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Chronic Myelogenous Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Accelerated-Phase Chronic Myelogenous Leukemia (CML)

Treatment Options for Accelerated-Phase CML

  1. Allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT). In 132 patients with accelerated-phase CML, a cohort study compared imatinib as first-line therapy versus allogeneic SCT; with a median follow-up of 32 months, overall survival was improved using allogeneic SCT for the Sokal high-risk patients (100% vs. 17.7%; P = .008).[1][Level of evidence: 3iiiA] Sokal low- and intermediate-risk patients showed no survival differences starting with either approach. Induction of remission using a tyrosine kinase inhibitor followed by an allogeneic SCT, when feasible, is a standard approach for patients with accelerated-phase CML.[1]
  2. Imatinib mesylate. Among 176 patients with accelerated-phase CML, the complete hematologic response was 82%, and the complete cytogenetic response was 43%; with a median follow-up of 41 months, the estimated 4-year survival was 53%.[2] Other tyrosine kinase inhibitors need to be evaluated as first-line therapy in accelerated-phase CML.
  3. Interferon alpha.[3] Although the response rate is lower for accelerated-phase disease than it is for chronic-phase disease, durable responses and suppression of cytogenetic clonal evolution have been reported.[3,4] When cytarabine was added to interferon alpha, in comparison to historical controls of interferon alone, the response rate and 3-year survival appeared to be improved in late-stage patients.[4][Level of evidence: 3iiiA]
  4. High-dose cytarabine.[5]
  5. Hydroxyurea.
  6. Busulfan.
  7. Supportive transfusion therapy.

Patients with accelerated-phase CML show signs of progression without meeting the criteria for blast crisis (acute leukemia). Symptoms and findings include the following:

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  • Increasing fatigue and malaise. (Refer to the PDQ summary on Fatigue for more information.)
  • Progressive splenomegaly.
  • Increasing leukocytosis and/or thrombocytosis.
  • Worsening anemia.

Bone marrow examination shows increasing blast cell percentage (but ≤30%) and basophilia. Additional cytogenetic abnormalities occur during the accelerated phase (trisomy 8, trisomy 19, isochromosome 17Q, p53 mutations or deletions), and the combination of hematologic progression plus additional cytogenetic abnormalities predicts for lower response rates and a shorter time-to-treatment failure on imatinib mesylate.[6] At 1 year after the start of imatinib, the failure rate is 68% for patients with both hematologic progression and cytogenetic abnormalities, 31% for patients with only hematologic progression, and 0% for patients with cytogenetic abnormalities only. Before the availability of imatinib, the median survival time of accelerated-phase CML patients was less than 1 year.[6]

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