Originally published as JCO Early Release 10.1200/JCO.2008.20.2960 on July 6 2009

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Myeloablative Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: Analysis of Graft Sources and Long-Term Outcome

From the Department of Therapeutic Radiology and Radiation Oncology; and the Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN.

Corresponding author: Daniel J. Weisdorf, MD, University of Minnesota, MMC 480, 516 Delaware St., SE, Minneapolis, MN 55455; e-mail: weisd001{at}umn.edu.

Purpose Analysis of hematopoietic cell transplantation (HCT) for high-risk or recurrent acute lymphoblastic leukemia (ALL) using different donor sources is confounded by variable conditioning and supportive care.

Patients and Methods We studied 623 consecutive ALL 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 median of 8.3 years of follow-up, 5-year overall survival (OS), leukemia-free survival (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 (relative risk [RR], 2.2; P < .01) and lower OS (RR, 1.5; P = .05) than RD or UCB HCT. Autografting yielded significantly more relapse (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-matched URD 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-host disease was associated with fewer relapses. Since 1995, we noted progressive 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-matched URD. HCT in early remission can best exploit the potent antileukemic efficacy of allografting from UCB, RD, or URD sources.

Presented in part at Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, 2007.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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