Chronic Myelogenous Leukemia

Aka: Chronic Myelogenous Leukemia, Chronic Myeloid Leukemia, CML, Philadelphia Chromosome, BCR-ABL1 Fusion Gene

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II. Epidemiology

  1. Common in Atomic bomb survivors
  2. Peak Incidence at ages 30 to 50 years old

III. Pathophysiology

  1. Chronic phase (Mild, indolent course)
    1. Excessive Granulocyte (Neutrophils) proliferation
  2. Blastic phase (Malignant, leukemic course)
    1. Increased blasts and Promyelocytes

IV. Symptoms

  1. Asymptomatic in 20% of patients
  2. Weakness
  3. Hypermetabolism
    1. Weight loss
    2. Fever
  4. Arthralgias
  5. Bone pain
  6. Excessive bleeding (spontaneous or with surgery)

V. Signs

  1. Splenomegaly (90%)
  2. Hepatomegaly
  3. Lymphadenopathy

VI. Labs

  1. Philadelphia Chromosome (BCR-ABL1 Fusion Gene)
    1. Present in 90 to 95% of CML cases on peripheral blood or Bone Marrow testing
      1. Also present in ALL (2-4% of children, 20-40% of adults)
    2. Reciprocal Chromosome translocation
      1. Long arm of Chromosome 22 (c-sis Oncogene)
      2. Long arm of Chromosome 9 (c-abl Oncogene)
    3. Translocation of C-abl at bcr breakpoint
      1. Forms bcr/abl
  2. Complete Blood Count
    1. Chronic Phase
      1. White Blood Cell Count > 200,000/uL
      2. Granulocytes (especially Neutrophils) predominate
    2. Transitional Phase (50% of patients)
      1. Leukocytosis
      2. Thrombocytosis or Thrombocytopenia
    3. Blast Phase
      1. Increased Leukocytosis
      2. Thrombocytosis
  3. Bone Marrow Biopsy and Peripheral Smear
    1. Chronic Phase
      1. Myeloblasts represent <5% of cells
    2. Blast Phase
      1. Large proportion of immature cells
    3. Images
      1. HemeoncCmlBlood.jpg
      2. HemeoncCmlMarrow.jpg
      3. HemeoncCmlBlastCrisis.jpg
  4. Other Findings
    1. Vitamin B12 markedly elevated
    2. Leukocyte Alkaline Phosphatase reduced
    3. Uric Acid increased

VII. Management: CML Treatment

  1. Treatment for cure
    1. Allogeneic Stem Cell Transplant (SCT)
  2. Chronic Phase suppression
    1. First Line
      1. Tyrosine Kinase Inhibitor: Imatinib (Gleevac)
        1. Gleevac is generic in U.S. as of February 2016
        2. Monitor for complications (thrombotic events, CV and GI complications)
        3. Monitor CBC every 3 months
      2. Interferon-alfa with Cytarabine
        1. May be poorly tolerated
        2. Studies to date show unclear efficacy
          1. Baccarani (2002) Blood 99:1527 [PubMed]
          2. Guilhot (1997) N Engl J Med 337:223 [PubMed]
    2. Alternative (prior first line agents)
      1. Hydroxyurea (used to stabilize chronic phase)
      2. Busulfan
        1. Risk of myelosuppression
        2. Hydroxyurea is preferred
    3. Other Alkylating Agents (not in marrow transplant)
      1. Cytarabine
      2. Cyclophosphamide
      3. Melphalan
    4. Splenectomy rarely indicated
      1. Hypersplenism
      2. Repeated painful splenic infarctions
    5. Consider Bone Marrow Transplantation in first year
      1. Results in 70% long-term disease free survival
  3. Blast Crisis
    1. Often refractory to treatment
      1. Hydroxyurea
    2. Try protocols for Acute Lymphocytic Leukemia
      1. Vincristine
      2. Prednisone

VIII. Management: Surveillance of CML Survivors

  1. Complete Blood Count (CBC) every 3 months
    1. Hematology Consultation for Neutropenia (ANC <1000/mm3) or Thrombocytopenia (Platelet Count <50k/mm3)
  2. Symptom surveillance
    1. Diarrhea
    2. Fluid retention
    3. Nausea or Vomiting
    4. Headache
    5. Myalgias
    6. Rash
  3. Patients treated with Hematopoietic Stem Cell Transplantation
    1. See Hematopoietic Stem Cell Transplant for protocol

IX. Course

  1. Initially indolent
  2. Later progresses to leukemic phase (Blast Crisis)
    1. Blast phase onset after 6-12 months post diagnosis
    2. Annual progression to blast phase: 25% of patients

X. Prognosis

  1. Five year survival
    1. Age under 50 years old: 84% five year survival
    2. Age over 50 years old: 48% five year survival

XI. References

  1. (2001) Med Lett Drugs Ther 43(1106):49-50
  2. Druker in Abeloff (2004) Clinical Oncology p. 2899-915
  3. Enright in Hoffman (2000) Hematology 40:1155-67
  4. Davis (2014) Am Fam Physician 89(9): 731-8 [PubMed]
  5. Gbenjo (2023) Am Fam Physician 107(4): 397-405 [PubMed]

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