CML


Expand All | Collapse All

  • Clinical

    • elderly
    • leukocytosis, basophilia
    • blast phase can involve nodes and soft tissue

  • Therapy & monitoring

    • tx: HCT (curative), TKIs, cytotoxic agents (palliative)
      • HCT: for young pts with suitable donor, those resistant to TKIs or with blast phase
      • TKIs: for most pts
      • cytotoxic agents: hydroxyurea, interferon alpha +/- cytarabine, busulfan
    • monitoring: cytogenetics of marrow biopsies, PCR on peripheral blood
    • response
      • hematologic response
        • WBC < 10k
        • lack immature granulocytes
        • < 5% basophils
        • plt < 450
        • spleen not palpable
      • cytogenetic response
        • complete response = no Ph chr detected by metaphase banding analysis of 20+ cells
        • alternatively: < 1% BCR-ABL1 by FISH of at least 200 cells
        • other: no response (> 95% Ph chr), minimal (66-95%), minor (36-65%), major (1-35%)
      • molecular response
        • international scale = ratio of BCR-ABL1 to control (ABL1), on log scale
        • MR2: 2 log reduction (1%), corresponds to complete cytogenetic response
        • MR3: 3 log reduction (0.1%), aka major molecular response
        • MR4: 4 log reduction (0.01%)
        • MR4.5: 0.0032%, not detectable in 32,000 control transcripts
    • residual disease clues
      • hypercellularity
      • clusters of dwarf megakaryocytes, gaucher like histiocytes
      • basophilia

  • Phases

    • chronic: < 2% blasts
    • accelerated: 10-19% blasts
    • blast: > 20% blasts

  • Morphology

    • neutrophils of varying stages of maturation
    • small hypolobated megakaryocytes
    • pseudo-gaucher cells, sea blue histiocytes

  • Molecular

    • BCR-ABL1, t(9;22)(q34;q11.2) (> 90% of cases)
    • BCR on chr 22, breaks apart at MBCR region (exon 12-16)
    • ABL on chr 9
    • p210 is resulting fusion protein that has increased tyrosine kinase activity
    • alternative: BCR breaks at mBCR (exon 1-2) -> p190 -> Ph+ ALL, CML with increased monocytes (CMML-like)
    • alternative: BCR breaks at uBCR (exon 17-20) -> p230 -> can have prominent neutrophil maturation, thrombocytosis
    • cryptic translocations: detectable by FISH, but not karyotype
    		•