Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Apr 2014
Multicenter Study Clinical TrialUnrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells.
Allogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). ⋯ Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward.
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Biol. Blood Marrow Transplant. · Apr 2014
Effect of ABO blood group incompatibility on the outcome of single-unit cord blood transplantation after myeloablative conditioning.
ABO blood group incompatibility between donor and recipient has been associated with poor transplant outcomes in allogeneic hematopoietic stem cell transplantation. However, its effect on the outcome of cord blood transplantation (CBT) has yet to be clarified. ⋯ Nevertheless, there was no increase in graft-versus-host disease, transplant-related mortality, and overall mortality after ABO-incompatible CBT. These data suggested that donor-recipient ABO incompatibility does not have a significant impact on outcome after myeloablative CBT for hematological malignancies.
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Biol. Blood Marrow Transplant. · Apr 2014
HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia.
We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given T cell-depleted, CD34(+) positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. ⋯ The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of T cell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.
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Biol. Blood Marrow Transplant. · Apr 2014
Long-term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation.
Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long-lasting immune deficiency. Sixty-six patients who underwent a first transplantation from either UCB (n = 30) or 9/10 MMUD (n = 36) and who survived beyond 3 months were evaluated. Immune reconstitution was prospectively assessed at sequential time points after transplantation. ⋯ To the contrary, high percentage of effector- and late effector-memory subsets at 3 months among the CD8(+) T cell compartment predicted higher risks for viral infections. Patients who underwent transplantation from alternative donors represent a population with very high risk of infection. Detailed phenotypic analysis of immune reconstitution may help to evaluate infection risk and to adjust infection prophylaxis.
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Biol. Blood Marrow Transplant. · Mar 2014
Multicenter StudyNOD2/CARD15 single nucleotide polymorphism 13 (3020insC) is associated with risk of sepsis and single nucleotide polymorphism 8 (2104C>T) with herpes viruses reactivation in patients after allogeneic hematopoietic stem cell transplantation.
Three NOD2 polymorphisms (single nucleotide polymorphism [SNP]8 [2104C>T, Arg702Trp], SNP12 [2722G>C, Gly908Arg], and SNP13 [3020insC, Leu1007 fsins C]), identified as disease-associated variants in Crohn's disease, have recently been suggested as gene markers of the outcome of hematopoietic stem cell transplantation (HSCT). In the present multicenter study of 464 donor-recipient pairs, we focused on the effect of NOD2 mutation(s) on the risk of infections and acute graft-versus-host disease (aGVHD). The presence of SNP13 in recipients, donors, or both was more frequently seen in patients having sepsis than in those lacking sepsis (9 of 48 versus 33 of 386, P = .046). ⋯ In conclusion, SNP8 positivity in donors or recipients makes patients more prone to Herpes viruses reactivation and bacteremia but not to sepsis. Septic complications were associated with SNP13 polymorphism. SNP8 in donors constitutes a risk factor of severe aGVHD, but only if patients received transplants from unrelated donors and received ATG as part of a conditioning regimen.