Allogeneic stem cell transplantation for chronic myeloid leukemia resistant to tyrosine kinase inhibitors.
Allogeneic hematopoietic stem cell transplantation (HSCT) is well-established as a potentially curative treatment for patients who have chronic myeloid leukemia. The success of imatinib and other tyrosine kinase inhibitors (TKI) as initial therapy has changed the treatment paradigm for this disease. Allogeneic hematopoietic transplants are now reserved for patients whose disease does not respond optimally to TKI treatment. Patients whose disease does not have an optimal response to imatinib may respond to a second-generation TKI, dasatinib or nilotinib, and many achieve major or complete molecular and cytogenetic responses. The indication for allogeneic HSCT versus continued second-line therapy is not well-defined and is the subject of ongoing study. There has been continued progress in reducing the toxicity and risks of HSCT with development of reduced-intensity regimens; transplants can be routinely performed in patients up to the age of 75 years who are in fair general medical condition. Transplantation results from unrelated donors have improved, with survival rates similar that achieved with matched siblings. Results with haploidentical and cord blood transplants have markedly improved, and should be considered for patients lacking a matched donor. Allogeneic hematopoietic transplants have the best chance to be curative in patients with chronic phase that is under hematologic control with 80% disease-free survival; patients progressing to the accelerated phase or blast crisis have a much poorer prognosis. Thus, HSCT should be considered for patients with imatinib failure. Patients receiving second-line TKI therapy must be closely monitored and referred for transplantation if a complete cytogenetic response and major molecular response is not achieved. HSCT should be performed if feasible in patients without a continued response to TKI treatment.
Department of Stem Cell Transplantation and Cellular Therapy and Leukemia, University of Texas-MD Anderson Cancer Center, Houston, TX 77030, USA. rchampli@mdanderson.org
Richard
R
Champlin
Elias
E
Jabbour
Partow
P
Kebriaei
Paolo
P
Anderlini
Borje
B
Andersson
Marcos
M
de Lima
D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D014184:Transplantation, Homologous
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases