surgical treatment strategies are also addressed, including debridement with retention, one-stage or two-stage exchange, and resection arthroplasty.
3. Medical treatment guidelines are provided for staphylococcal PJI following debridement, including pathogen-specific intravenous antibiotics combined with rifampin followed by chronic oral suppression if needed.
This document discusses the polymicrobial nature of biofilm infections. It summarizes that biofilms are usually polymicrobial communities that provide advantages like passive resistance, metabolic cooperation, and an enlarged gene pool through horizontal gene transfer. DNA methods using PCR and sequencing have demonstrated the ability to identify microorganisms in clinical biofilm infections. A robust model of polymicrobial biofilm infection along with accurate diagnosis is improving clinical outcomes.
Este documento discute la epidemiología, etiología, clasificación, diagnóstico y tratamiento de las infecciones de prótesis articulares. Las infecciones de prótesis son una complicación grave que puede causar defectos esqueléticos y reducir la calidad de vida. La incidencia ha disminuido gracias a mejoras quirúrgicas y de prevención, pero sigue siendo del 1,5-2,5%. El diagnóstico es difícil porque los síntomas son inespecíficos, aunque cultivos positivos confirman la in
1) Staphylococcus aureus es un microorganismo virulento y resistente a antibióticos que causa una amplia variedad de enfermedades en humanos. 2) Las cepas de S. aureus resistentes a meticilina (MRSA) tradicionalmente se limitaban a hospitales pero ahora están apareciendo en la comunidad. 3) Si no se controla adecuadamente la cambiante epidemiología y síntomas clínicos de estas cepas de MRSA, podrían convertirse en un importante problema de salud.
La guía trata sobre el tratamiento de infecciones causadas por Staphylococcus aureus resistente a meticilina (SARM). En los últimos 5 años, las infecciones por SARM han experimentado cambios importantes que influyen en la elección del tratamiento, incluyendo un aumento de su frecuencia en hospitales y la aparición de cepas adquiridas en la comunidad. También se ha mejorado el conocimiento de los parámetros farmacocinética/farmacodinámica de los antibióticos y se han introducido nuevos antibióticos activos frente a
Este documento presenta una revisión del síndrome de reconstitución inmunológica (SRI) asociado con la infección por el VIH y el tratamiento antirretroviral de alta eficacia. Define el SRI como una complicación clínica adversa causada por la restauración de la respuesta inmune específica a antígenos que puede conducir al comienzo o empeoramiento de infecciones u otras enfermedades. Revisa la epidemiología, clasificación, criterios de diagnóstico y principales etiologías del SRI
Este documento presenta una revisión del síndrome de reconstitución inmunológica (SRI) asociado con la infección por el VIH y el tratamiento antirretroviral de alta eficacia. Define el SRI como una complicación clínica adversa causada por la restauración de la respuesta inmune específica a antígenos que puede causar el comienzo o empeoramiento de infecciones u otras enfermedades. Revisa la epidemiología, clasificación, criterios de diagnóstico y etiologías más frecuentes del
Este documento presenta el caso clínico de un paciente de 36 años con SIDA que consultó por un síndrome cerebeloso. Las imágenes cerebrales mostraron granulomas en el cerebelo y tronco encefálico. Se diagnosticó tuberculosis sistémica basada en bacilos ácido-alcohol resistentes encontrados en orina y biopsia de ganglio linfático. El tratamiento antituberculoso llevó a una buena evolución clínica y una notable reducción del tamaño de las lesiones.
Este documento resume los aspectos más relevantes de la infección por citomegalovirus humano (CMV). La prevalencia de CMV es muy alta a nivel mundial. Tras la infección primaria, el virus permanece latente de por vida, pudiendo causar recurrencias. Las infecciones más graves se dan en recién nacidos por transmisión congénita y en pacientes inmunodeprimidos, donde actúa como patógeno oportunista. Las técnicas serológicas son útiles para diagnosticar la infección primaria y
The report finds that antimicrobial resistance is a major public health threat, with very high rates of resistance observed in many common bacterial pathogens worldwide. Surveillance of antimicrobial resistance is inadequate, with significant gaps and lack of standardization. While disease-specific programs have better surveillance, multidrug-resistant tuberculosis in particular remains underreported. The increasing spread of resistance threatens global progress on infectious diseases and emphasizes the urgent need to strengthen coordinated surveillance efforts.
1) The study aimed to use the PP65 antigenemia technique to diagnose active cytomegalovirus (CMV) infection in AIDS patients in Brazil and examine its occurrence in the region.
2) They found that 14 of 50 AIDS patients tested positive for PP65 antigenemia, indicating active CMV infection, while none of the 34 bone marrow transplant patients tested positive.
3) Having a CD4+ T-cell count below 100 cells/mm3 appeared to increase the risk of testing positive for PP65 antigenemia and active CMV infection, as more low CD4 count patients tested positive compared to higher CD4 count patients.
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)MuskanShingari
Statistics- Statistics is the science of collecting, organizing, presenting, analyzing and interpreting numerical data to assist in making more effective decisions.
A statistics is a measure which is used to estimate the population parameter
Parameters-It is used to describe the properties of an entire population.
Examples-Measures of central tendency Dispersion, Variance, Standard Deviation (SD), Absolute Error, Mean Absolute Error (MAE), Eigen Value
Congestive Heart failure is caused by low cardiac output and high sympathetic discharge. Diuretics reduce preload, ACE inhibitors lower afterload, beta blockers reduce sympathetic activity, and digitalis has inotropic effects. Newer medications target vasodilation and myosin activation to improve heart efficiency while lowering energy requirements. Combination therapy, following an assessment of cardiac function and volume status, is the most effective strategy to heart failure care.
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14...Donc Test
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14th Edition (Hinkle, 2017) Verified Chapter's 1 - 73 Complete.pdf
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14th Edition (Hinkle, 2017) Verified Chapter's 1 - 73 Complete.pdf
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14th Edition (Hinkle, 2017) Verified Chapter's 1 - 73 Complete.pdf
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7shruti jagirdar
Unit 4: MRA 103T Regulatory affairs
This guideline is directed principally toward new Molecular Entities that are
likely to have significant use in the elderly, either because the disease intended
to be treated is characteristically a disease of aging ( e.g., Alzheimer's disease) or
because the population to be treated is known to include substantial numbers of
geriatric patients (e.g., hypertension).
Gene therapy can be broadly defined as the transfer of genetic material to cure a disease or at least to improve the clinical status of a patient.
One of the basic concepts of gene therapy is to transform viruses into genetic shuttles, which will deliver the gene of interest into the target cells.
Safe methods have been devised to do this, using several viral and non-viral vectors.
In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient's cells instead of using drugs or surgery.
The biggest hurdle faced by medical research in gene therapy is the availability of effective gene-carrying vectors that meet all of the following criteria:
Protection of transgene or genetic cargo from degradative action of systemic and endonucleases,
Delivery of genetic material to the target site, i.e., either cell cytoplasm or nucleus,
Low potential of triggering unwanted immune responses or genotoxicity,
Economical and feasible availability for patients .
Viruses are naturally evolved vehicles that efficiently transfer their genes into host cells.
Choice of viral vector is dependent on gene transfer efficiency, capacity to carry foreign genes, toxicity, stability, immune responses towards viral antigens and potential viral recombination.
There are a wide variety of vectors used to deliver DNA or oligo nucleotides into mammalian cells, either in vitro or in vivo.
The most common vector system based on retroviruses, adenoviruses, herpes simplex viruses, adeno associated viruses.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Giloy in Ayurveda - Classical Categorization and SynonymsPlanet Ayurveda
Giloy, also known as Guduchi or Amrita in classical Ayurvedic texts, is a revered herb renowned for its myriad health benefits. It is categorized as a Rasayana, meaning it has rejuvenating properties that enhance vitality and longevity. Giloy is celebrated for its ability to boost the immune system, detoxify the body, and promote overall wellness. Its anti-inflammatory, antipyretic, and antioxidant properties make it a staple in managing conditions like fever, diabetes, and stress. The versatility and efficacy of Giloy in supporting health naturally highlight its importance in Ayurveda. At Planet Ayurveda, we provide a comprehensive range of health services and 100% herbal supplements that harness the power of natural ingredients like Giloy. Our products are globally available and affordable, ensuring that everyone can benefit from the ancient wisdom of Ayurveda. If you or your loved ones are dealing with health issues, contact Planet Ayurveda at 01725214040 to book an online video consultation with our professional doctors. Let us help you achieve optimal health and wellness naturally.
Dr. Tan's Balance Method.pdf (From Academy of Oriental Medicine at Austin)GeorgeKieling1
Home
Organization
Academy of Oriental Medicine at Austin
Academy of Oriental Medicine at Austin
Academy of Oriental Medicine at Austin
About AOMA: The Academy of Oriental Medicine at Austin offers a masters-level graduate program in acupuncture and Oriental medicine, preparing its students for careers as skilled, professional practitioners. AOMA is known for its internationally recognized faculty, award-winning student clinical internship program, and herbal medicine program. Since its founding in 1993, AOMA has grown rapidly in size and reputation, drawing students from around the nation and faculty from around the world. AOMA also conducts more than 20,000 patient visits annually in its student and professional clinics. AOMA collaborates with Western healthcare institutions including the Seton Family of Hospitals, and gives back to the community through partnerships with nonprofit organizations and by providing free and reduced price treatments to people who cannot afford them. The Academy of Oriental Medicine at Austin is located at 2700 West Anderson Lane. AOMA also serves patients and retail customers at its south Austin location, 4701 West Gate Blvd. For more information see www.aoma.edu or call 512-492-303434.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Nutritional deficiency Disorder are problems in india.
It is very important to learn about Indian child's nutritional parameters as well the Disease related to alteration in their Nutrition.
Discover the benefits of homeopathic medicine for irregular periods with our guide on 5 common remedies. Learn how these natural treatments can help regulate menstrual cycles and improve overall menstrual health.
Visit Us: https://drdeepikashomeopathy.com/service/irregular-periods-treatment/
1. doi:10.1182/blood-2011-08-373738
Prepublished online February 15, 2012;
2012 119: 3245-3255
Kieron Dunleavy and Wyndham H. Wilson
How I treat HIV-associated lymphoma
http://bloodjournal.hematologylibrary.org/content/119/14/3245.full.html
Updated information and services can be found at:
(1501 articles)Lymphoid Neoplasia
(112 articles)How I Treat
(1916 articles)Free Research Articles
Articles on similar topics can be found in the following Blood collections
http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests
Information about reproducing this article in parts or in its entirety may be found online at:
http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints
Information about ordering reprints may be found online at:
http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml
Information about subscriptions and ASH membership may be found online at:
Copyright 2011 by The American Society of Hematology; all rights reserved.
Washington DC 20036.
by the American Society of Hematology, 2021 L St, NW, Suite 900,
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly
For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom For personal use only.by guest on September 22, 2013.bloodjournal.hematologylibrary.orgFrom
3. activates cellular proliferation through the activation of the NF-B
pathway and may induce BCL2 overexpression, promoting B-cell
survival, and lymphomagenesis.12-14
Molecular genetics
There are a number of well-defined genetic abnormalities in
HIV-associated lymphoma (Table 1). BL is associated with activa-
tion of the MYC gene and, when associated with HIV infection,
resembles sporadic rather than endemic BL.15 Interestingly, studies
have suggested that up to 20% of HIV-positive DLBCLs also
harbor a MYC translocation, and this raises the question of whether
some of these may be biologically closer to BLs, as recently
described in HIV-negative patients.16,17 BCL6 mutations are found
in 20% of centroblastic DLBCL and 60% of PEL lymphoma
cases.18-20 Finally, cytokine and chemokine dysregulation, such as
IL-6 and IL-10, are associated with EBV and HHV-8–associated
lymphomas and probably play an important and permissive role in
lymphomagenesis.2
Although in-depth gene-expression profiling of HIV-associated
lymphomas has not been performed, their molecular profiles are
probably similar to DLBCL and BL in HIV-negative patients.21
Early gene-expression profiling studies in untreated DLBCL identi-
fied distinct molecular subtypes with different oncogenic abnormali-
ties.22 Genes associated with germinal center B-cell (GCB) DL-
BCL included markers of germinal center differentiation, such as
CD10 and BCL6, whereas those associated with activated B-cell
like (ABC) DLBCL included IRF4/MUM1.23-25 A noteworthy
feature of ABC DLBCL was the very high expression of BCL2:
ABC DLBCL had more than 4-fold higher expression than GCB
DLBCL.22,26 These results suggested that the GCB and ABC
DLBCL subtypes are derived from B cells at different stages of
differentiation, with GCB DLBCL arising from germinal center
B cells and ABC DLBCL from post–germinal center B cells
blocked during plasmacytic differentiation.
Genetic analysis has revealed ABC and GCB DLBCL to be
pathogenetically distinct. GCB DLBCL is exclusively associated
with 2 recurrent oncogenic events: the t(14;18) translocation
involving the BCL2 gene and the immunoglobulin heavy chain
gene and amplification of the c-rel locus on chromosome 2p. They
also have amplification of the oncogenic mir-17-92 microRNA
cluster, deletion of the tumor suppressor PTEN, and frequent
abnormalities of BCL6.27,28 ABC DLBCLs have frequent amplifica-
tion of the oncogene SPIB, deletion of the INK4a/ARF tumor
suppressor locus and trisomy 3, and constitutive activation of the
NF-B pathway, in most cases.29-31 This has been linked to
abnormalities in several upstream proteins, including CARD11,
BCL10, and A20, leading to activation of IB kinase and NF-B.27,30
BL can be readily distinguished from DLBCL by the high level
of expression of MYC target genes, the expression of a subgroup of
germinal center B-cell genes, and the low level of expression of
MHC class I genes and NF-B target genes.16,17 Afew small studies
that have looked at gene expression profiling of PEL found its
profile to be similar to the non-GCB type of DLBCL and probably
of plasmablastic derivation.32,33
Diagnosis and evaluation
The most important diagnostic test is an adequate and properly
evaluated biopsy; in general, excisional biopsies should be per-
formed and core or fine needle aspiration biopsies are for the most
part inadequate. The tissue evaluation should be performed by an
experienced hematopathologist. Whereas many of these lympho-
mas will be histologically similar to those that develop in HIV-
negative patients, others, such as PEL and plasmablastic lym-
phoma, are observed mostly in HIV-infected patients.
Histology
HIV-associated DLBCL is divided into centroblastic and immuno-
blastic variants. The centroblastic type is characterized by diffuse
sheets of large lymphoid cells with round or oval nuclei and
prominent nucleoli. They often express germinal center-associated
markers, such as CD10 and BCL6, and are typically CD20
positive2,15,34 (Figure 1). The immunoblasic variant refers to those
cases containing more than 90% immunoblasts and often exhibits
features of plasmacytoid differentiation that may confound the
distinction from plasmablastic lymphomas.2,35,36 These tumors are
CD10-negative, being of post–germinal center derivation, and
frequently positive for MUM1/IRF4 and CD138/syndecan-1, mark-
ers associated with plasma cell derivation.15 These tumors have
Table 1. Viral and genetic abnormalities in human immunodeficiency virus (HIV)–associated lymphomas
3246 DUNLEAVY and WILSON BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
4. frequent mitoses with high Ki-67/MIB-1 scores.37 The centroblas-
tic type represents approximately 25% of HIV-associated lympho-
mas, whereas the immunoblastic type represents approximately
10%. In immunoblastic lymphoma, tumor cells may lose CD20
expression because of coexpression of EBV. Markers associated
with activation, such as CD30, CD38, and CD71, are often
expressed in immunoblastic types.2,5
The neoplastic cells in PEL range in appearance from large
immunoblastic to anaplastic large cell lymphoma-type cells. Al-
though this tumor is of B-cell origin, surface B-cell antigens, such
as CD20 and CD79a, are not expressed. CD45, CD30, CD38, and
CD138 are usually expressed and as discussed earlier are associ-
ated with KSHV/HHV-8 and EBV sometimes.33 Finally, plasmab-
lastic lymphomas, which typically occur in the oral cavity or jaw,
are usually positive for CD38, CD138, and MUM1/IRF4 and
negative for CD20 and CD45.36 EBV is present in greater than 50%
of cases, and these tumors appear to have biologic overlap with
PEL.33,38
HIV-associated BL is divided into 3 separate entities2: The
classic type accounts for approximately 30% of all HIV-associated
lymphomas and morphologically resembles classic BL encoun-
tered in HIV-negative patients. BL with plasmacytoid differentia-
tion is characterized by medium-sized cells with abundant cyto-
plasm and is much more commonly seen in the setting of immune
deficiency. Other cases show greater nuclear pleomorphism with
fewer but more prominent nuclei; and in the past, these were
referred to as “atypical” BL. All types have very high mitotic rates
with expression of CD19, CD20, CD79a, and CD10 and are
negative for BCL2. EBV positivity ranges from 30% in classic BL
to 50% to 70% in BL associated with plasmacytoid
differentiaton.6,9,39
Classic HL in the setting of HIV is mostly the mixed cellularity
subtype, and EBV is positive in virtually all cases.40 Interestingly,
in the CART era, there has been a significant increase in nodular
sclerosis HL because of a higher proportion of patients in higher
CD4 strata.33,41
Although gene-expression profiling is not routinely used in the
diagnosis of HIV-associated lymphoma, the cell of origin of
DLBCL (GCB or non-GCB) can be reasonably predicted by the
expression of 3 surface proteins (CD10, BCL6, and MUM1) on the
tumor tissue using immunohistochemistry as described in the Hans
algorithm.42 A recent algorithm from Choi incorporates 2 addi-
tional antibodies specific to GCB cells (GCET1 and FOXP1) and
may improve the predictive accuracy of immunohistochemistry.43
Although the cell of origin appears to be an independent predictor
of prognosis, with the ABC subtype (non-GCB) having a worse
outcome, both subtypes are treated similarly at present. However, a
recent study suggested that bortezomib may improve the outcome
of doxorubicin-based treatment of ABC DLBCL and this is being
studied in prospective studies.44,45 One diagnostic challenge is
identifying MYCϩ DLBCL because, like BL, these tumors have a
poor outcome with R-CHOP-based treatment.16,17 Thus, it is
prudent to perform cytogenetics or FISH for MYC translocations.
Evaluation
Patients should have a comprehensive medical history with atten-
tion paid to signs and symptoms of lymphoma, and a detailed HIV
history, including prior opportunistic infections and history of HIV
resistance, immune function, HIV viral control, and antiretroviral
treatment. The physical examination should include a careful
assessment of lymph node regions, the liver, and spleen. Relevant
laboratory studies include a complete blood count, chemistry
profile with lactate dehydrogenase and uric acid levels, CD4 cell
count, and HIV viral load. Hepatitis B and C serologies should be
assessed. A bone marrow aspirate and biopsy should be performed
at initial diagnosis as involvement by lymphoma is found in up to
20% of cases. Patients with aggressive B-cell lymphomas should
have a lumbar puncture for analysis of cerebrospinal fluid by flow
cytometry and cytology to check for leptomeningeal lymphoma.46
Imaging studies should include CT scanning of the chest,
abdomen and pelvis. Radiographic evaluation of the head should
also be performed preferably by MRI. Fluoro-deoxyglucose
positron emission tomography (FDG-PET) is useful in HIV-
negative aggressive lymphomas, but its role in HIV-associated
lymphomas is very poorly studied at this point in time. One of
Figure 1. A model for the histogenesis of HIV-associated lymphomas showing molecular and viral pathogenesis and DLBCL taxonomy. BL indicates Burkitt
lymphoma; DLBCL, diffuse large B-cell lymphoma; CB, centroblastic; IB, immunoblastic; PEL, primary effusion lymphoma; and PB, plasmablastic lymphoma.
HIV-ASSOCIATED LYMPHOMA 3247BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
5. the greatest limitations in using PET is that interpretation can be
confounded by inflammation from HIV-associated nodal reac-
tive hyperplasia, lipodystrophy, and infections.47,48 Prior experi-
ence evaluating FDG-PET in HIV-associated lymphoma is
limited to small retrospective series where most scans were not
predictive of remission.
The International Prognostic Index (IPI) is the standard prognos-
tic assessment tool in HIV-negative DLBCL. Its applicability to
HIV-associated DLBCL, however, is controversial. Whereas in
some studies using CHOP or R-CHOP, the IPI score has divided
groups prognostically, this has not been the case with DA-EPOCH
and in a recent study of short course-EPOCH-R (infusional
etoposide, vincristine, and doxorubicin with prednisone, cyclophos-
phamide, and rituximab) in newly diagnosed HIV-associated
DLBCL, the IPI did not predict progression-free survival (PFS) or
overall survival (OS).45,49,50 The prognostic importance of CD4 cell
count and immune function in HIV-associated DLBCL, neither of
which is part of the IPI, is the most likely confounding variable.
Patients with CD4 counts less than 100 cells/L are at increased
risk of serious opportunistic infections and death. Furthermore, as
noted earlier, patients with severe immune suppression have a
higher incidence of immunoblastic subtypes, most of which are of
ABC derivation, and a poor outcome compared with patients with
preserved immunity, where the GCB subtype is more common.48
Although a recently reported study from the AIDS Malignancy
Consortium (AMC) did not find an association between the cell of
origin and outcome in HIV-associated DLBCL, their analysis was
retrospective and included patients treated with a variety of
different regimens.51-53 Involvement of the CNS, which is in-
creased in HIV-associated aggressive B-cell lymphomas, also
confers an adverse prognosis.
Therapeutic controversies
The treatment of HIV-associated lymphoma has evolved over the
past 30 years in line with improved control of HIV replication and
preservation of immune function (Table 2). Over this period, the
therapeutic questions were driven by the need to balance the
administration of effective cytotoxic treatment with its effect on
immune function and infectious complications: (1) Should lower
doses of chemotherapy be used to reduce toxicity and immune
suppression? (2) What is the role of rituximab and the optimal
regimen? (3) Should CART be suspended during lymphoma
therapy?
Dose intensity
In the pre-CART era, patients with HIV-associated lymphoma had
poor outcomes with median survivals of 5 to 6 months. Because
these outcomes were driven by both chemotherapy failure and
infections, investigators have examined the effect of chemotherapy
dose on survival. In one study, Kaplan et al observed that higher
doses of cyclophosphamide were associated with lower survival,
suggesting that infections were a driving cause of death in these
patients.54 In an attempt to reduce infectious deaths, the AMC
conducted a study of 192 untreated lymphoma patients randomly
Table 2. Pivotal trials in HIV-associated lymphomas
3248 DUNLEAVY and WILSON BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
6. assigned to receive standard-dose m-BACOD (methotrexate, bleo-
mycin, doxorubicin, cyclophosphamide, vincristine, and dexameth-
asone) with GM-CSF support or low-dose mBACOD without
GM-CSF in an effort to reduce the toxicity of chemotherapy.55
Compared with full-dose therapy, reduced-dose treatment had a
similar response rate (52% vs 41%, respectively) and median
survival (6.8 vs 7.7 months, respectively) but lower hematologic
toxicity. This led the authors to conclude that lower-dose chemo-
therapy was preferable in HIV-associated lymphoma. One shortcom-
ing of the study was that, although the authors controlled for the
absolute CD4 cell count in the survival analysis, they did not
include enough patients with high CD4 counts and, ultimately,
could not support a definitive recommendation for this group where
the benefit of full-dose chemotherapy on cure of the lymphoma
may outweigh the infectious risks.37 In addition, in the post-CART
era, the proportion of patients with higher CD4 counts is much
larger. Importantly, before completion of this trial, a randomized
multicenter study in HIV-negative aggressive lymphoma showed
CHOP to be equally effective as mBACOD and less toxic.56 The
better therapeutic index of CHOP led to its acceptance as a standard
for HIV-associated lymphoma.57
Outcome in the CART era and the role of rituximab
The introduction of CART approximately 15 years ago has had a
dramatic effect on the outcome of HIV-associated lymphomas
with increases in median survival. Although the reasons are
multifactorial, they can be ultimately attributed to salutary effects
of CART on immune function. Patients with preserved immune
function have a lower risk of infectious complications, thereby
enabling optimal chemotherapy administration, and as noted
earlier, a more favorable tumor biology.5,37 Interestingly, in one
study that looked at risk-adapted intensive chemotherapy in 485
patients with AIDS-related lymphoma, CART was significantly
associated with survival, whereas the dose-intensity of CHOP-
based therapy was not.58
Although the benefit of rituximab is well established in
HIV-negative DLBCL, its role in HIV-associated DLBCL has been
controversial.59 This debate stems from an AMC randomized phase
3 study of CHOP with or without rituximab in HIV-associated
aggressive lymphomas that found rituximab was associated with
significantly more infectious deaths but only a trend in improved
tumor control; based on this, the authors concluded that rituximab
does not improve the clinical outcome of HIV-associated DLBCL.50
A retrospective analysis of 3 phase 2 trials from Italy, where
patients received infusional cyclophosphamide, doxorubicin and
etoposide (CDE) with rituximab, also concluded that rituximab
might increase infections.60,61 On closer evaluation of the AMC
trial, however, the increased infectious deaths occurred primarily in
patients with very low CD4 counts, and many patients received
“maintenance” rituximab after chemotherapy, which has not been
shown to be useful in HIV-negative DLBCL.62 Nonetheless, these
shortcomings confound any interpretation that rituximab is not
useful in HIV-associated DLBCL.
Subsequent to the AMC study, a French group performed a
phase 2 study of CHOP plus rituximab in HIV-associated NHL, and
the CR rate of 77% and 2 year-survival rate of 75% suggested that
rituximab was beneficial and could be given safely to this group of
patients.63 To further address the controversy of rituximab, the
AMC performed another randomized phase 2 study. At the time
that this study was designed, the results of the EPOCH regimen in
this population were very promising, and they randomized patients
to receive concurrent versus sequential rituximab with EPOCH
(etoposide, prednisone, vincristine, cyclophosphamide, and hy-
droxydaunorubicin).37,51 Importantly, they found that concurrent
rituximab was not associated with increased infectious deaths.37,51
The study also examined whether the complete response rate with
EPOCH-R was superior to CHOP with or without rituximab, using
a predetermined retrospective analysis, and whether concurrent
versus sequential rituximab was more toxic and/or more effective.
There was no difference in toxicity between the arms and the
authors rejected the null hypothesis of 50% (associated with CHOP
with or without rituximab) in favor of 75% complete response for
EPOCH with concurrent rituximab (P ϭ .005; power 0.89).51
Based on this study, we consider it very unwise to omit rituximab
from upfront therapy in HIV-associated lymphoma.
The results of the aforementioned AMC trial and our own
findings with EPOCH-based treatment in HIV-associated lympho-
mas suggest that it may be an optimal treatment regimen.37,47
Although one group demonstrated good efficacy with R-CHOP in a
multicenter setting, it is concerning that 15% of enrolled patients
were not evaluable for response because of early events or lacking
clinical and radiologic evaluations.63 Although the AMC’s conclu-
sions regarding EPOCH-R’s superiority over R-CHOP are based on
a historical comparison, the dramatic differential outcome with
these 2 regimens in a similar patient population suggests to us that
EPOCH-R is a better regimen in this population. Whether or not
there are subgroups of patients with HIV-associated DLBCL who
may do as well with R-CHOP is unknown at this time, and we
therefore recommend using EPOCH-R in all patients with HIV-
associated agressive lymphoma.
Our current strategy involves a second-generation EPOCH
regimen termed Short Course-EPOCH-RR (Figure 2), which is
based on the good efficacy and tolerability of DA-EPOCH in this
patient population.47 This approach is designed to address the dual
challenge of achieving excellent tumor control while preserving
immune integrity. Whereas we previously demonstrated that 6 cycles
of DA-EPOCH is highly effective (PFS and OS of 73% and 60%,
respectively, at 53 months) in HIV-associated lymphoma, we
hypothesized that the addition of rituximab would enhance efficacy
and allow a significant reduction in treatment cycles.37 With 5 years
of follow-up, the PFS and OS of SC-EPOCH-RR are 84% and
68%, respectively, and 79% of patients only required 3 treatment
cycles.47 In our study, PFS included patients who relapsed or were
refractory or died from lymphoma but HIV-related deaths were
censored.
To determine how many cycles of SC-EPOCH-RR are
needed, we use the paradigm shown in Figure 3. All patients
undergo restaging with CT and FDG-PET scan after the second
treatment cycle and each cycle thereafter until achieving a CR or
no further tumor shrinkage. The criteria for stopping treatment
is when, after a minimum of 3 cycles of therapy, there is less
than 25% reduction in bidimensional products compared with
the previous interim CT scan and the standardized uptake values
on FDG-PET have decreased by at least 50% compared with the
pretreatment FDG-PET. All patients receive at least 3 cycles of
therapy. Our liberal definition of required standardized uptake
value reduction was necessary to take into account HIV-
associated reactive changes that confound FDG-PET interpreta-
tion in HIV-positive patients.
We also required that all patients receive intrathecal therapy for
prophylaxis of CNS lymphoma; patients receive 12 mg of metho-
trexate intrathecally on days 1 and 5 of cycle 3, and this is repeated
every 3 weeks for a total of 6 doses (ie, cycles 3-5). If patients have
active leptomeningeal disease at diagnosis, detected by cytology or
HIV-ASSOCIATED LYMPHOMA 3249BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
7. flow cytometry, they receive induction intrathecal or intraventricu-
lar methotrexate twice weekly for 2 weeks beyond negative flow
cytometry (for a minimum of 4 weeks), followed by consolidation
weekly for 6 weeks and maintenance monthly for 6 months.46 All
patients also receive prophylaxis for Pneumocystis jiroveci and for
Mycobacterium avium if the CD4 count at lymphoma diagnosis is
less than 100/L.
Interestingly, with this approach, the clinical prognostic charac-
teristics that make up the IPI and the IPI itself do not predict PFS or
OS. Only tumor histogenesis is associated with lymphoma-specific
outcome with 95% of GCB versus 44% of non-GCB DLBCL
progression-free at 5 years. Although both EBV positivity of the
tumor and low CD4 count at diagnosis are significantly associated
with an inferior OS, they are not associated with lymphoma-
specific outcome (Figure 4).
Role of CART during therapy
The risks and benefits of continuing CART during curative
chemotherapy of aggressive lymphomas have been variably inter-
preted. Although many investigators rightly raise the concern that
uncontrolled HIV replication during chemotherapy will worsen
immune function, they often do not consider the potentially adverse
effects of CART on lymphoma-specific outcomes because they are
difficult to quantify. One of the first trials to assess concurrent
CART was a nonrandomized AMC study of dose reduced and
standard dose CHOP.64 A potentially important finding of the study
comes from the pharmacokinetic analysis, which showed that
cyclophosphamide clearance was reduced 1.5-fold but doxorubicin
clearance was unchanged compared with historical results. Al-
though it is reassuring that the doxorubicin pharmacokinetics were
Figure 2. SC-EPOCH-RR drug doses and schedule.
SC-EPOCH-RR is administered through a central line.
Patients have a complete blood count twice weekly and
at least 3 days apart. Cyclophosphamide is reduced 25%
for a nadir absolute neutrophil count (ANC) less than
0.5 ϫ 109/L (500/mm3) or platelet count less than
25.0 ϫ 109/L (25 000/mm3) lasting 2 to 4 days and 50% if
the nadir ANC was less than 0.5 ϫ 109/L (500/mm3) or
platelet count less than 25.0 ϫ 109/L (25 000/mm3) last-
ing for 5 or more days, based on twice weekly blood
counts.
Figure 3. SC-EPOCH-RR treatment paradigm. Pa-
tients receive 2 cycles of SC-EPOCH-RR and are then
restaged by CT and FDG-PET scanning. Patients in CR
after 2 cycles receive one more cycle (minimum 3) of
therapy. Patients with a “positive” CT and/or FDG-PET
study after 2 cycles receive additional cycles until they
were negative, for a maximum of 6 cycles.
3250 DUNLEAVY and WILSON BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
8. unaffected, the reduced clearance of cyclophosphamide, an inac-
tive prodrug, could probably result in a reduction of active
metabolites and potentially compromise efficacy. In this study,
CD4 counts increased significantly during therapy, and the mecha-
nism for increased CD4 cell counts raises the concern that CART
protects T cells from chemotherapy-induced cytotoxic stress, an
effect that might occur in the lymphoma cells.65,66 Although other
groups have suggested that CART can be safely administered with
chemotherapy, it has not been well prospectively studied and
controversies abound.67,68 In that respect, it is important to note that
many newer antiretrovirals with fewer drug interactions (than those
studied in the past) are now available.
Our approach has been to suspend CART during chemotherapy
because we think the risk-benefit of CART is not favorable. We are
particularly concerned with pharmacokinetic and pharmacody-
namic interactions that could lead to lower steady-state drug
concentrations, a particular problem with infusional regimens,
and/or increase toxicity, which may lead to chemotherapy dose
reductions.69,70 Of theoretical but no less important concern is the
potential inhibitory effect of some antiretroviral drug classes on
lymphoid cell apoptosis and the potential for CART noncompli-
ance, which would increase the risk of developing new HIV
mutations.71,72 To assess the risks of CART suspension, we
performed 2 prospective studies where CART was suspended
during chemotherapy (DA-EPOCH and SC-EPOCH-RR) and did
not observe a significant increased risk of infections during
therapy.37,47 Although the HIV viral loads rapidly increased and
then plateaued after the first cycle and the CD4 cells decreased over
the course of chemotherapy, both HIV viral loads and CD4 levels
returned to baseline levels a few months after the completion.37,47
Furthermore, there was loss of HIV-viral mutations, which were
present before treatment, after completion of EPOCH. Thus, our
current approach with SC-EPOCH-RR is to suspend CART from
the beginning until the completion of treatment and as 79% of
patients require just 3 cycles of therapy, the duration of CART
suspension is approximately 7 weeks, in the majority of cases
(Figure 3).
HIV-associated BL
Although, after the advent of CART, there was a significant
improvement in the outcome of HIV-associated DLBCL, this was
not the case initially with HIV-associated BL, as reported in a
retrospective series by Lim et al.73 This lack of improvement is
Figure 4. PFS and OS Kaplan-Meier curves. PFS (A) is
84% and OS (B) is 68% at the median follow-up of
5 years. PFS (C) and OS (D) for patients with GCB
versus non-GCB DLBCL. PFS (E) and OS (F) for EBV-
negative versus EBV-positive DLBCL, and PFS (G) and
OS (H) for CD4 cell count greater than 100 cells/L
(100 cells/mm3) versus less than 100 cells/L (100 cells/
mm3) at diagnosis.
HIV-ASSOCIATED LYMPHOMA 3251BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
9. probably explained by the widespread use of CHOP-based regi-
mens, which have poor efficacy in BL.16,74 Whereas dose-intense
regimens, such as hyper-CVAD (hyperfractionated cyclophosph-
amide, vincristine, doxorubicin, and dexamethasone) and CODOX-
M-IVAC, with or without rituximab, have shown encouraging
results in HIV-negative BL, they have not been studied too
extensively in HIV-associated BL. One of the concerns with
CODOX-M-IVAC is treatment-related toxicity in this popula-
tion.75,76 In an attempt to reduce this, the AMC recently presented
the results of a feasibility and toxicity study for HIV-associated BL
and atypical BL and reported good OS rates with 65% of patients
completing treatment as per protocol.77
BL highlights the necessity to balance treatment efficacy and
toxicity by optimizing the therapeutic index, especially in patients
who are immune-suppressed and/or elderly. In this regard, we
studied using DA-EPOCH-R in untreated BL based on its excellent
activity in highly proliferative DLBCL and its favorable toxicity
profile. Among 29 patients (including 10 HIV-positive treated with
SC-EPOCH-RR), we observed a complete remission and OS rate
of 100% at a median follow-up time of 57 months. The AMC also
included several patients with BL or Burkitt-like lymphoma in their
study of concurrent versus sequential EPOCH-R and reported high
response rates in this group.51 In summary, although modified
CODOX-M-IVAC regimens are effective and reasonably well
tolerated in this population, our current approach is to use
SC-EPOCH-RR for newly diagnosed patients with HIV-associated
BL (Figure 2). The treatment paradigm that we use is the same as
for DLBCL, with the majority of patients requiring only 3 cycles of
therapy and short duration of CART suspension (Figure 3).47 All
patients receive prophylactic intrathecal therapy, and those with
leptomeningeal disease at diagnosis receive intensive intrathecal
therapy for at least 6 months’ duration.47 A prospective national
study that will test the regimen in both HIV-negative and HIV-
positive patients with BL is planned at this time.
Approaches to other HIV-associated
lymphomas
HL
In the setting of HIV infection, classic HL occurs most frequently
in patients with depressed immune function. However, a paradoxi-
cal increase in classic HL has been observed in the CART era
despite an overall improvement in immune function in most
patients.78 This is probably explained by examining the incidence
of the 2 major subtypes of classic HL that occur in HIV infection. In
the pre-CART era, most classic HL was mixed cellularity subtype,
which is EBV-positive and occurs mostly in immune-suppressed
patients, whereas more recently there has been an increased
incidence of nodular sclerosis HL, which occurs more commonly at
higher CD4 counts.41 When considering treatment, one needs to
consider that patients with the mixed cellularity subtype typically
have advanced disease, including bone marrow involvement, and
require chemotherapy alone. In contrast, patients with nodular
sclerosis HL will typically present with mediastinal masses and
may benefit from combined modality treatment in selected cases.
No studies have adequately evaluated different regimens in HIV-
associated HL to make definitive recommendations about regimen
efficacy. Thus, we recommend doxorubicin, bleomycin, vinblas-
tine, and dacarbazine (ABVD) chemotherapy, which is the standard
for HIV-negative patients. The impact of CART suspension has not
been well studied in HL, but given the relatively long treatment
duration and bolus scheduling of ABVD, we recommend that
CART be continued.
PCNSL
Primary central nervous system lymphoma (PCNSL) typically
presents in patients with severe immune suppression. Thus, it is not
unexpected that since the advent of CART, its incidence has
decreased dramatically. Although the disease remains incurable in
most patients, the duration of survival appears to have increased.
Compared with HIV-negative patients, HIV-associated PCNSL is
typically EBV-positive.2 Patients frequently present with changes
in mental status or focal neurologic symptoms and, unlike HIV-
negative PCNSL, they tend to present with multiple brain lesions.
Because these patients are severely immune-suppressed, intracra-
nial opportunistic infections should always be considered in the
differential diagnosis when evaluating intracranial lesions on
imaging studies.
Unlike HIV-negative PCNSL, where high-dose methotrexate
and, more recently, combination chemotherapy regimens are
effective, total brain irradiation remains standard in HIV-associated
PCNSL. Whereas most studies in the pre-CART era report a
median survival in the range of 3 months, survival more than
1.5 years has been reported in patients who respond to CART and
were treated with radiation.79,80 The role of systemic therapy and
rituximab remains undefined in this disease, although some studies
are investigating these agents. Our approach is to recommend that
these patients be referred for investigational studies or, if unavail-
able, total brain radiation is reasonable.
PEL and plasmablastic lymphoma
The outcome of PEL is poor with standard treatment and the
median survival is in the range of 6 months.81 Unlike some other
HIV-associated lymphomas, CART does not appear to have had a
significant impact on survival. At this time, the optimal therapy for
PEL remains to be defined, but regimens such as EPOCH and CDE
may be beneficial. Other approaches, such as high-dose methotrex-
ate and parenteral zidovudine with interferon-␣, have been studied
but have demonstrated limited efficacy.82,83 The prognosis of
plasmablastic lymphoma in the setting of HIV has also been
historically poor.38,84 The impact of CART has not been well
studied but anecdotal reports suggest its prognosis may have
improved since the introduction of CART.85 It is reasonable to
consider regimens, such as EPOCH or CDE, for this disease.
Newer agents, such as bortezomib and lenalidomide, have been
used anecdotally with some reports of activity and success.86
Relapsed lymphoma
Relapsed lymphoma is associated with a poor prognosis, and
median survivals tend to be less than 1 year. A recent Italian study
prospectively evaluated high-dose therapy and stem cell transplan-
tation in 50 patients with relapsed HIV-associated lymphoma (both
HL and NHL).87 Whereas the median OS of patients was 33 months,
patients who had chemo-sensitive disease had a relatively favor-
able outcome and were disease free at 44 months of follow-up.
Given the significant improvements in HIV control and immune
function, it is reasonable to approach relapsed HIV- associated
lymphomas similarly to their HIV-negative counterparts and to
pursue aggressive strategies if appropriate. Less aggressive strate-
gies, such as etoposide, solumedrol, high-dose cytarabine, and
3252 DUNLEAVY and WILSON BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
10. platinum and CDE, have poor outcomes.61,88 The role of allogeneic
transplantation has not been well evaluated at this time.
Future directions
Our approach to treating HIV-associated DLBCL and BL is to use
EPOCH-R (with antiretroviral therapy suspension), and prelimi-
nary evidence from our institution suggests that abbreviated cycles
may be given to further reduce toxicity. For HL, we use ABVD
with antiretroviral continuation because of the long duration of
therapy. For PCNSL and less common HIV-associated lymphomas,
survival with standard approaches to date has been poor and
experimental therapy should be considered.
The outcome of HIV-associated lymphoma has undergone
significant improvement in recent years beginning with the wide-
spread use of CART. Both DLBCL and BL are highly curable
diseases for the most part. To further improve the outcome of these
lymphomas, the challenge is to identify driver pathways and
therapeutic targets. In this regard, we are investigating modulation
of the B-cell receptor cascade and NFB transcription factor, which
are involved in the pathobiology of ABC DLBCL.44,89 For GCB
DLBCL and BL, current approaches have excellent efficacy with
little room for improvement so that future studies should focus on
further reducing treatment toxicity, particularly in highly immune-
suppressed patients. Advances in the therapeutics of poor prognos-
tic diseases, such as HIV-associated PCNSL and PEL, which are
now much more rarely encountered, will probably come from
improved understanding of their pathobiology.
Acknowledgments
This work was supported by the Intramural Research Program of
the National Cancer Institute of the National Institutes of Health.
Authorship
Contribution: K.D. and W.H.W. wrote and gave final approval of
the manuscript.
Conflict-of-interest disclosure: The authors declare no compet-
ing financial interests.
Correspondence: Kieron Dunleavy, Metabolism Branch, Na-
tional Cancer Institute, Bldg 10, Rm 4N-115, 9000 Rockville Pike,
Bethesda, MD 20892; e-mail: dunleavk@mail.nih.gov.
References
1. Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-
associated non-Hodgkin lymphoma. Lancet.
1991;337(8745):805-809.
2. Swerdlow SH, Campo E, Harris NL, et al. WHO
Classification of Tumours of Haematopoietic and
Lymphoid Tissues. Lyon, France: IARC; 2008.
3. Besson C, Goubar A, Gabarre J, et al. Changes
in AIDS-related lymphoma since the era of highly
active antiretroviral therapy. Blood. 2001;98(8):
2339-2344.
4. Little RF, Wilson WH. Update on the pathogene-
sis, diagnosis, and therapy of AIDS-related lym-
phoma. Curr Infect Dis Rep. 2003;5(2):176-184.
5. Carbone A, Gloghini A. AIDS-related lymphomas:
from pathogenesis to pathology. Br J Haematol.
2005;130(5):662-670.
6. Raphael MM, Audouin J, Lamine M, et al. Immu-
nophenotypic and genotypic analysis of acquired
immunodeficiency syndrome-related non-
Hodgkin’s lymphomas: correlation with histologic
features in 36 cases. French Study Group of Pa-
thology for HIV-Associated Tumors. Am J Clin
Pathol. 1994;101(6):773-782.
7. Landgren O, Goedert JJ, Rabkin CS, et al. Circu-
lating serum free light chains as predictive mark-
ers of AIDS-related lymphoma. J Clin Oncol.
2010;28(5):773-779.
8. Nador RG, Cesarman E, Chadburn A, et al. Pri-
mary effusion lymphoma: a distinct clinicopatho-
logic entity associated with the Kaposi’s sarcoma-
associated herpes virus. Blood. 1996;88(2):645-
656.
9. Davi F, Delecluse HJ, Guiet P, et al. Burkitt-like
lymphomas in AIDS patients: characterization
within a series of 103 human immunodeficiency
virus-associated non-Hodgkin’s lymphomas.
Burkitt’s Lymphoma Study Group. J Clin Oncol.
1998;16(12):3788-3795.
10. Ambinder RF. Epstein-Barr virus associated lym-
phoproliferations in the AIDS setting. Eur J Can-
cer. 2001;37(10):1209-1216.
11. Carbone A, Tirelli U, Gloghini A, Volpe R,
Boiocchi M. Human immunodeficiency virus-
associated systemic lymphomas may be subdi-
vided into two main groups according to Epstein-
Barr viral latent gene expression. J Clin Oncol.
1993;11(9):1674-1681.
12. Gaidano G, Capello D, Carbone A. The molecular
basis of acquired immunodeficiency syndrome-
related lymphomagenesis. Semin Oncol. 2000;
27(4):431-441.
13. Henderson S, Rowe M, Gregory C, et al. Induc-
tion of bcl-2 expression by Epstein-Barr virus la-
tent membrane protein 1 protects infected B cells
from programmed cell death. Cell. 1991;65(7):
1107-1115.
14. Rothe M, Sarma V, Dixit VM, Goeddel DV.
TRAF2-mediated activation of NF-kappa B by
TNF receptor 2 and CD40. Science. 1995;
269(5229):1424-1427.
15. Carbone A. Emerging pathways in the develop-
ment of AIDS-related lymphomas. Lancet Oncol.
2003;4(1):22-29.
16. Dave SS, Fu K, Wright GW, et al. Molecular diag-
nosis of Burkitt’s lymphoma. N Engl J Med. 2006;
354(23):2431-2442.
17. Hummel M, Bentink S, Berger H, et al. A biologic
definition of Burkitt’s lymphoma from transcrip-
tional and genomic profiling. N Engl J Med. 2006;
354(23):2419-2430.
18. Gaidano G, Capello D, Cilia AM, et al. Genetic
characterization of HHV-8/KSHV-positive primary
effusion lymphoma reveals frequent mutations of
BCL6: implications for disease pathogenesis and
histogenesis. Genes Chromosomes Cancer.
1999;24(1):16-23.
19. Gaidano G, Carbone A, Pastore C, et al. Fre-
quent mutation of the 5Ј noncoding region of the
BCL-6 gene in acquired immunodeficiency syn-
drome-related non-Hodgkin’s lymphomas. Blood.
1997;89(10):3755-3762.
20. Gaidano G, Lo Coco F, Ye BH, et al. Rearrange-
ments of the BCL-6 gene in acquired immunode-
ficiency syndrome-associated non-Hodgkin’s lym-
phoma: association with diffuse large-cell
subtype. Blood. 1994;84(2):397-402.
21. Lenz G, Staudt LM. Aggressive lymphomas.
N Engl J Med. 2010;362(15):1417-1429.
22. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct
types of diffuse large B-cell lymphoma identified
by gene expression profiling. Nature. 2000;
403(6769):503-511.
23. Dalla-Favera R, Migliazza A, Chang CC, et al.
Molecular pathogenesis of B cell malignancy: the
role of BCL-6. Curr Top Microbiol Immunol. 1999;
246:257-263.
24. Matsuyama T, Grossman A, Mittrucker HW, et al.
Molecular cloning of LSIRF, a lymphoid-specific
member of the interferon regulatory factor family
that binds the interferon-stimulated response ele-
ment (ISRE). Nucleic Acids Res. 1995;23(12):
2127-2136.
25. Mittrucker HW, Matsuyama T, Grossman A, et al.
Requirement for the transcription factor LSIRF/
IRF4 for mature B and T lymphocyte function.
Science. 1997;275(5299):540-543.
26. Tschopp J, Irmler M, Thome M. Inhibition of fas
death signals by FLIPs. Curr Opin Immunol.
1998;10(5):552-558.
27. Lenz G, Wright GW, Emre NC, et al. Molecular
subtypes of diffuse large B-cell lymphoma arise
by distinct genetic pathways. Proc Natl Acad Sci
U S A. 2008;105(36):13520-13525.
28. Parekh S, Polo JM, Shaknovich R, et al. BCL6
programs lymphoma cells for survival and differ-
entiation through distinct biochemical mecha-
nisms. Blood. 2007;110(6):2067-2074.
29. Davis RE, Brown KD, Siebenlist U, Staudt LM.
Constitutive nuclear factor kappaB activity is re-
quired for survival of activated B cell-like diffuse
large B cell lymphoma cells. J Exp Med. 2001;
194(12):1861-1874.
30. Lenz G, Davis RE, Ngo VN, et al. Oncogenic
CARD11 mutations in human diffuse large B cell
lymphoma. Science. 2008;319(5870):1676-1679.
31. Ngo VN, Davis RE, Lamy L, et al.Aloss-of-function
RNAinterference screen for molecular targets in
cancer. Nature. 2006;441(7089):106-110.
32. Fan W, Bubman D, ChadburnA, Harrington WJ Jr,
Cesarman E, Knowles DM. Distinct subsets of
primary effusion lymphoma can be identified
based on their cellular gene expression profile
and viral association. J Virol. 2005;79(2):1244-
1251.
33. Klein U, Gloghini A, Gaidano G, et al. Gene ex-
pression profile analysis of AIDS-related primary
effusion lymphoma (PEL) suggests a plasmablas-
tic derivation and identifies PEL-specific tran-
scripts. Blood. 2003;101(10):4115-4121.
34. Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK.
HIV-ASSOCIATED LYMPHOMA 3253BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
11. World Health Organization classification of neo-
plastic diseases of the hematopoietic and lym-
phoid tissues: a progress report. Am J Clin
Pathol. 1999;111(1 suppl 1):S8-S12.
35. Colomo L, Loong F, Rives S, et al. Diffuse large
B-cell lymphomas with plasmablastic differentia-
tion represent a heterogeneous group of disease
entities. Am J Surg Pathol. 2004;28(6):736-747.
36. Vega F, Chang CC, Medeiros LJ, et al. Plasmab-
lastic lymphomas and plasmablastic plasma cell
myelomas have nearly identical immunopheno-
typic profiles. Mod Pathol. 2005;18(6):806-815.
37. Little RF, Pittaluga S, Grant N, et al. Highly effec-
tive treatment of acquired immunodeficiency syn-
drome-related lymphoma with dose-adjusted EP-
OCH: impact of antiretroviral therapy suspension
and tumor biology. Blood. 2003;101(12):4653-
4659.
38. Delecluse HJ, Anagnostopoulos I, Dallenbach F,
et al. Plasmablastic lymphomas of the oral cavity:
a new entity associated with the human immuno-
deficiency virus infection. Blood. 1997;89(4):
1413-1420.
39. Raphael M, Gentilhomme O, Tulliez M, Byron PA,
Diebold J. Histopathologic features of high-grade
non-Hodgkin’s lymphomas in acquired immuno-
deficiency syndrome: the French Study Group of
Pathology for Human Immunodeficiency Virus-
Associated Tumors. Arch Pathol Lab Med. 1991;
115(1):15-20.
40. Thompson LD, Fisher SI, Chu WS, Nelson A,
Abbondanzo SL. HIV-associated Hodgkin lym-
phoma: a clinicopathologic and immunopheno-
typic study of 45 cases. Am J Clin Pathol. 2004;
121(5):727-738.
41. Biggar RJ, Jaffe ES, Goedert JJ, Chaturvedi A,
Pfeiffer R, Engels EA. Hodgkin lymphoma and
immunodeficiency in persons with HIV/AIDS.
Blood. 2006;108(12):3786-3791.
42. Hans CP, Weisenburger DD, Greiner TC, et al.
Confirmation of the molecular classification of
diffuse large B-cell lymphoma by immunohisto-
chemistry using a tissue microarray. Blood. 2004;
103(1):275-282.
43. Choi WW, Weisenburger DD, Greiner TC, et al. A
new immunostain algorithm classifies diffuse
large B-cell lymphoma into molecular subtypes
with high accuracy. Clin Cancer Res. 2009;
15(17):5494-5502.
44. Dunleavy K, Pittaluga S, Czuczman MS, et al.
Differential efficacy of bortezomib plus chemo-
therapy within molecular subtypes of diffuse large
B-cell lymphoma. Blood. 2009;113(24):6069-
6076.
45. Ruan J, Martin P, Furman RR, et al. Bortezomib
plus CHOP-rituximab for previously untreated
diffuse large B-cell lymphoma and mantle cell
lymphoma. J Clin Oncol. 2011;29(6):690-697.
46. Hegde U, Filie A, Little RF, et al. High incidence of
occult leptomeningeal disease detected by flow
cytometry in newly diagnosed aggressive B-cell
lymphomas at risk for central nervous system in-
volvement: the role of flow cytometry versus cy-
tology. Blood. 2005;105(2):496-502.
47. Dunleavy K, Little RF, Pittaluga S, et al. The role
of tumor histogenesis, FDG-PET, and short-
course EPOCH with dose-dense rituximab (SC-
EPOCH-RR) in HIV-associated diffuse large
B-cell lymphoma. Blood. 2010;115(15):3017-
3024.
48. Dunleavy K, Mikhaeel G, Sehn LH, Hicks RJ,
Wilson WH. The value of positron emission to-
mography in prognosis and response assess-
ment in non-Hodgkin lymphoma. Leuk Lym-
phoma. 2010;51(suppl 1):28-33.
49. Ribera JM, Oriol A, Morgades M, et al. Safety and
efficacy of cyclophosphamide, adriamycin, vin-
cristine, prednisone and rituximab in patients with
human immunodeficiency virus-associated dif-
fuse large B-cell lymphoma: results of a phase II
trial. Br J Haematol. 2008;140(4):411-419.
50. Kaplan LD, Lee JY, Ambinder RF, et al. Rituximab
does not improve clinical outcome in a random-
ized phase 3 trial of CHOP with or without ritux-
imab in patients with HIV-associated non-
Hodgkin lymphoma: AIDS-Malignancies Consor-
tium Trial 010. Blood. 2005;106(5):1538-1543.
51. Sparano JA, Lee JY, Kaplan LD, et al. Rituximab
plus concurrent infusional EPOCH chemotherapy
is highly effective in HIV-associated B-cell non-
Hodgkin lymphoma. Blood. 2010;115(15):3008-
3016.
52. Chadburn A, Chiu A, Lee JY, et al. Immunopheno-
typic analysis of AIDS-related diffuse large B-cell
lymphoma and clinical implications in patients
from AIDS Malignancies Consortium clinical trials
010 and 034. J Clin Oncol. 2009;27(30):5039-
5048.
53. Dunleavy K, Wilson WH. Role of molecular sub-
type in predicting outcome of AIDS-related diffuse
large B-cell lymphoma. J Clin Oncol. 2010;
28(16):e260; author reply e261-e262.
54. Kaplan LD, Abrams DI, Feigal E, et al. AIDS-
associated non-Hodgkin’s lymphoma in San
Francisco. JAMA. 1989;261(5):719-724.
55. Kaplan LD, Straus DJ, Testa MA, et al. Low-dose
compared with standard-dose m-BACOD chemo-
therapy for non-Hodgkin’s lymphoma associated
with human immunodeficiency virus infection:
National Institute of Allergy and Infectious Dis-
eases AIDS Clinical Trials Group. N Engl J Med.
1997;336(23):1641-1648.
56. Fisher RI, Gaynor ER, Dahlberg S, et al. Com-
parison of a standard regimen (CHOP) with three
intensive chemotherapy regimens for advanced
non-Hodgkin’s lymphoma. N Engl J Med. 1993;
328(14):1002-1006.
57. Lim ST, Levine AM. Recent advances in acquired
immunodeficiency syndrome (AIDS)-related lym-
phoma. CA Cancer J Clin. 2005;55(4):229-241.
58. Mounier N, Spina M, Gabarre J, et al. AIDS-
related non-Hodgkin lymphoma: final analysis of
485 patients treated with risk-adapted intensive
chemotherapy. Blood. 2006;107(10):3832-3840.
59. Coiffier B, Lepage E, Briere J, et al. CHOP che-
motherapy plus rituximab compared with CHOP
alone in elderly patients with diffuse large-B-cell
lymphoma. N Engl J Med. 2002;346(4):235-242.
60. Spina M, Jaeger U, Sparano JA, et al. Rituximab
plus infusional cyclophosphamide, doxorubicin,
and etoposide in HIV-associated non-Hodgkin
lymphoma: pooled results from 3 phase 2 trials.
Blood. 2005;105(5):1891-1897.
61. Spina M, Vaccher E, Juzbasic S, et al. Human
immunodeficiency virus-related non-Hodgkin lym-
phoma: activity of infusional cyclophosphamide,
doxorubicin, and etoposide as second-line che-
motherapy in 40 patients. Cancer. 2001;92(1):
200-206.
62. Dunleavy K, Wilson WH, Kaplan LD. The case for
rituximab in AIDS-related lymphoma. Blood.
2006;107(7):3014-3015.
63. Boue F, Gabarre J, Gisselbrecht C, et al. Phase II
trial of CHOP plus rituximab in patients with HIV-
associated non-Hodgkin’s lymphoma. J Clin On-
col. 2006;24(25):4123-4128.
64. Ratner L, Lee J, Tang S, et al. Chemotherapy for
human immunodeficiency virus-associated non-
Hodgkin’s lymphoma in combination with highly
active antiretroviral therapy. J Clin Oncol. 2001;
19(8):2171-2178.
65. Johnson N, Parkin JM. Anti-retroviral therapy re-
verses HIV-associated abnormalities in lympho-
cyte apoptosis. Clin Exp Immunol. 1998;113(2):
229-234.
66. Phenix BN, Angel JB, Mandy F, et al. Decreased
HIV-associated T cell apoptosis by HIV protease
inhibitors. AIDS Res Hum Retroviruses. 2000;
16(6):559-567.
67. Sparano JA, Lee S, Chen MG, et al. Phase II trial
of infusional cyclophosphamide, doxorubicin, and
etoposide in patients with HIV-associated non-
Hodgkin’s lymphoma: an Eastern Cooperative
Oncology Group Trial (E1494). J Clin Oncol.
2004;22(8):1491-1500.
68. Vaccher E, Spina M, di Gennaro G, et al. Con-
comitant cyclophosphamide, doxorubicin, vincris-
tine, and prednisone chemotherapy plus highly
active antiretroviral therapy in patients with hu-
man immunodeficiency virus-related, non-
Hodgkin lymphoma. Cancer. 2001;91(1):155-163.
69. Tulpule A, Sherrod A, Dharmapala D, et al. Multi-
drug resistance (MDR-1) expression in AIDS-
related lymphomas. Leuk Res. 2002;26(2):121-
127.
70. Wilson WH, Bates SE, Fojo A, et al. Controlled
trial of dexverapamil, a modulator of multidrug
resistance, in lymphomas refractory to EPOCH
chemotherapy. J Clin Oncol. 1995;13(8):1995-
2004.
71. Phenix BN, Cooper C, Owen C, Badley AD.
Modulation of apoptosis by HIV protease inhibi-
tors. Apoptosis. 2002;7(4):295-312.
72. Phenix BN, Lum JJ, Nie Z, Sanchez-Dardon J,
Badley AD. Antiapoptotic mechanism of HIV pro-
tease inhibitors: preventing mitochondrial trans-
membrane potential loss. Blood. 2001;98(4):
1078-1085.
73. Lim ST, Karim R, Nathwani BN, Tulpule A,
Espina B, Levine AM. AIDS-related Burkitt’s lym-
phoma versus diffuse large-cell lymphoma in the
pre-highly active antiretroviral therapy (HAART)
and HAART eras: significant differences in sur-
vival with standard chemotherapy. J Clin Oncol.
2005;23(19):4430-4438.
74. Bishop PC, Rao VK, Wilson WH. Burkitt’s lym-
phoma: molecular pathogenesis and treatment.
Cancer Invest. 2000;18(6):574-583.
75. Barnes JA, Lacasce AS, Feng Y, et al. Evaluation
of the addition of rituximab to CODOX-M/IVAC for
Burkitt’s lymphoma: a retrospective analysis. Ann
Oncol. 2011;22(8):1859-1864.
76. Cortes J, Thomas D, Rios A, et al. Hyperfraction-
ated cyclophosphamide, vincristine, doxorubicin,
and dexamethasone and highly active antiretrovi-
ral therapy for patients with acquired immunodefi-
ciency syndrome-related Burkitt lymphoma/
leukemia. Cancer. 2002;94(5):1492-1499.
77. Noy A, Kaplan L, Lee J. Feasibility and toxicity of
a modified dose intensive R-CODOX-M/IVAC for
HIV-associated Burkitt and atypical Burkitt lym-
phoma (BL): preliminary results of a Prospective
Multicenter Phase II Trial of the AIDS Malignancy
Consortium (AMC) [abstract]. ASH Annual Meet-
ing Abstracts. 2009;114:3673.
78. Bohlius J, Schmidlin K, Boue F, et al. HIV-1-
related Hodgkin lymphoma in the era of combina-
tion antiretroviral therapy: incidence and evolu-
tion of CD4ϩ T-cell lymphocytes. Blood. 2011;
117(23):6100-6108.
79. Hoffmann C, Tabrizian S, Wolf E, et al. Survival of
AIDS patients with primary central nervous sys-
tem lymphoma is dramatically improved by
HAART-induced immune recovery. AIDS. 2001;
15(16):2119-2127.
80. Ling SM, Roach M 3rd, Larson DA, Wara WM.
Radiotherapy of primary central nervous system
lymphoma in patients with and without human
immunodeficiency virus: ten years of treatment
experience at the University of California San
Francisco. Cancer. 1994;73(10):2570-2582.
81. Boulanger E, Gerard L, Gabarre J, et al. Prognos-
tic factors and outcome of human herpesvirus
8-associated primary effusion lymphoma in pa-
tients with AIDS. J Clin Oncol. 2005;23(19):4372-
4380.
82. Boulanger E, Daniel MT,Agbalika F, Oksenhendler E.
Combined chemotherapy including high-dose
methotrexate in KSHV/HHV-8-associated primary
effusion lymphoma. Am J Hematol. 2003;73(3):
143-148.
83. Ghosh SK, Wood C, Boise LH, et al. Potentiation
of TRAIL-induced apoptosis in primary effusion
3254 DUNLEAVY and WILSON BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14
12. lymphoma through azidothymidine-mediated inhi-
bition of NF-kappa B. Blood. 2003;101(6):2321-
2327.
84. Castillo JJ, Winer ES, Stachurski D, et al. Clinical
and pathological differences between human im-
munodeficiency virus-positive and human immu-
nodeficiency virus-negative patients with plas-
mablastic lymphoma. Leuk Lymphoma. 2010;
51(11):2047-2053.
85. Lester R, Li C, Phillips P, et al. Improved outcome
of human immunodeficiency virus-associated
plasmablastic lymphoma of the oral cavity in the
era of highly active antiretroviral therapy: a report
of two cases. Leuk Lymphoma. 2004;45(9):1881-
1885.
86. Bibas M, Grisetti S, Alba L, Picchi G,
Del Nonno F, Antinori A. Patient with HIV-
associated plasmablastic lymphoma responding
to bortezomib alone and in combination with
dexamethasone, gemcitabine, oxaliplatin, cytara-
bine, and pegfilgrastim chemotherapy and lena-
lidomide alone. J Clin Oncol. 2010;28(34):e704-
e708.
87. Re A, Michieli M, Casari S, et al. High-dose
therapy and autologous peripheral blood stem
cell transplantation as salvage treatment for
AIDS-related lymphoma: long-term results of the
Italian Cooperative Group on AIDS and Tumors
(GICAT) study with analysis of prognostic factors.
Blood. 2009;114(7):1306-1313.
88. Bi J, Espina BM, Tulpule A, Boswell W,
Levine AM. High-dose cytosine-arabinoside and
cisplatin regimens as salvage therapy for refrac-
tory or relapsed AIDS-related non-Hodgkin’s lym-
phoma. J Acquir Immune Defic Syndr. 2001;
28(5):416-421.
89. Davis RE, Ngo VN, Lenz G, et al. Chronic ac-
tive B-cell-receptor signalling in diffuse large
B-cell lymphoma. Nature. 2010;463(7277):88-
92.
HIV-ASSOCIATED LYMPHOMA 3255BLOOD, 5 APRIL 2012 ⅐ VOLUME 119, NUMBER 14