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

Abstract

A B S T R A C T PurposeAnalysis 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 MethodsWe studied 623 consecutive ALL myeloablative HCT (1980HCT ( to 2005. Donors were autologous (n ϭ 209), related (RD; n ϭ 245), unrelated (URD; n ϭ 100), and umbilical cord blood (UCB; n ϭ 69). ResultsAfter 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 Ͻ .01) and lower OS (RR, 1.5; P ϭ .05) than RD or UCB HCT. Autografting yielded significantly more relapse (68%; 95% CI, 59% to 77%; P Ͻ .01) and poorer LFS (14%; 95% CI, 10% to 18%; P ϭ .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. ConclusionAllogeneic, 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.

Donor-specific differences in long-term outcomes of myeloablative transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia

“…23 In this report, B40% of patients were over 35 years (median age, 33 years; range, 16-59 years). In accordance with other studies, 20,34 our data also showed that older age was associated with higher NRM and lower survival. Thus, the relevance of age factor with regard to transplantation outcomes should be considered.…”

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…18 Previous studies had already demonstrated that results after related and unrelated allo-HSCT for adults with ALL were similar. [19][20][21] Allo-SCT from related or matched unrelated donors results in 5-year OS from 40-50% in high-risk patients. Autologous HSCT may be considered in patients lacking a donor, with similar results but higher relapse incidence.…”

Quantification of minimal residual disease levels by flow cytometry at time of transplant predicts outcome after myeloablative allogeneic transplantation in ALL

“…1 Results using alternative stem cell sources or alternative donors have improved in the last decade, and current outcomes after HSCT are strongly correlated with clinical disease status. [2][3][4][5] The optimal results in both children and adults are obtained when patients underwent HSCT at early stages of the disease as measured by conventional morphological remission. [5][6][7] Over the last decade, the concept of remission in ALL has evolved owing to use of molecular techniques and multiparameter flow cytometry (MFC) to more precisely track residual leukemic cells during chemotherapy treatment.…”