Refined graft-versus-host disease/relapse-free survival in transplant from HLA-identical related or unrelated donors in acute myeloid leukemia

Abstract

Refined graft-versus-host disease (GVHD)/relapse-free survival (GRFS) considers main outcomes of allogeneic stem cell transplant (HSCT), estimating long-term survival without significant morbidity as a surrogate of HSCT success. We compared GRFS in 5059 adults with acute myeloid leukemia (AML), undergoing HSCT in first complete remission from 2000 to 2015 either from a matched sibling (MSD, n = 3731) or unrelated donor (MUD, n = 1328). Median age was 49 (range: 18-76) years. Median follow-up was 32 and 60 months in MSD and MUD, respectively (p < 0.01). Compared to MSD, at 4 years, MUD recipients had lower GRFS, with higher NRM, grade III-IV acute GVHD, and extensive chronic GVHD (HR: 1.42, p < 0.01). We also performed a risk factor analyses, showing unfavorable cytogenetics (HR: 1.42, p < 0.01) and peripheral blood as stem cell source (HR: 1.22, p < 0.01) associated to lower GRFS, while this was higher with in vivo T-cell depletion (TCD, HR: 0.73, p < 0.01) and shorter time from diagnosis to HSCT (HR 0.96, p < 0.01). Different factors, modifiable or not, such as donor type, stem cell source, disease biology, and in vivo TCD, impact on GRFS and this may guide in the future transplant choices to improve morbidity and long-term quality of life.

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

“…Death without engraftment was considered as a competing risk for engraftment and acute GVHD. We defined GVHD relapse-free survival as the absence of grades III to IV acute GVHD, severe chronic GVHD, disease relapse, or death from any cause after HSCT [10].…”

Assessment of Individual versus Composite Endpoints of Acute Graft-versus-Host Disease in Determining Long-Term Survival after Allogeneic Transplantation

“…cGVHD requiring any IST has been incorporated into composite endpoints, in recognition of the risk of morbidity and mortality following HCT [6,9,10,12,13,15,16,[22][23][24][25][26][27]. In our cohort, we identified cGVHD requiring IST as an independent risk factor for death (HR, 1.69; 95% CI, 1.16 to 2.46) ( Table 3).…”

“…Since the initial report by Holtan et al [6], more data are emerging from retrospective single-and multi-center studies [6,9,10,12,13,15,16,[22][23][24][25][26][27] investigating the impact of GRFS on the relative success or failure after allogeneic HCT [5]. The findings raise important questions regarding the use of GRFS in clinical trials given how various definitions and historical (or published) incidences of events in the population affect the findings.…”

“…This analysis was based on previous single-center and registry analyses in large adult and pediatric HCT cohorts receiving GVHD prophylaxis with tacrolimus and methotrexate that estimated a 1-year GRFS in the range of 23% to 31%, suggesting that a composite endpoint identifies a large fraction of HCT survivors with suboptimal outcomes [6]. Subsequent studies have identified various patient and donor graft characteristics (eg, unrelated donor, peripheral blood stem cell [PBSC] graft) that are major determinants of GRFS [6,[9][10][11][12], More recent studies have focused on refining the definitions of GRFS, particularly as related to the cGVHD component [13][14][15][16]. However, to our knowledge, no previous study has assessed the long-term survival implications of attaining the GRFS state when compared to traditional GVHD endpoints; and importantly, the degree to which altering GRFS, as hypothesized in HCT clinical trials, can modify a patient's subsequent risk of death.…”

23rd Nantes Actualités Transplantation: “Genomics and Immunogenetics of Kidney and Inflammatory Diseases—Lessons for Transplantation”

“…As Patrice Chevallier (Centre Hospitalier Universitaire de Nantes, France) reminded us, transplantation success is highly dependent on the HLA matching level between D/R with a growing importance of permissive versus nonpermissive mismatches. 7,8 Jean-Luc Taupin (Hôpital St-Louis, Paris, France) highlighted the strong negative association between donor-specific anti-HLA antibodies, especially for the complement-driven mechanisms, 9 and kidney allograft survival. 10 A better understanding of HLA evolution history and allele complexity through immunogenetics is, therefore, of prime importance for improving matching and transplantation outcomes.…”