Scientific publications

Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC

Apr 1, 2022 | Magazine: Transplantation and Cellular Therapy

Rebeca Bailén  1 , María Jesús Pascual-Cascón  2 , Manuel Guerreiro  3 , Lucía López-Corral  4 , Anabelle Chinea  5 , Arancha Bermúdez  6 , Antonia Sampol  7 , Inmaculada Heras  8 , Estefanía García-Torres  9 , Melissa Torres  10 , José Rifón Roca  11 , Beatriz Herruzo  2 , Jaime Sanz  3 , Marta Fonseca  4 , Pilar Herrera  5 , Mercedes Colorado  6 , Leyre Bento  7 , Oriana López-Godino  8 , Carmen Martín-Calvo  9 , Paula Fernández-Caldas  10 , María Marcos-Jubilar  11 , Isabel Sánchez-Ortega  12 , Carlos Solano  13 , Víctor Noriega  14 , Karem Humala  15 , Gillen Oarbeascoa  1 , José Luis Díez-Martín  16 , Mi Kwon  17 , Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH)


Abstract

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation.

To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy.

Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249).

Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar.

Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors.

Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival.

CITATION  Transplant Cell Ther. 2022 Apr;28(4):204.e1-204.e10.  doi: 10.1016/j.jtct.2022.01.020. Epub 2022 Jan 31.