Accelerated-Phase Chronic Myelogenous Leukemia

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Treatment Options for Accelerated-Phase Chronic Myelogenous Leukemia

1. Bone marrow transplantation (BMT). Autologous BMT may return the patient to a chronic phase, which may be durable. Allogeneic BMT has the potential for cure, though results to date are poor.[1,2,3] Induction of remission with imatinib mesylate followed by allogeneic stem cell transplantation is under clinical evaluation.
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%.[4]
3. Interferon alpha.[5] 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.[5,6] 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.[6][Level of evidence: 3iiiA]
4. High-dose cytarabine.[7]
5. Hydroxyurea.
6. Busulfan.
7. Supportive transfusion therapy.

Patients with accelerated-phase chronic myelogenous leukemia (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.[8] 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.[8]

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.

References:

1. Martin PJ, Clift RA, Fisher LD, et al.: HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: analysis of survival and remission duration. Blood 72 (6): 1978-84, 1988.
2. Copelan EA, Grever MR, Kapoor N, et al.: Marrow transplantation following busulfan and cyclophosphamide for chronic myelogenous leukaemia in accelerated or blastic phase. Br J Haematol 71 (4): 487-91, 1989.
3. Reiffers J, Trouette R, Marit G, et al.: Autologous blood stem cell transplantation for chronic granulocytic leukaemia in transformation: a report of 47 cases. Br J Haematol 77 (3): 339-45, 1991.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.