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

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.

Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation

“…Our previous study also suggested that in patients with refractory/relapsed acute leukemia, haploidentical HSCT was associated with a lower relapse rate (26% vs 49%, P = 0.008) and better overall survival (42% vs 20%, P = 0.048) than HLA-identical sibling HSCT. 29 Kanda et al 30 reported that for standard-risk acute leukemia, the incidence of relapse after HLA-identical sibling HSCT did not significantly differ from that after haploidentical HSCT (22% vs 15%; P = 0.25); in contrast, for high-risk acute leukemia, the incidence of relapse was 47% after HLA-identical sibling HSCT versus 19% after haploidentical HSCT (P = 0.004). However, the underlying biological mechanism needs to be explored further.…”

Haploidentical hematopoietic SCT may be superior to conventional consolidation/maintenance chemotherapy as post-remission therapy for high-risk adult ALL

“…6,18,19 Furthermore, our previous study demonstrated that haplo-HSCT might be associated with a superior GVL effect than HLA-identical sibling donor grafts in high-risk acute leukemia. 20 In addition, the decreased relapse rate may be owing to some preemptive strategies for preventing relapse, such as risk-stratified DLI 10 or low-dose IL-2, 8 which is administered at our center, and early prophylactic imatinib for Phpositive ALL patients after transplantation. 7,21 The toxicity of transplantation in previous studies may explain why a reduced relapse rate did not translate to improved survival.…”

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission

“…19 This suggests that HRD transplantations can achieve a stronger GVL effect, which may contribute to the superior survival of AML patients with unfavorable cytogenetics. Secondly, the patients in the present study all achieved CR1 through 1-2 courses of induction chemotherapy and received 2-4 courses of consolidation therapy before transplantation.…”

“…In a historic comparison of 117 consecutive, high-risk acute leukemia patients undergoing HSCT from HLA-mismatched/haploidentical donors (HIDs; n ϭ 81) or HLA-identical sibling donors (ISDs; n ϭ 36) without in vitro T-cell depletion, Wang et al found that the 3-year OS rate was higher in HID patients (42%) than in ISD (20%) patients (P ϭ .048). 19 The investigators suggested that HID transplantations can achieve a stronger GVL effect than ISD transplantation for high-risk acute leukemia patients.…”

“…15 Available data suggest that haploidentical HSCT is a feasible treatment option for high-risk AML patients who lack an HLA-matched donor. 10,[17][18][19] Researchers at Peking University developed the GIAC protocol, a novel approach to HLA-mismatched/haploidentical related donor HSCT (HRD-HSCT) without in vitro T-cell depletion. [11][12][13] (The GIAC protocol entails the following: treating donors with granulocyte colony-stimulating factor [G-CSF] to induce donor immune tolerance, intensified immunologic suppression to both promote engraftment and to prevent GVHD, antithymocyte globulin [ATG] was included for the prophylaxia of GVHD and graft rejection, and combination of G-CSF-primed bone marrow harvest [G-BM] and G-CSF-mobilized peripheral blood stem cell harvest [G-PB] as the source of stem cell grafts.)…”