JCO Early Release, published online ahead of print Jul 6 2009
Journal of Clinical Oncology, 10.1200/JCO.2008.20.2960
Myeloablative Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: Analysis of Graft Sources and Long-Term Outcome
Michael B. Tomblyn, Mukta Arora, K. Scott Baker, Bruce R. Blazar, Claudio G. Brunstein, Linda J. Burns, Todd E. DeFor, Kathryn E. Dusenbery, Dan S. Kaufman, John H. Kersey, Margaret L. MacMillan, Philip B. McGlave, Jeffrey S. Miller, Paul J. Orchard, Arne Slungaard, Marcie R. Tomblyn, Gregory M. Vercellotti, Michael R. Verneris, John E. Wagner, and Daniel J. Weisdorf*
From the Department of Therapeutic Radiology and Radiation Oncology; and the Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN.
* To whom correspondence should be addressed. E-mail: email@example.com
: Analysis of hematopoietic cell transplantation (HCT)for high-risk or recurrent acute lymphoblastic leukemia (ALL)using different donor sources is confounded by variable conditioningand supportive care.
Patients and Methods: We studied 623 consecutiveALL myeloablative HCT (1980 to 2005). Donors were autologous(n = 209), related (RD; n = 245), unrelated (URD; n = 100),and umbilical cord blood (UCB; n = 69).
Results: After medianof 8.3 years of follow-up, 5-year overall survival (OS), leukemia-freesurvival (LFS), and relapse were 29% (95% CI, 26% to 32%), 26%(95% CI, 23% to 29%), and 43% (95% CI, 39% to 47%), respectively.Treatment-related mortality (TRM) at 2 years was 28% (95% CI,25% to 31%). Mismatched URD sources yielded higher TRM (relativerisk [RR], 2.2; P < .01) and lower OS (RR, 1.5; P = .05)than RD or UCB HCT. Autografting yielded significantly morerelapse (68%; 95% CI, 59% to 77%; P < .01) and poorer LFS(14%; 95% CI, 10% to 18%; P = .01). HCT in first complete remission(CR1) yielded significantly better outcomes than later HCT.In a 1990 to 2005 allogeneic CR1/second complete response cohort,5-year OS, LFS, and relapse rates were 41% (95% CI, 35% to 47%),38% (95% CI, 32% to 44%), and 25% (95% CI, 19% to 31%), respectively;2-year TRM was 34% (95% CI, 28% to 40%). With RD, well-matchedURD and UCB sources, 5-year LFS was 40% (95% CI, 31% to 49%),42% (95% CI, 14% to 70%), and 49% (95% CI, 34% to 64%), respectively,while relapse was 31% (95% CI, 22% to 40%), 17% (95% CI, 0%to 37%), and 27% (95% CI, 13% to 41%). Acute graft-versus-hostdisease was associated with fewer relapses. Since 1995, we notedprogressive improvements in OS, LFS, and TRM.
Conclusion: Allogeneic,but not autologous, HCT for ALL results in durable LFS. Importantly,HCT using UCB led to similar outcomes as either RD or well-matchedURD. HCT in early remission can best exploit the potent antileukemicefficacy of allografting from UCB, RD, or URD sources.