Treatment options for chronic myeloid leukemia: imatinib versus interferon versus allogeneic transplant.
OBJECTIVE
This review considers recent developments in the treatment of chronic myeloid leukemia with attention to current data evaluating the relative roles of imatinib mesylate, interferon-alpha, and allogeneic blood or marrow transplantation. Additionally, the review discusses advances in the basic understanding of the mechanisms by which these three different therapies function against chronic myeloid leukemia.


RESULTS
Long-term follow-up has found that interferon-alpha was able to produce complete cytogenetic remission in15 to 25% of patients, with some of these patients achieving a molecular remission. Some patients who achieve a complete cytogenetic remission also achieve long-term disease-free survival and possibly cure. Imatinib has produced remarkable hematologic and cytogenetic responses in newly treated and in interferon-alpha-refractory patients, yet there are no long-term survival data at this point. Some laboratory findings imply that imatinib may primarily affect mature chronic myeloid leukemia progenitors and not chronic myeloid leukemia stem cells, leaving doubt that the improved rate of complete cytogenetic remissions will result in increased overall survival. Other clonal cytogenetic abnormalities have also been reported in the Philadelphia chromosome-negative cells present in complete cytogenetic remissions to imatinib. The use of donor lymphocytes infusion (DLI) continues to treat relapsed chronic myeloid leukemia effectively after allogeneic blood or marrow transplantation whereas the use of nonmyeloablative therapy has effectively reduced transplant-related mortality.


CONCLUSIONS
Patients with chronic myeloid leukemia now have several potential treatment options from which to choose. Imatinib mesylate currently provides excellent hematologic and cytogenetic response rates with minimal toxicity. However, long-term data of efficacy is lacking. Emerging evidence that imatinib rarely leads to molecular complete remission and that many patients are still at risk of relapse and other clonal disorders is concerning and suggest the possibility that imatinib's early high response rates may not translate into survival advantage. Interferon-alpha continues to be effective therapy for many patients and, along with blood or marrow transplantation, is proved to prolong survival. The impacts of both are in part limited because of their toxicity profiles. Ongoing laboratory investigations and clinical trials remain paramount to providing the best treatment approach for our patients with chronic myeloid leukemia.
Angstreich
Greg R
GR
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Room 207, Baltimore, MD 21231, USA.
Smith
B Douglas
BD
Jones
Richard J
RJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D016026:Bone Marrow Transplantation; D003657:Decision Making; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate