Hematopoietic stem cell transplantation involves replacing a patient's abnormal or diseased hematopoietic system with healthy stem cells from a donor. It is used to treat both malignant and non-malignant hematological disorders. There are various sources of stem cells including bone marrow, peripheral blood, and umbilical cord blood. Complications after transplantation can include graft-versus-host disease, infections, and transplant-related toxicities. Close monitoring and management is required after transplantation to monitor engraftment and address any complications that may arise.
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
The collection and processing of hematopoieticakshaya tomar
BASICS OF HSC COLLECTION AND PROCESSING INCLUDING ALL THE THREE SOURCES, A BRIEF ABOUT STEM CELL MOBILIZATION, STEM CELL SELECTION CRYOPRESERVATION AND DMSO
In this presentation, I discuss a new standard of treatment in cancers which is immunotherapy. I also discuss the few cancers for which it has been approved.
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Cancer Immunotherapies (Focus on Melanoma & Lung Cancers)Zeena Nackerdien
Effective immunotherapy i.e. enlisting the patient’s own immune system to fight disease may mark a milestone in the fight against certain cancers. Three lymphocytes – T cells, B cells and NK-cells – involved in specific immune responses against cancers and other diseases. T cells recognize specific antigens via a T-cell antigen-receptor. The two main types of T cells, CD4- and CD8 T-cells, are categorized according to their respective CD4 and CD8 surface markers. The latter group includes cytotoxic T cells, also known as killer T lymphocytes. These cells kill invading pathogens or other disease-causing agents. Scientists discovered that a type of protein receptor, cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), prevented T cells from launching immune attacks [1]. In the early 1990s, another “brake” was discovered in dying T cells namely programmed death 1 or PD-1. The rationale underlying cancer immunotherapy is that exposing CTLA-4, PD-1 or using other appropriate immune-system-based therapies may enable the activation of the immune system to destroy cancer.
Genetically engineering a patient’s T cells to target tumor cells marked one of the promising turning points in cancer immunotherapy, particularly for certain blood cancers and solid tumors. Melanoma and lung cancer, two often-fatal diseases, are treatable in the early stages with surgery or other standards of care. However, some patients are diagnosed during the later stages of the disease or relapse with refractory/unresectable tumors. For these subgroups, the latest National Comprehensive Cancer Network (NCCN) tailored algorithms coupled with systemic treatment options, including immunotherapies, could potentially improve outcomes. Here, I summarize the latest approved immunotherapies mentioned in the NCCN guidelines, along with other examples of investigational agents such as monoclonal antibodies, cancer vaccines, and natural killer cells. Additional examples of targeted therapies, novel “druggable” and other immunotargets are presented in the section, ”Future Directions.”
Reference
1. Couzin-Frankel, J., Breakthrough of the year 2013. Cancer immunotherapy. Science, 2013. 342(6165): p. 1432-3.
The collection and processing of hematopoieticakshaya tomar
BASICS OF HSC COLLECTION AND PROCESSING INCLUDING ALL THE THREE SOURCES, A BRIEF ABOUT STEM CELL MOBILIZATION, STEM CELL SELECTION CRYOPRESERVATION AND DMSO
In this presentation, I discuss a new standard of treatment in cancers which is immunotherapy. I also discuss the few cancers for which it has been approved.
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Cancer Immunotherapies (Focus on Melanoma & Lung Cancers)Zeena Nackerdien
Effective immunotherapy i.e. enlisting the patient’s own immune system to fight disease may mark a milestone in the fight against certain cancers. Three lymphocytes – T cells, B cells and NK-cells – involved in specific immune responses against cancers and other diseases. T cells recognize specific antigens via a T-cell antigen-receptor. The two main types of T cells, CD4- and CD8 T-cells, are categorized according to their respective CD4 and CD8 surface markers. The latter group includes cytotoxic T cells, also known as killer T lymphocytes. These cells kill invading pathogens or other disease-causing agents. Scientists discovered that a type of protein receptor, cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), prevented T cells from launching immune attacks [1]. In the early 1990s, another “brake” was discovered in dying T cells namely programmed death 1 or PD-1. The rationale underlying cancer immunotherapy is that exposing CTLA-4, PD-1 or using other appropriate immune-system-based therapies may enable the activation of the immune system to destroy cancer.
Genetically engineering a patient’s T cells to target tumor cells marked one of the promising turning points in cancer immunotherapy, particularly for certain blood cancers and solid tumors. Melanoma and lung cancer, two often-fatal diseases, are treatable in the early stages with surgery or other standards of care. However, some patients are diagnosed during the later stages of the disease or relapse with refractory/unresectable tumors. For these subgroups, the latest National Comprehensive Cancer Network (NCCN) tailored algorithms coupled with systemic treatment options, including immunotherapies, could potentially improve outcomes. Here, I summarize the latest approved immunotherapies mentioned in the NCCN guidelines, along with other examples of investigational agents such as monoclonal antibodies, cancer vaccines, and natural killer cells. Additional examples of targeted therapies, novel “druggable” and other immunotargets are presented in the section, ”Future Directions.”
Reference
1. Couzin-Frankel, J., Breakthrough of the year 2013. Cancer immunotherapy. Science, 2013. 342(6165): p. 1432-3.
Human Stem Cells- Introduction
Types of HSC transplants
Indications
Sources of stem cells
Collection and mobilization
Types of Mobilizing agents
Processing
Cryopreservation and storage
PBSC Transplant
Quality control
Complications
Hematopoietic Stem Cells Transplantation for Multiple MyelomaWan Ning
Hematopoietic stem cells transplantation is a FDA-approved stem cells based therapy whereby it is usually performed for cancer patients. For an example, Multiple Myeloma.
Hematopoietic Stem Cell Harvesting and Mobilization.pptxroysudip900
procedure of bone marrow stem cell harvesting for bone marrow transplant by apheresis. mobilization of stem cell from bone marrow to peripheral blood. GCSF mobilization. Apheresis principle and procedure. stem cell from bone marrow collection. effect of stem cell collection form different sources. newer drugs for stem cell harvesting. adequate dose of stem cell to be collected. minimal invasive procedure.
Immunosupuression in adult liver transplantation Abhishek Yadav
Basics about immunosuppressive drugs in liver transplantation and protocols for immunosuppression in adult liver transplantation. Discusses the basic immunology of transplant, common drugs and protocols used in special scenarios in transplantation.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
2. What is a stem cell ?
• Stem cells are undifferentiated pluripotent precursors that are able to transform
into mature cells with specialized function.
• Stem cell pool is only 100,000 and if stem cell is damaged, a person can survive
only 2 to 4 weeks in absence of extraordinary support measures.
• Stem cells can undergo Self renewal and differentiation.
• In bone marrow hematopoietic stem cells are present in two niche areas.
1. Endosteal niche
2. Perivascular niche
These niche areas act as both a nutritive and constraining home for hematopoietic
stem cells.
3. • Hematopoietic stem cells anchor to these niche by means of receptors ( CXCR
4, VCAM 1) present on stem cells that interact with ligands ( CXCL12, VLA 4)
present on mesenchymal cells of bone marrow.
• G-CSF and Plerixafor target these interactions to mobilize stem cells from bone
marrow to peripheral blood.
5. • Hematopoietic cell transplantation is used to treat patients with both abnormal
but nonmalignant lymphohematopoietic system by replacing it with one from a
normal donor and malignancy by allowing the administration of higher doses of
myelosuppressive therapy than would otherwise be possible.
• The Center for International Blood and Marrow Transplant Research estimates
that worldwide about 100,000 transplants were performed in 2020.
• Transplantation of a small percentage of a donor’s bone marrow volume
regularly results in complete and sustained replacement of the recipient’s entire
lymphohematopoietic system, including all red cells, granulocytes, B and T
lymphocytes, and platelets, as well as the fixed macrophage population, like
Kupffer cells of the liver, pulmonary alveolar macrophages etc.
6. How the Hematopoietic stem cell transplantation has been made
clinically feasible ?
Hematopoietic stem cells has some special features:
1. Remarkable regenerative property.
2. Ability to home to marrow space following IV injection :
a) CXCL12- CXCR4 interaction
b) Selectin ( E & L- Selectin) Integrin ( VLA-4 ) interaction.
3. Ability to be cryopreserved.
7. Categories of Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation can be described by 2 means
1. According to relationship between patient and donor.
a) Syngeneic transplantation
b) Autologous transplantation
c) Allogenic transplantation
2. According to anatomic source of stem cell.
8. Syngeneic transplantation :
• Between identical twins.
• No risk of GVHD yet no risk of stem cells contaminated with tumour cells.
• GVT effect is absent hence post transplant relapse rate is higher.
Autologous transplantation :
• It involves removal, storage of patient’s own stem cells and post
myeloablative therapy reinfusion of those stem cells.
• No risk of GVHD or graft rejection.
• No GVT effect & high risk of stem cells being contaminated with tumour
cells. So,high relapse rate.
9. Allogenic transplantation :
• Donor and recipient are not genetically identical.
• High risk of GVHD and Graft rejection.
• GVT effect is seen.
10. Human leukocyte antigen (HLA) matching and Allogenic transplant
• HLA molecules are encoded by MHC complex genes.
• If donor and recipient are not HLA matched, T cells of one individual
strongly reacts to mismatched HLA of the second.
• HLA genes of major relevance are HLA- A, -B, -C, -D.
• Incidence of graft rejection and GVHD increases with no. of mismatched
HLA antigen.
• Survival following HLA matched unrelated donor transplant and HLA
matched sibling transplant are essentially the same due to improvement
in HLA typing and supportive care.
11. Categories of Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation can be described by 2 means
1. According to relationship between patient and donor.
a) Syngeneic transplantation
b) Autologous transplantation
c) Allogenic transplantation
2. According to anatomic source of stem cell.
a) Bone marrow graft
b) Peripheral blood stem cell graft
c) Cord blood graft
12. Bone marrow graft :
• Aspirated from posterior and anterior iliac crest.
• 10 -15 ml/kg volume of bone marrow is collected.
Cord blood graft :
• Umbilical cord contains high concentration of HSC.
• Peripheral count recovery takes longer time than that of BM transplant.
• Advantages: 1. Rapid availability of unrelated cord blood.
• 2. Decreased immune reactivity due to lower no of T cells in cord blood.
• The risk of graft failure and transplant related mortality are related to dose of cord
blood cells.
• Use of double cord transplant diminishes the risk of graft failure and early mortality.
13. Peripheral blood stem cell graft :
Hematopoietic stem cells circulate in the peripheral blood in very low
concentrations. Hence following steps are required.
• Donors are treated with granulocyte colony stimulating factor (G-CSF) for 4 to
5 days prior to collection day
• Stem cells are collected in one or two 4 hour leukapheresis sessions.
• Adequate number of stem cells (as measured by CD34) harvested.
Patients who fail to mobilize enough stem cells from marrow to peripheral blood
with G- CSF alone, the addition of Plerixafor (CXCR4 antagonist) may be useful.
14. Peripheral blood stem cell transplant versus bone marrow
transplant in allogenic transplantation
• Engraftment is faster in PBSC transplantation.
• Chronic GVHD is more in PBSC transplantation due to T cell contamination.
So, in case of unrelated matched donor, BM transplantation is favourable.
15. THE TRANSPLANT PREPARATIVE REGIMEN
• Reason: 1. To eradicate the patient’s underlying disease.
2. To immunosuppress the patient adequately to prevent graft
rejection in case of allogenic transplantation.
• The appropriate regimen therefore depends on the disease setting and graft
source.
For example,
1. In severe combined immunodeficiency (SCID) if the donor is a
histocompatible sibling, no treatment is needed because no host cells require
eradication and the patient is already too immune-incompetent to reject the
transplanted graft.
16. 2. For aplastic anemia, there is no large population of cells to eradicate, only
immunosuppression is adequate.
Regimen used: High dose cyclophosphamide plus Antithymocyte globulin.
3. In thalassemia and Sickle cell anemia, there is hyperplastic host
hematopoiesis.
Regimen used: Cyclophosphamide plus high dose Busulfan (for myelosuppression)
4. In malignant diseases: Various regimen are used. Most of them use high
activity against tumor in question at conventional doses with myelosuppression
as their dose limiting toxicity.
Drugs used : Busulfan, cyclophosphamide, melphalan, etoposide, total body
irradiation in various combinations
17. Newer concept of Preparative conditioning
Although high dose treatment regimen were used initially, realization of graft versus
tumor (GVT) effect warrened use of following alternative regimens.
1. Nonmyeloablative regimen: Only transient myelosuppression is seen if no
transplantation is performed.
Fludarabine plus total body irradiation used.
2. Reduced intensity regimen: It causes significant but not necessarily fatal
myelosuppression in the absence of transplantation
Fludarabine plus melphalan used.
But relapse rates are higher in these regimens hence they are used if patient can
not tolerate the Myeloablative conditioning or has significant comorbidities.
18. ENGRAFTMENT AND IMMUNE RECONSTITUTION
What is Engraftment?
• Neutrophils engraftment and platelet engraftment
• ANC > 500 for at least 3 days,1st day of these 3 days is called 'Day of
neutrophil engraftment’
• Platelet count >20000 for at least 7 days without transfusion support, 1st day of
these 7 days is called 'Day of platelet engraftment'.
19. • Rate of engraftment depends upon source of stem cell.
PBSC graft-2 weeks
BM graft- 3 weeks
Cord blood graft- 4 weeks
• Use of post transplant myeloid growth factor accelerates recovery by 3-5 days.
20. • Components of innate immunity ( granulocytes and macrophages) recover rapidly
following transplant.
• Adaptive immunity takes longer time to recover.
T cells- for initial months CD8+ T cells with limited receptoire are there. Later,
donor derived CD4+ and CD8+ T cells becomes dominant with diverse T-cell
repertoire.
B cells- Recovers 6 months after autologous HSCT and 9 months after allogeneic
HSCT.
• In general, immunity recovery occurs more rapidly after autologous HSCT.
• Method of documentation of engraftment:
1. Short tandem repeat polymorphism
2. fluorescence in situ hybridization (FISH) of sex chromosomes. ( In sex
mismatched transplant)
22. • Early direct chemo radiotoxicity
Nausea, vomiting, mild skin erythema
Hair loss
Profound pancytopenia
Hemorrhagic cystitis - Due to use of high dose cyclophosphamide.
Treatment- bladder irrigation, MESNA
Oral mucositis- typically develops 5–7 days after transplant.
Treatment- narcotic analgesia, Palifermin (keratinocyte growth factor) can
shorten duration.
23. Sinusoidal obstruction syndrome (SOS) of liver
Due to direct cytotoxic injury to hepatic-venular and sinusoidal
endothelium, with subsequent deposition of fibrin and the development of a
hypercoagulable state.
- Peak incidence at day 16 post transplant.
- Mortality-30%
- C/F- Tender hepatomegaly, ascites, jaundice
- Treatment- Defibrotide ( a polydeoxyribonucleotide)
Diffuse interstitial pneumonia- Treatment- High-dose glucocorticoids.
24. Transplant associated thrombotic microangiopathy
- Characterized by presence of schistocytes on peripheral smear, elevated
lactate dehydrogenase, thrombocytopenia, and acute kidney injury.
- Calcineurin inhibitors are thought to contribute to the pathogenesis.
- Treatment- Changing immunosuppressive regimens
Eculizumab may be used.
25. • Late Direct Chemoradiotoxicities
Pulmonary complications
Two categories of chronic pulmonary disease.
A. Cryptologic organizing pneumonia
- A restrictive lung disease, presents with dry cough and SOB.
- Treatment- responds well to corticosteroids. (entirely reversible)
B. Bronchiolitis obliterans-
- An obstructive lung disease, presents with cough and progressive
dyspnea.
- Usually associated with chronic GVHD.
- Treatment- Responds somewhat to increasing immunosupression but
complete reversal is uncommon.
26. Decreased growth velocity in children and delayed development of secondary sex
characteristics- Most men become azoospermic, and most postpubertal women
develop ovarian failure.
Cataracts and Aseptic necrosis of the femoral head- both are due to chronic
glucocorticoid therapy.
27. Graft failure
Characterized by non return of marrow function following transplant or it's
loss after a brief period of engraftment.
• Following autologous transplantation, can be due to
- Inadequate stem cell transplantation
- Damage during storage
- Exposure of the patient to myelotoxic agents after transplant
- Infections with cytomegalovirus (CMV) or human herpesvirus type 6.
• Following allogenic transplantation, can be due to
- Graft rejection by immunocompetent cells of recipient
- Poor engraftment due to presence of pretransplant donor-specific HLA
antibodies in the patient.
• Treatment- Removal of all myelotoxic agents and short trial of a myeloid growth
factor.
28. Graft Versus Host Disease
It is caused by immune cells transplanted with the stem cells or developing
from them that react against the patient following allogeneic transplantation.
Types : a. Acute GVHD
b. Chronic GVHD
c. Late onset acute GVHD
29. Acute GVHD
- Occurs within 3 months.
- Risk factors- Mismatched or unrelated donors, Older patients, Multiparous
female donors etc.
- Clinical features: maculopapular rash, persistent anorexia or diarrhea, or
both, liver disease with increased liver enzymes.
- Grades- I to IV. Grade I shows mild symptoms and no change in survival.
But grade II to IV associated with serious symptoms and poor survival rate.
- Treatment – Prednisone. If response is inadequate, oral JAK2 inhibitor
ruxolitinib can be tried.
- Prophylaxis- CNI + MTX/ MMF +/- ATG
30. Chronic GVHD
- Occurs 3 months to 2 years post transplant.
- Risk factors- older patients, use of peripheral blood stem cells, recipients
of mismatched or unrelated stem cells, previous episode of acute GVHD.
- Clinical features: It resembles an autoimmune disorder with malar rash,
sicca syndrome, arthritis etc.
- Treatment: Mild chronic GVHD- local therapies.
Severe disease- Systemic therapy with prednisone alone or in
combination with Cyclosporine.
Late onset acute GVHD
- It is acute GVHD after 3 months.
- It shows clinical features of both acute and chronic GVHD also called
overlap syndrome.
31.
32. Infections
Posttransplant patients, particularly recipients of allogeneic transplantation
are at great risk of developing infections due to various microbes.