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: 3.4). 06/2011; 17(6):821-30. DOI: 10.1016/j.bbmt.2010.08.023
Source: PubMed


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.

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    • "A single-center study reported that unmanipulated myeloablative HSCT using the GIAC protocol has similar LFS/grade, III-IVaGVHD/extensive, chronic GVHD compared with HLA-matched sibling transplantation or matched unrelated donor transplantation [19,21]. The GIAC protocol also demonstrated improved GVL effects [22]. Also, modified haploidentical nonmyeloablative transplantation without T cell depletion and haploidentical PBSCT have been successfully launched as routine procedures in other centers in China [16,23]. "
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    ABSTRACT: Haploidentical stem cell transplantation is an attractive form of transplantation because of the immediate donor availability, ease of stem cell procurement, and the possibility to further collect donor cells for cellular therapy. Historically, maintaining T cells in the graft has been associated with very high rates of graft-versus-host-disease (GVHD), whereas T cell-depleted haploidentical transplantation has been limited by a higher incidence of graft rejection and nonrelapse mortality related to infectious complications as a result of delayed immune reconstitution posttransplantation. Recent approaches have attempted to eliminate the alloreactive T cells to prevent GVHD posttransplantation. Administration of high-dose cyclophosphamide early posttransplantation in combination with tacrolimus and mycophenolate mofetil has produced engraftment and GVHD rates similar to HLA-matched sibling transplants, suggesting that the most important barriers against successful haploidentical transplantation can be overcome. Future directions should focus on optimizing conditioning regimens for different diseases and prevention of disease relapse posttransplantation.
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