The document discusses the classification and treatment of various types of leukemia. It begins by defining leukemia as the neoplastic proliferation of white blood cells. Leukemias are classified as either lymphoid or myeloid and as either acute or chronic depending on the affected cell type and disease progression. The four major types are described as acute lymphocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia and chronic myelogenous leukemia. Treatment options are discussed including chemotherapy regimens, bone marrow transplantation, supportive care and goals of treatment.
Learning Objectives:
Introduction
Definition of CML
Philadelphia Chromosome
Normal Granulopoiesis
Pathogenesis of CML
Aetiology
Incidence
Clinical Features
Phases of CML
Lab Diagnosis of CML
Course & Prognosis
Differential Diagnosis
Brief Overview of Treatment
Learning Objectives:
Introduction
Definition of CML
Philadelphia Chromosome
Normal Granulopoiesis
Pathogenesis of CML
Aetiology
Incidence
Clinical Features
Phases of CML
Lab Diagnosis of CML
Course & Prognosis
Differential Diagnosis
Brief Overview of Treatment
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
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An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
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The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Model Attribute Check Company Auto PropertyCeline George
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Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
1. The Leukemias
By
Dr CK Mwandama
Department of Internal medicine,
University Teaching Hospital, Lusaka
29/06/17
2. Introduction
Definition
• The word leukemia literally means “white blood” referring to
neoplastic proliferation of white blood cells or leukocytes.
• Leukemias are haematologic neoplasms characterized by clonal
malignant proliferation of either mature white blood cells or their
precursors.
5. Classification of Leukemia
• Leukemias are classified as lymphoid or myeloid, depending on the
affected progenitor stem cell type.
• Leukemias are also classified as acute or chronic depending on the
duration of evolution of the disease
6. Classification of leukemia
Leukaemias are classified in 4 major types
Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
8. Classification of leukemias
Acute Leukaemias
• In acute leukemias onset of disease is often abrupt, within weeks,
and death may occur within weeks to months without treatment.
• Typically, leukocyte development halts at the blast phase with most
leukocytes undifferentiated or blasts.
• In acute leukemia, the WBC may remain low because the cells are
halted at the blast stage
9. Classification of Leukemias
Chronic Leukaemias
• Onset is much slower, often over months or years.
• The majority of leukocytes are mature
• Typically manifest with very high WBC counts
10. Pathophysiology of Leukemia
Leukemias appears to result from a combination of factors
• genetic predisposition
• chromosomal changes
• chemical agents(benzene)
• chemotherapeutic agents.
• radiation
• immunocompromise
• viruses
12. Pathophysiology of Leukemias
Leukemogenesis is characterized by ;
• blockage of cell differentiation
• self-sustainable proliferation
• abnormal cell cycle progression
• impaired apoptosis
13. Pathophysiology of Leukemia
Genetic abnormalities identified in the propagation of leukemogenesis
include
chromosomal translocations
gene deletions
Amplifications
point mutations
14. Pathophysiology of Leukemia
Proto-oncogenes associated with leukemogenesis include
ABL-Chronic myeloid leukemia
N- Ras-Haematologic Malignancies
FMS-Leukemia
c-MYC- Burkitts Leukemia
15. Acute Lymphoblastic Leukemia
Characterized by presence of lymphoblasts in the bone marrow,
peripheral blood ,liver, spleen, lymph nodes and soft tissues
Philadelphia chromosome positive(t9:22 translocation)
Classified into 3 stages
• L1: Small homogeneous blasts; mostly in children
• L2: Large heterogeneous blasts; mostly in adults
• L3: “Burkitt” large basophilic B-cell blasts with vacuoles
16. Acute Myeloid Leukemia
Characterized by uncontrolled proliferation of myeloblasts, hyperplasia
of bone marrow and spleen
FAB Classification
• M0 -- Undifferentiated AML
• M1 -- AML without maturation
• M2 -- AML with maturation
• M3 -- Acute Promyelocytic Leukemia
• M4 -- Acute Myelomonocytic Leukemia
• M5 -- Acute Monocytic Leukemia
• M6 -- Erythroleukemia (DiGuglielmo’s)
• M7 -- Megakaryoblastic Leukemia
17. Acute Myeloid Leukemia
WHO classification
• AML with recurrent cytogenic translocations
• AML with multi-lineage dysplasia
• AML and myelodysplasia, therapy related
• AML, not otherwise categorized
19. Chronic myeloid Leukemia
• Characterized by excessive development of mature neoplastic
granulocytes in the bone marrow and peripheral blood
• Ultimately infiltration into the liver and spleen
• Philadelphia chromosome(Ph) is present in up to 95% of patients
• Characterized by reciprocal translocation of long arm of
chromosomes 22 and chromosome 9
• Ph chromosome is almost specific to CML
20. Chronic myeloid Leukemia
• Abelson proto-oncogene (c-ABL) come into juxtaposition with the
“break point cluster region”(BCR) producing the BCR-ABL fusion
oncogene
• Resultant oncoprotein is a hyperactive tyrosine kinase
• Ph chromosome is also seen in ALL and chronic neutrophilic
leukemia
21. Chronic Lymphocytic Leukemia
• Exclusive in elderly
• Hyper-mature lymphocytes with highly condensed nuclei
• Massive splenomegaly and Lymph node enlargement is noticeable
throughout the body
22. Chronic Lymphocytic Leukemia
CLL is staged as follows
Stage 0-Absolute lymphocyte count >15 000
Stage 1-Absolute lymphocytosis with lymphadenopathy
Stage 2-Absolute lymphocytosis with lymphadenopathy with
hepatomegaly and or splenomegaly
Stage 3-Absolute lymphocytosis with lymphadenopathy with
hepatomegaly and or splenomegaly plus anaemia(Hb <11)
Stage 4-Absolute lymphocytosis with lymphadenopathy with
hepatomegaly and or splenomegaly plus
thrombocytopenia(platelet count < 100 000)
23. Overall clinical features
Bone Marrow Failure
Anemia
Neutropenia
Thrombocytopenia
Infiltration
Leukemia meningitis Hepatosplenomegaly
Central nerve palsy Granulocytic sarcoma
Leukemic orchitis Lymphadenopathy
Hyperleukocytosis
Central nervous system leukostasis/stroke
Respiratory distress syndrome
Metabolic
Hypercalcemia Hyperphosphatemia
Hyperkalemia Hypercoagulation
Hyperuricemia Weight loss
24. Overall Clinical features
ALL AML CLL CML
Signs/Symptoms Fatigue, weight loss, night
sweats, bruising, bleeding
Fatigue, weight loss, night
sweats
White blood cell High/low High/low High High
Hemoglobin Normal/low Normal/low Normal/low Normal
Platelets Low Low Normal/high Normal/high
BM Blasts > 20% > 20% None 0-10%
Chronic Phase
Spleen/Liver May be
enlarged
Normal May be
enlarged
May be
enlarged
25. Approach to Diagnosis
• Medical history and physical
• CBC with differential
• Bone marrow biopsy and aspiration
• Chemistry panel
• Cytogenetics
• Immunophenotyping
27. Chemotherapy for Acute Leukemias
ALL AML
Class Agents Class Agents
Vinca Alkaloids Vincristine Anthracyclines Daunorubicin
Idarubicin
Corticosteroids Dexamethasone
Prednisone
Pyrimidine Analog Cytarabine
Anthracyclines Doxorubicin
Daunorubicin
Antimetabolite Hydroxyurea
Antimetabolite Methotrexate
Alkylator Cyclophosphamide
Enzyme L- Asparaginase
28. Chemotherapy for Chronic Leukemia
CLL CML
Class Agents Class Agents
Purine analog Fludarabine Tyrosine kinase
inhibitors
Imatinib, Dasatinib
Nilotinib
Steroids Methylprednisolone
Alkylators Cyclophosphamide,
Chlorambucil,
Bendamustine
Monoclonal
antibodies
Rituximab,
Alemtuzumab,
Ofatumumab
29. Bone Marrow /Stem cell transplant
Goals of this therapy are as follows
• Total myelosuppression of patient’s neoplastic BM
• Transplant an HLA-matched BM from any of the following
• Patient’s own stem cells removed before
• Identical twin
• Sibling
• Volunteer
30. Supportive care
• Isolation with total barrier nursing
• Blood and platelets transfusion
• Antibiotic cover
• G-CSF
• Anti-emetics
• Prevention of tumor lysis syndrome
31. References
• Oxford Handbook of Clinical Haematology,
2nd Edition
• Oxford Handbook of Clinical Medicine, 9th
Edition