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Chapter 20: Leukemia, Chronic Myelogenous

Michael W.N. Deininger; Brian J. Druker

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    AMA Citation
    Deininger MN, Druker BJ. Deininger M.N., Druker B.J. Deininger, Michael W.N., and Brian J. Druker.Leukemia, Chronic Myelogenous. In: Boyiadzis MM, Frame JN, Kohler DR, Fojo T. Boyiadzis M.M., Frame J.N., Kohler D.R., Fojo T Eds. Michael M. Boyiadzis, et al.eds. Hematology-Oncology Therapy, 2e New York, NY: McGraw-Hill; . http://hemonc.mhmedical.com/content.aspx?bookid=1611&sectionid=126323171. Accessed February 18, 2019.
    MLA Citation
    Deininger MN, Druker BJ. Deininger M.N., Druker B.J. Deininger, Michael W.N., and Brian J. Druker.. "Leukemia, Chronic Myelogenous." Hematology-Oncology Therapy, 2e Boyiadzis MM, Frame JN, Kohler DR, Fojo T. Boyiadzis M.M., Frame J.N., Kohler D.R., Fojo T Eds. Michael M. Boyiadzis, et al. New York, NY: McGraw-Hill, , http://hemonc.mhmedical.com/content.aspx?bookid=1611&sectionid=126323171.

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INTRODUCTION

Epidemiology

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Epidemiology
Incidence: 5,980 (male: 3,130; female: 2,850. Phase at presentation:
Estimated new cases for 2014 in the United States) Chronic phase: 85–90%
Deaths: Estimated 810 in 2014 (male: 550; female: 260) Accelerated phase and blast crisis: 10–15%
Median age: 65 years  
Male to female ratio: 1.7:1  

Cervantes F et al. Haematologica 1999;84:324–327

O'Brien SG et al. N Engl J Med 2003;348:994–1004

Siegel R et al. CA Cancer J Clin 2014;64:9–29

Surveillance, Epidemiology and End Results (SEER) Program, available from http://seer.cancer.gov (accessed in 2013)

Pathology

Peripheral blood findings at diagnosis: median (range)

  1. WBC: 174,000/mm3 (15–850/mm3)

  2. Hemoglobin: 10.3 g/dL (4.9–16.6 g/dL)

  3. Platelet count: 430,000/mm3 (17–3182/mm3)

  4. Left-shifted white cell differential, basophilia, and eosinophilia

  5. Blasts: <15%—chronic phase

Bone marrow findings at diagnosis

  1. Increased cellularity

  2. Increased myeloid-to-erythroid ratio with full myeloid maturation

  3. Blasts <15%—chronic phase

  4. Basophilia

  5. Megakaryocyte hyperplasia

  6. Reticulin fibrosis

Cytogenetics and molecular diagnostics

  1. Philadelphia (Ph) chromosome including variant translocations (90%)

  2. BCR-ABL translocation by FISH (95%)✫

  3. BCR-ABL transcripts by RT-PCR (95%)✫

  4. Chromosomal abnormalities in addition to the Ph chromosome (clonal evolution)†:

    (Associated with disease progression, usually absent in the chronic phase at diagnosis)

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Pathology
Trisomy 8 52.9%
Second Philadelphia chromosome 50.7%
Isochromosome 17 35.8%
Trisomy 19 24.3%

 

Deininger MWN. Semin Hematol 2003;40(2 Suppl 2):50–55

Johansson B et al. Acta Haematol 2002;107:76–94

Mitelman F. Leuk Lymphoma 1993;11(Suppl 1):11–15

Savage DG et al. Br J Haematol 1997;96:111–116

Thiele J et al. Leuk Lymphoma 2000;36:295–308

Work-up

History and physical examination

  1. CBC and leukocyte differential counts, platelets, electrolytes, liver function tests

  2. HLA typing for patients who are candidates for allogeneic hematopoietic cell transplantation

  3. Bone marrow aspirate and biopsy (bone marrow cytogenetics can detect chromosomal abnormalities other than Ph chromosome that are not detectable using peripheral blood)

  4. BCR-ABL1 transcript levels by quantitative reverse transcriptase polymerase reaction (QPCR) before initiation of treatment.

  5. If collection of bone marrow is not feasible, fluorescence in situ hybridization (FISH) on a peripheral blood specimen with dual probes for BCR and ABL1 genes

Classification of Disease: Phases of Disease

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Classification of Disease: Phases of Disease
Chronic phase:

  1. Bone marrow and peripheral blood blasts <15%

  2. Peripheral blood promyelocytes and blasts combined <30%

  3. Peripheral blood basophils <20%

  4. Platelets >100,000/mm3
Accelerated phase:

  1. Bone marrow and peripheral blood blasts 15–30%

  2. Peripheral blood promyelocytes + blasts ≥30% (but blasts alone <30%)

  3. Peripheral blood basophils ≥20%

  4. Platelets ≤100,000/mm3 (unless related to therapy)
Blast crisis:

  1. Bone marrow or peripheral blood blasts ≥30%

  2. Myeloid immunophenotype: MPO-positive

  3. Lymphoid immunophenotype: TdT-positive

Cytogenetic abnormalities in addition to the Philadelphia chromosome (typically, isochromosome 17, trisomy 8, trisomy 19, second Ph chromosome) are considered indicative of accelerated phase by some authors, even in the absence of other defining criteria. Adverse prognostic significance is best documented for isochromosome 17

Johansson B et ...

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