Chronic Myelogenous Leukemia (CML) Guidelines 

Updated: Dec 23, 2016
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Management of Chronic Myelogenous Leukemia (CML)

Guidelines for the management of chronic myelogenous leukemia (CML) have been issued by the following organizations:

  • National Comprehensive Cancer Network (NCCN) [1]
  • European Society of Medical Oncology (ESMO) [2]
  • European LeukemiaNet (ELN) [3]

For chronic-phase CML, all the guidelines recommend the following:

  • Any of three tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, or dasatinib) are the first-line treatment for CML
  • In case of intolerance, patients can be switched to another TKI or bosutinib
  • All three TKIs can be used as second-line treatment; doses may differ in the second- line setting, depending on the agent chosen
  • Hematopoietic stem cell transplantation (HSCT) should be considered in the case of failure of two TKIs

For accelerated-phase CML, all the guidelines recommend the following:

  • TKI (imatinib, nilotinib, dasatinib or bosutinib).
  • Choice of TKI is based on prior therapy and/or BCR-ABL kinase domain mutation status
  • Recommended doses of imatinib, nilotinib, and dasatinib are higher for accelerated phase than for chronic phase
  • If resistance and/or intolerance to two or more TKIs occurs, consider omacetaxine
  • Consider HSCT, based on treatment response and patient age

For blast-phase CML, all the guidelines recommend the following:

  • HSCT, preferably after response to induction therapy
  • Patients in lymphoid blast phase can be treated with acute lymphoblastic leukemia (ALL) induction chemotherapy regimens in combination with a TKI
  • Patients in myeloid blast crisis can be treated with acute myeloid leukemia (AML) induction chemotherapy regimens in combination with a TKI

Monitoring

National Comprehensive Cancer Network (NCCN), European LeukemiaNet (ELN), and European Society of Medical Oncology (ESMO) guidelines recommend the following tests for monitoring response to tyrosine kinase inhibitor (TKI) therapy:

  • Bone marrow cytogenetics
  • Quantitative reverse transcription polymerase chain reaction (QPCR)

The three guidelines vary in their recommendations regarding response to first-line treatment, as outlined below.

NCCN Recommendations

The desired responses to first-line treatment are as follows:

  • 3 months: BCR-ABL1 transcripts ≤10% by QPCR or partial cytogenetic response (PCyR) on bone marrow cytogenetics
  • 6 months: BCR-ABL1 transcripts ≤10% by QPCR or ≥ PCyR on bone marrow cytogenetics
  • 12 months: Complete cytogenetic response (CCyR) on bone marrow cytogenetics (if neither CCyR nor major molecular response [MMR] has been previously achieved)
  • 18 months: CCyR on bone marrow cytogenetics (if not in MMR and lack of CCyR at 12 months)
  • Any time: Stable or improving MMR

European LeukemiaNet

The optimal responses to first-line treatment are as follows:

  • 3 months: Ph+≤35%, and/or BCR-ABL1≤10%
  • 6 months: : PH+ 0%, and/or BCR-ABL1 < 1%
  • 12 months: BCR-ABL1≤0.1%

European Society of Medical Oncology (ESMO)

The optimal responses to first-line treatment are as follows:

  • 3 months: Philadelphia chromosome positive (Ph+) ≤95%, or BCR-ABL< 10%
  • 6 months: Ph+ ≤35%, or BCR-ABL < 10%
  • 12 months: PH+ 0, or BCR-ABL ≤1%