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.

Lymphocyte subset reconstitution after unrelated cord blood or bone marrow transplantation in children

“…Successful immune reconstitution is predicted by the antigen-specific response and not only by the presence of T lymphocytes. There is probably not a complete correlation between the count of each lymphocyte subset and the presence or absence of antigen-specific response, but naïve T lymphocytes present in CB are able to contribute to the generation of antigen-specific T lymphocyte immunity early after transplantation Parkman et al, 2006). Indeed we observed no difference concerning incidence of CMV infection after UCBT or UBMT.…”

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor

“…Early appearance of T cells specific for different herpes viruses detected by a different methodology has been described in recipients of CBTs, even in the absence of clinical evidence of infection, and has been correlated with higher GVT effect. [18][19][20] Although we do not have data on chimerism specific for circulating NK cells within the initial 3 months, as patients initially develop double TPD/CB chimerism, both in circulating granulocytes and mononuclear cells that evolves to full CB chimerism within 3 months, they could initially have NK cells derived from the TPD. In case of killer cell Ig-like receptor incompatibility with the recipient such cells could provide some degree of NK cell-dependent innate immune protection that might contribute to the GVT effect.…”

Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation

“…6,[12][13][14] This more profound in vivo depletion may be due to the fact that ATG is produced in rabbits using infant human thymus, which may result in more antibodies against naive receptors, which are more likely to be present on cord blood T cells. 15,16 Successful IR following HCT is associated with improved chance of survival following HCT, 9,11,15,17,18 making efforts to improve IR imperative. Strategies to enhance IR may include optimizing the dosing and thereby the exposure to ATG.…”