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Chronic Myelogenous Leukemia: Biology and Therapy

Stefan Faderl, MD; Moshe Talpaz, MD; Zeev Estrov, MD; and Hagop M. Kantarjian, MD
[+] Article and Author Information

From the University of Texas M.D. Anderson Cancer Center, Houston, Texas.


Requests for Reprints: Hagop M. Kantarjian, MD, Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Current Author Addresses: Drs. Faderl and Kantarjian: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Drs. Talpaz and Estrov: Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, 1515Holcombe Boulevard, Houston, TX 77030.


Ann Intern Med. 1999;131(3):207-219. doi:10.7326/0003-4819-131-3-199908030-00008
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Chronic myelogenous leukemia is a myeloproliferative disorder. It is characterized by a biphasic or triphasic clinical course in which a benign chronic phase is followed by transformation into an accelerated and blastic phase. On a cytogenetic and molecular level, most patients with chronic myelogenous leukemia demonstrate BCR-ABL fusion genes in hematopoietic progenitor cells, which result from a reciprocal translocation between chromosomes 9 and 22; this translocation leads to a shortened chromosome 22, called the Philadelphia chromosome. Translation of the fusion products yields chimeric proteins of variable size that have increased tyrosinekinase activity. Conventional chemotherapy with hydroxyurea or busulfan can achieve hematologic control but cannot modify the natural disease course, which inevitably terminates in a rapidly fatal blastic phase. Since its introduction in the 1980s, allogeneic stem-cell transplantation has provided the groundwork for a cure of chronic myelogenous leukemia. However, few patients are eligible for this treatment because of donor availability and age restrictions. Therapy with interferon-α alone or in combination with cytarabine suppresses theleukemic clone, produces cytogenetic remissions, and prolongs survival. It is an effective alternative first-line treatment for patients ineligible for transplantation. New drugs active against chronic myelogenous leukemia may show increased activity in the transformed phases of the disease. Novel therapies and concepts are developing rapidly; targeted molecules are tyrosine kinases, ras, and messenger RNA through antisense oligonucleotides. Alternative transplantation options, such as stem cells from autologous sources and matched unrelated donors, are expanding. Immunomodulation by adoptive immunotherapy and vaccine strategies hold significant promise for the cure of chronic myelogenous leukemia.

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Figure.
Proposed treatment algorithm for patients with chronic myelogenous leukemia.

The choice of front-line therapy depends on the extent of treatment-related mortality. If treatment-related mortality is less than 20% (for example, in younger patients with matched related donors), stem-cell transplantation may be considered; if treatment-related mortality is 20% to 40%, interferon-α therapy (for example, in older patients with matched related donors), is appropriate. If the expected 1-year mortality rate with stem-cell transplantation exceeds 40% (for example, in the case of matched unrelated donor transplantations in older patients or transplantations with tissue from molecularly mismatched donors), stem-cell transplantation may be deferred until clear signs of disease acceleration appear. Patients may then be offered continuation of interferon-α-based therapies or other investigational therapies. CHR = complete hematologic response; CGR = cytogenic response; Ph = Philadelphia chromosome.

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