Stem cell transplantation in patients with chronic myelogenous leukemia: when should it be used?
Hematopoietic stem cell transplantation has been a cornerstone of therapy for chronic myelogenous leukemia (CML) for more than 15 years and is still a standard treatment option for patients with CML. The advent of imatinib mesylate, an inhibitor of the molecular defect driving CML, the BCR-ABL tyrosine kinase, has rewritten treatment algorithms for this disease and has shifted focus away from allografting. Despite advances in stem cell transplantation, such as broader availability with the use of modified conditioning regimens, use of allografting has diminished. Also, the nearly universal patient exposure to imatinib or other kinase inhibitors before transplantation may affect the biology of the disease that is currently being treated with an allograft and ultimately may affect outcomes. Exceedingly high rates of meaningful and stable response with longer follow-up continue to drive enthusiasm for imatinib use, and understanding of resistance mechanisms has driven rapid investigation of second-generation tyrosine kinase inhibitors to address imatinib failure and suboptimal response. In most patients, imatinib reduces CML to a minimal residual disease state in which options to further deepen remission, such as immunotherapy, are sought; monitoring techniques and interpretation of response advance in parallel to meet demands; and uncertainty remains as a new natural history of CML is defined in an era of kinase inhibitor therapy. This review summarizes the state of transplant and nontransplant therapy for CML and discusses the decision making for patients with an aim to optimize the use of our best therapies for CML in an era of uncertainty.
Mauro
Michael J
MJ
Center for Hematologic Malignancies, Oregon Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, UHN73C, Portland, OR 97239, USA. maurom@ohsu.edu
Maziarz
Richard T
RT
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D018579:Patient Selection; D010879:Piperazines / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D011743:Pyrimidines / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate