Current Status of Treatment for Chronic Myelogenous Leukemia

Kathryn S. Kolibaba, MD, Brian J. Druker, MD

Disclosures
In This Article

Abstract and Introduction

Abstract

Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22 that produces the Philadelphia chromosome. CML is characterized by marked proliferation of myeloid cells that mature normally. Invariably there is disease progression, with loss of the capacity for terminal differentiation by the hematopoietic stem cell, resulting in an acute leukemia.

Treatment options have become more complex in recent years, with allogeneic bone marrow transplantation still the only curative option. Improvements in treatment-related toxicity now make transplantation of older patients and the use of matched unrelated volunteer donors feasible. However, either due to age or lack of a suitable donor, allogeneic bone marrow transplantation is still not possible for the vast majority of CML patients.

Recent data show that interferon-alpha prolongs life in CML patients, as compared to hydroxyurea, the former cornerstone of therapy. The role of other treatment approaches, such as autologous bone marrow transplantation, has yet to be determined in clinical trials. New therapies based on the causative molecular abnormality of CML are showing great promise.

Introduction

Chronic myelogenous leukemia (CML) accounts for 15%-20% of cases of adult leukemia, with an incidence of 1 to 1.5 cases per 100,000 population.[1] CML is a disease of older adults, with a median age at diagnosis of 50 years. Characterized by an initial, relatively asymptomatic, stable phase of unpredictable duration, CML invariably terminates in a lethal acute leukemia.

Treatment options for patients with CML (reviewed in Kantarjian and Talpaz[2]) continue to expand, but allogeneic bone marrow transplantation remains the only curative therapy for CML. Unfortunately, donor availability and patient age limit the feasibility of allografting to approximately 35% of patients affected with CML.[3] The appeal of bone marrow transplantation is also limited by the risk of early death associated with the procedure, which increases with recipient age and degree of donor mismatch. However, other treatment strategies, albeit noncurative, are available for the majority of patients with CML, and there is now consensus that interferon-alpha is not only superior to hydroxyurea, but also prolongs life.

This article will first review the clinical presentation, natural history, and pathobiology of CML. Prognostic determinants for CML patients in the context of a growing array of treatment options will then be discussed, and an algorithm for treatment will be proposed. Finally, promising agents and treatment modalities on the horizon will be described.

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