Treatment Options for Accelerated-Phase CML
- Allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT). In 132 patients with accelerated-phase chronic myelogenous leukemia (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).[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.
- 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%. Other tyrosine kinase inhibitors need to be evaluated as first-line therapy in accelerated-phase CML.
- Interferon alpha. 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.[Level of evidence: 3iiiA]
- High-dose cytarabine.
- 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:
- 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. 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.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with accelerated phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Jiang Q, Xu LP, Liu DH, et al.: Imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in the accelerated phase. Blood 117 (11): 3032-40, 2011. [PUBMED Abstract]
- Kantarjian H, Talpaz M, O'Brien S, et al.: Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia--comparison with historic experience. Cancer 103 (10): 2099-108, 2005. [PUBMED Abstract]
- Cortes J, Talpaz M, O'Brien S, et al.: Suppression of cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. J Clin Oncol 16 (10): 3279-85, 1998. [PUBMED Abstract]
- Kantarjian HM, Keating MJ, Estey EH, et al.: Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine. J Clin Oncol 10 (5): 772-8, 1992. [PUBMED Abstract]
- Kantarjian HM, Talpaz M, Kontoyiannis D, et al.: Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor. J Clin Oncol 10 (3): 398-405, 1992. [PUBMED Abstract]
- O'Dwyer ME, Mauro MJ, Kurilik G, et al.: The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood 100 (5): 1628-33, 2002. [PUBMED Abstract]