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INTRODUCTION

Epidemiology

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Epidemiology
Incidence: Estimated new cases for 2019 in the United States: 8990 (male: 5250; female: 3740) Phase at Presentation
Deaths: Estimated 1140 in 2019 (male: 660; female: 480) Chronic phase: 85–90%
Median age: 65 years Accelerated phase and blast crisis: 10–15%

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 2019;69:7–34

Surveillance, Epidemiology and End Results (SEER) Program, available from http://seer.cancer.gov (accessed in 2019)

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)

    • Rare in chronic phase at diagnosis, common in accelerated and blast phase

    • Major route abnormalities: trisomy 8, trisomy 19, second Ph and isochromosome 17

    • Minor route abnormalities: all others except loss of Y chromosome

    • Major route abnormalities at diagnosis in chronic phase are associated with shorter progression-free and overall survival with imatinib

    • Some minor route abnormalities such as deletion 7 and 3q26.2 abnormalities also carry a poor prognosis

    • Newly acquired chromosomal abnormalities on therapy define progression to accelerated phase

Approximately 5% of patients with morphologically and clinically typical CML are negative for BCR-ABL by FISH and RT-PCR; these patients do not have CML but constitute a heterogeneous group including atypical CML, chronic neutrophilic leukemia, and non-classifiable myeloproliferative neoplasms. They do not respond to imatinib or other tyrosine kinase inhibitors. The data given here do not apply to this group of patients

 

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

Fabarius A et al. Blood 2011;118;6760–6768

Wang W et al. Blood 2016;127:2742–2750

Deininger et al. Nat Rev Cancer 2017;17:425–440

Work-up

History and physical examination

  1. Spleen size by palpation (cm below left costal margin)

  2. Sites of extramedullary involvement other than hepatosplenomegaly

Laboratory studies

  1. CBC and leukocyte differential, complete metabolic panel, phosphorus, magnesium, uric acid, and LDH

  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. Baseline 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...

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