Chronic Myeloid Leukemia Overview

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.