title: Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.
abstract: 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.
authors.affiliation: Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, The Saban Research Institute, 4650 Sunset Boulevard, Mail Stop 62, Los Angeles, CA 90027, USA. rparkman@chla.usc.edu
authors.forename: Robertson
authors.initials: R
authors.lastname: Parkman
authors.forename: Geoff
authors.initials: G
authors.lastname: Cohen
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Carter
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Weinberg
authors.forename: Bernadette
authors.initials: B
authors.lastname: Masinsin
authors.forename: Eva
authors.initials: E
authors.lastname: Guinan
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D020127:Recovery of Function / Q000276:immunology*; D012008:Recurrence; D012074:Remission Induction; D012737:Sex Factors; D014184:Transplantation, Homologous