Chronic Myelogenous Leukemia (CML) Guidelines

Updated: May 23, 2021
  • Author: Emmanuel C Besa, MD; Chief Editor: Sara J Grethlein, MD, FACP  more...
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Guidelines

Guidelines Summary

Guidelines contributor:  Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

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

  • National Comprehensive Cancer Network (NCCN) [21]
  • European Society of Medical Oncology (ESMO) [22]
  • European LeukemiaNet (ELN) [23]

For chronic-phase CML, treatment recommendations are as follows:

  • All of the guidelines recommend the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, or dasatinib as first-line treatment for CML; NCCN also includes bosutinib, and ESMO notes that other strategies include using higher doses of imatinib or combining a TKI with an additional agent, such as interferon-α.

  • All the guidelines agree that the selection of first-line TKI therapy should be based on the patient's risk score, ability to tolerate therapy, and comorbid conditions and the adverse effect profile of the TKI

  • In case of intolerance, patients can be switched to another TKI; ESMO and ELN list bosutinib as an option in this setting

  • All TKIs can be used as second-line treatment; doses may differ in the second- line setting, depending on the agent chosen

  • BCR-ABL kinase domain mutation analysis, evaluation of drug interactions, and compliance to therapy are recommended before the start of second-line TKI therapy.

  • Ponatinib is an option for patients with T315I mutation and for those with disease that has not responded to several TKIs.

  • Allogeneic 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, bosutinib, ponatinib).

  • 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

NCCN,  ELN, and ESMO guidelines recommend the following tests for monitoring response to TKI therapy [21, 22] :

  • Bone marrow cytogenetics

  • Quantitative reverse transcription polymerase chain reaction (qPCR) standardized by International Scale (IS)

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 [21] :

  • 3 months: BCR-ABL1 transcripts ≤10% by qPCR 

  • 6 months: BCR-ABL1 transcripts ≤10% by qPCR 

  • 12 months: ≤1% BCR-ABL1

  • 15 months: ≤ 1% BCR-ABL1 

  • After BCR-ABL1 (IS) ≤1% (> 0.1%–1%) has been achieved, every 3 months for 2 years and every 3–6 months thereafter; if there is 1-log increase in BCR-ABL1 transcript levels with major molecular response, qPCR should be repeated in 1-3 months

European LeukemiaNet

The optimal responses to first-line treatment are as follows [23] :

  • 3 months: Philadelphia chromosome positive (Ph+)  ≤35%, and/or BCR-ABL1≤10%

  • 6 months: : PH+ 0%, and/or BCR-ABL1 < 1%

  • 12 months: BCR-ABL1≤0.1%

European Society for Medical Oncology (ESMO)

The optimal responses to first-line treatment are as follows [22] :

  • 3 months: Ph+ ≤95%, or BCR-ABL< 10%

  • 6 months: Ph+ ≤35%, or BCR-ABL < 10%

  • 12 months: Ph+ 0, or BCR-ABL ≤1%