Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts.
Abstract
We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor.
Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Chair of Hematology, University of Genova, Italy.Division of Clinical Hematology, IRCCS San Martino IST, Genova, Italy.Chair of Medical Statistics, University of Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy.Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy. Electronic address: andrea.bacigalupo@hsanmartino.it. MeSH
AdolescentAdultAgedCord Blood Stem Cell TransplantationFemaleGene ExpressionGraft vs Host DiseaseHLA AntigensHaplotypesHematologic NeoplasmsHematopoietic Stem Cell TransplantationHistocompatibility TestingHumansImmunosuppressive AgentsMaleMiddle AgedMyeloablative AgonistsProspective StudiesRecurrenceSiblingsSurvival AnalysisTransplantation ConditioningTransplantation, HomologousUnrelated Donors
Pub Type(s)
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't