Chronic Myeloid Leukemia Overview

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Questions and Answers

What is the role of monitoring BCR-ABL transcripts in the treatment of Chronic Myeloid Leukemia (CML)?

Monitoring BCR-ABL transcripts is crucial for assessing the response to treatment and disease progression in CML.

Describe the pathophysiology of Polycythemia Vera (PV).

Polycythemia Vera is a chronic myeloproliferative disorder characterized by an excessive production of red blood cells due to a clonal proliferation in the bone marrow.

What diagnostic methods are commonly used to confirm Chronic Myeloid Leukemia (CML)?

Diagnosis of CML typically involves blood tests, a bone marrow biopsy, and immunophenotyping through flow cytometry.

What are the procedures involved in a bone marrow biopsy?

A bone marrow biopsy involves obtaining a small sample of bone marrow, usually from the posterior iliac crest, using a hollow needle. Signup and view all the answers

How do erythropoietin levels influence secondary polycythemia?

Erythropoietin levels can trigger secondary polycythemia by causing increased red blood cell production in response to hypoxia or pathologic conditions. Signup and view all the answers

What is the mainstay treatment for Polycythemia Vera (PV) and its target hematocrit levels for men and women?

The mainstay treatment for PV is phlebotomy, with target hematocrit levels below 45% for men and below 42% for women. Signup and view all the answers

Discuss the pathophysiology of Polycythemia Vera and the role of the JAK2V617F mutation.

Polycythemia Vera results from uncontrolled cell proliferation, leading to an overproduction of red and white blood cells, attributed mainly to the JAK2V617F somatic mutation. Signup and view all the answers

What diagnostic criteria should be met to establish a diagnosis of Polycythemia Vera?

A diagnosis of Polycythemia Vera is established with raised red cell mass, normal O2 saturation, and absence of BCR-ABL fusion, alongside either another 'A' or two 'B' criteria. Signup and view all the answers

Explain the procedure and significance of a bone marrow biopsy in diagnosing Myeloproliferative Disorders.

A bone marrow biopsy involves sampling the bone marrow to assess for megakaryocytic hyperplasia and is significant for diagnosing conditions like Essential Thrombocythemia. Signup and view all the answers

How does Erythropoietin (EPO) relate to the pathology of Polycythemia Vera?

In Polycythemia Vera, EPO levels are typically normal or suppressed, as the disease is characterized by increased red blood cell mass independent of EPO stimulation. Signup and view all the answers

Study Notes

Monitoring BCR-ABL Transcripts

Essential for evaluating treatment response and disease progression in CML.

Immunophenotyping Techniques

Flow cytometry and immunohistochemistry are used to identify cell surface markers in bone marrow to characterize abnormal populations.

Treatment Timeline of Chronic Myeloid Leukemia (CML)

Various therapies developed over the years include:
- Arsenic (Lissauer, 1865)
- Radiotherapy (Pusey, 1902)
- Busulfan (Galton, 1953)
- Hydroxyurea (Fishbein et al, 1964)
- Autografting (Buckner et al, 1974)
- Allogeneic Bone Marrow Transplant (BMT) (Doney et al, 1978)
- Interferon (Talpaz et al, 1983)
- Donor Leukocytes (Kolb et al, 1990)
- Imatinib (Druker et al, 1998)
- Combination therapies with Imatinib (O'Brien et al, ongoing)

Allogeneic Bone Marrow Transplant Issues

Offers a 70% long-term cure rate.
Factors affecting success include:
- Donor availability
- Patient age
- Duration/stage of disease
- Treatment-related mortality
- Long-term complications like infertility and chronic graft-versus-host disease (cGVHD).

CML Diagnosis and Treatment Strategy

Young patients with a suitable donor start Imatinib at 400 mg/day.
Poor responders may consider allograft; good response leads to indefinite Imatinib use.

Polycythemia Vera (PV) Overview

Chronic myeloproliferative neoplasm causing excessive red blood cell production, leading to increased blood viscosity and potential cardiovascular complications.

Types of Polycythemia

True/Absolute: Includes primary and secondary causes.
Apparent/Relative: Results from decreased plasma volume.

Causes of Secondary Polycythemia

Erythropoietin (EPO)-mediated:
- Hypoxia-driven factors: chronic lung diseases, high-altitude exposure, and certain heart conditions.
- Hypoxia-independent: caused by tumors and renal conditions.
EPO receptor-mediated mutations and drug associations like EPO doping contribute to red blood cell production.

JAK2 Mutation in PV

Key genetic abnormality leading to uncontrolled cell growth and overproduction of blood cells.
JAK2V617F mutation found in most PV patients.

Clinical Features of PV

Symptoms include elevated hemoglobin levels, leukocytosis, thrombocytosis, splenomegaly, and pruritus.
Associated with rare thrombosis events and erythromelalgia.

Complications of PV

High blood pressure, gout, transformation to leukemia, and myelofibrosis.

PV Diagnostic Criteria

Requires evidence of elevated red cell mass, normal oxygen saturation and EPO levels, a palpable spleen, and absence of BCR-ABL fusion.
Accompanied by thrombocytosis, neutrophilia, radiological findings of splenomegaly, or endogenous erythroid colonies.

PV Treatment Options

Mainstay: phlebotomy to maintain hematocrit < 45% in men, < 42% in women.
Hydroxyurea and aspirin are used for high-risk thrombosis patients.
Additional treatments include interferon for pruritus, anagrelide for thrombocytosis, and allopurinol for gout.

Essential Thrombocythemia (ET)

Persistent platelet count > 600 x10^9/L.
Characterized by megakaryocytic hyperplasia without the Philadelphia chromosome.
Affects 2.5 per 100,000 with median diagnosis at 60 years.

Myeloproliferative Disorders Classification

Includes CML, PV, ET, and myelofibrosis, with distinct clinicopathologic features yet common underpinnings.

Epidemiology of CML

Accounts for 15-20% of adult leukemias.
Median diagnosis age ranges from 50 to 60 years, but can occur at any age.
Characterized by BCR-ABL fusion from translocation between chromosomes 9 and 22.

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Description

This quiz covers essential aspects of Chronic Myeloid Leukemia (CML), including the significance of monitoring BCR-ABL transcripts and techniques such as flow cytometry and immunohistochemistry. Additionally, it explores diagnostic tools like blood pictures and bone marrow biopsies, as well as various treatment options for CML.