Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.
Bibliographical noteFunding Information:
This study was supported by contracts from the National Heart, Lung and Blood Institute (N01-HB-67135 to RP, KIW, BM; N01-HB-67132 to GC, SLC, NAK; N01-HB-67139 to JEW; N01-HB-67138 to JK; and N01-HB-67113 to EG) and grant P01-CA100265 (RP). We are indebted to Manuela Alvarez-Wilson and Angela Norman for assistance in the preparation of the manuscript.
- Immune reconstitution
- Tumor immunity