Article

Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison.

Peking University People's Hospital, Institute of Hematology, Beijing, People's Republic of China.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.15). 06/2011; 17(6):821-30. DOI: 10.1016/j.bbmt.2010.08.023
Source: PubMed

ABSTRACT The outcomes of an historic comparison of 117 consecutive, high-risk, acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) from HLA-mismatched/haploidentical donors (HID, n = 81) or HLA-identical sibling donors (ISD, n = 36) without the use of in vitro T cell depletion (TCD), between the period of January 2005 and April 2009 were compared. Full engraftment was achieved in 98% of patients in the HID group and 97% in the ISD group. The cumulative incidences of grades II-IV acute graft-versus-host disease (aGVHD) in the HID and ISD cohorts were 49% and 24%, respectively (P = .014) with a relative risk (RR) of 2.99 (1.25-7.21) (P = .014). The incidence of chronic GVHD (cGVHD) did not differ significantly between the 2 cohorts. The 2-year cumulative incidence of relapse was significantly lower in HID (26%) than in ISD patients (49%) (P = .008). The 2-year cumulative incidence of nonrelapse mortality (NRM) was comparable in recipients of HID (34%) and ISD grafts (38%) (P = .85). The 3-year probability of overall survival (OS) was higher in HID patients (42%) than in ISD (20%) (P = .048) patients. Our comparisons suggest that HID transplants can achieve a stronger graft-versus-leukemia (GVL) effect than ISD for high-risk acute leukemia patients.

0 Bookmarks
 · 
65 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Haploidentical hematopoietic stem cell transplantation offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an alternative treatment for patients with hematologic malignancies who do not have a completely human leukocyte antigen matched sibling or who require urgent transplantation. Unfortunately, high incidence of life-threatening infections and leukemia relapse resulting from slow immune reconstitution remain the two most frequent causes of mortality in haploidentical transplant settings, particularly for patients who received extensively T-cell depleted mega-dose CD34+ allografts. This review summarizes advances in immune recovery after haploidentical hematopoietic stem cell transplantation, focusing on the immune subsets that are likely to have the greatest impact on clinical outcomes. The progress that has been made in accelerating immune reconstitution using different strategies after haploidentical transplantation is also discussed. It is our belief that a predictive immune subset guided strategy to improve immune recovery might represent a future clinical direction.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2013; · 3.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The fundamental obstacle to the successful application of partially HLA-mismatched related donor, or HLA-haploidentical stem cell transplantation, is the strength of the host and donor T-cell response to allogeneic HLA molecules, which results in increased incidences of graft failure, GVHD, and nonrelapse mortality. The holy grail of haplo-SCT is to mitigate host-versus-graft and graft-versus-host responses while preserving immune responses to infection and the patient's malignancy. Two strategies have been taken to achieve this goal. The first strategy is to supplement a T cell-depleted graft with pathogen-specific T cells or populations of T cells in which alloreactivity can be controlled. The second strategy is to eliminate alloreactive T cells selectively from a T cell-replete graft. Substantial progress has been made with both approaches so that the safety of haplo-SCT now approaches that of SCT using grafts of umbilical cord blood or from HLA-matched donors. In light of the rapid and near universal availability of HLA-haploidentical related donors, it should now be possible to identify and mobilize a donor for every patient referred for allogeneic SCT. Prospective comparisons between haploidentical SCT and unrelated donor SCT should be performed to identify the most efficacious approach to alternative donor transplantation.
    Hematology 01/2012; 2012:230-6. · 1.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most patients who require allogeneic stem cell transplantation do not have a matched sibling donor, and many patients do not have a matched unrelated donor. In an effort to increase the applicability of transplantation, alternative donors such as mismatched adult unrelated donors, haploidentical related donors, and umbilical cord blood stem cell products are frequently used when a well matched donor is unavailable. We do not yet have the benefit of randomized trials comparing alternative donor stem cell sources to inform the choice of donor; however, data exist to allow some inferences based on existing observational and phase II studies. All three alternative donor sources can provide effective lymphohematopoietic reconstitution, but time to engraftment, graft failure rate, graft versus host disease, transplant-related mortality, and relapse risk vary by donor source. These factors all contribute to survival outcomes and an understanding of them should help guide clinicians when choosing amongst alternative donor sources when a matched related or matched unrelated donor is not available.
    Blood 06/2014; · 9.78 Impact Factor