Hematology and Oncology Book

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Bone Marrow Disorders

Lymphatic Disorders

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Chronic Myelogenous LeukemiaAka: CML

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  1. Epidemiology
    1. Common in Atomic bomb survivors
    2. Peak Incidence at ages 30 to 50 years old
  2. Pathophysiology
    1. Chronic phase (Mild, indolent course)
      1. Excessive Granulocyte (Neutrophils) proliferation
    2. Blastic phase (Malignant, leukemic course)
      1. Increased blasts and Promyelocytes
  3. Symptoms
    1. Weakness
    2. Hypermetabolism
      1. Weight loss
      2. Fever
    3. Arthralgias
    4. Bone pain
    5. Excessive bleeding (spontaneous or with surgery)
  4. Signs
    1. Splenomegaly (90%)
    2. Hepatomegaly
    3. Lymphadenopathy
  5. Labs
    1. Philadelphia chromosome (95%)
      1. Reciprocal chromosome translocation
        1. Long arm of chromosome 22 (c-sis oncogene)
        2. Long arm of chromosome 9 (c-abl oncogene)
      2. 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. Vitamin B12 markedly elevated
    5. Leukocyte Alkaline Phosphatase reduced
    6. Uric Acid increased
  6. Management
    1. Treatment for cure
      1. Allogeneic Stem Cell Transplant (SCT)
    2. Chronic Phase suppression
      1. First Line
        1. Tyrosine Kinase inhibitor: Imatinib (Gleevac)
        2. Interferon-alfa with Cytarabine or
          1. May be poorly tolerated
          2. Studies to date show unclear efficacy
            1. Baccarani (2002) Blood 99:1527
            2. Guilhot (1997) N Engl J Med 337:223
      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
  7. 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
    3. Life expectancy 3.5 years from diagnosis
  8. References
    1. (2001) Med Lett Drugs Ther 43(1106):49
    2. Druker in Abeloff (2004) Clinical Oncology p. 2899-915
    3. Enright in Hoffman (2000) Hematology 40:1155-67

Myeloid Leukemia, Chronic (C0023473)

Definition (CSP)chronic leukemia in which myeloid progenitor cells predominate; the hallmark of CML, the Philadelphia chromosome, is a reciprocal translocation between chromosomes 9 and 22 which activates the proto- oncogene c-abl.
Definition (NCI)A slowly progressing disease in which too many white blood cells are made in the bone marrow.
Definition (MSH)Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Definition (NCI)The most common chronic myeloproliferative disorder characterized by neutrophilic leukocytosis. It is associated with the Philadelphia (Ph) chromosome and/or the BCR/ABL fusion gene. Most patients are middle-aged or elderly. Common findings at presentation include fatigue, weight loss, anemia, night sweats, and splenomegaly. The disease is bi- or triphasic: an initial indolent chronic phase is followed by accelerated or blast phase. Allogeneic bone marrow transplantation is currently the only curative therapy (adapted from WHO 2001).
ConceptsNeoplastic Process (T191)
ICD9205.1
MSHD015464
EnglishCGL, CGL - Chronic granulocytic leukaemia, CGL - Chronic granulocytic leukemia, Chronic granulocytic leukaemia, Chronic Granulocytic Leukemia, Chronic Granulocytic Leukemias, Chronic myelocytic leukaemia, Chronic Myelocytic Leukemia, Chronic Myelocytic Leukemias, Chronic myelogenous leukaemia, Chronic Myelogenous Leukemia, Chronic Myelogenous Leukemias, Chronic myeloid leukaemia, Chronic Myeloid Leukemia, Chronic Myeloid Leukemias, CML, CML - Chronic Myelogenous Leukemia, CML - Chronic myeloid leukaemia, CML - Chronic myeloid leukemia, LEUKEMIA CHRONIC MYELOCYTIC, LEUKEMIA MYELOCYTIC CHRONIC, LEUKEMIA PHILA POS, Ph1-Positive Myelogenous Leukemia, Ph1-Positive Myelogenous Leukemias, Ph1-Positive Myeloid Leukemia, Ph1-Positive Myeloid Leukemias, Philadelphia-Positive Myeloid Leukemia, Philadelphia-Positive Myeloid Leukemias
Spanishleucemia granulocitica cronica, leucemia mielocitica cronica, leucemia mielogena cronica, leucemia mieloide cronica
Parent ConceptsMyeloid Leukemia (C0023470), Chronic leukemia (category) (C1279296), Malignant Neoplasms (C0006826), Leukocyte Abnormalities, General and NEC (C0549532), Myeloproliferative disease (C0027022), Chronic myeloproliferative disorder (C1292778), Common Hematopoietic Neoplasm (C1333131), Myeloid Leukemia, Chronic (C0023473), Chronic myeloid leukemia - category (C1531667), Duplicate concept (C1274013)
SourcesCOSTAR, CSP, CST, DXP, ICD9CM, MSH, MTH, NCI, NDFRT, OMIM, PDQ, QMR, SCTSPA, SNOMEDCT
Derived from the NIH UMLS (Unified Medical Language System)



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