Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome

J Clin Oncol. 2009 Aug 1;27(22):3634-41. doi: 10.1200/JCO.2008.20.2960. Epub 2009 Jul 6.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Graft Rejection
  • Graft Survival
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / mortality
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery*
  • Probability
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors
  • Tissue Donors
  • Transplantation Conditioning*
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult