Graft-versus-Host Disease–Free, Relapse-Free Survival after Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome

Abstract

Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult patients (N = 324) who received HSCT with fludarabine and busulfan-based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast > 3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose [<7.5 mg/kg] antithymocyte globulin [ATG]) were independent factors for poor GRFS. Based on these 5 factors, 3 groups (3-year GRFS: 64.9% in low risk, 33.6% in intermediate risk, and 6.6% in high risk; P < .001) were identified. Fixed factor-adjusted GRFS in patients receiving reduced-intensity conditioning (RIC) plus high-dose ATG (≥7.5 mg/kg) was superior (P < .001) to those receiving MAC and/or low-dose ATG. Favorable influences of RIC plus ATG ≥ 7.5mg/kg were evident in the low-risk group defined by fixed factors (3-year GRFS, 38.9% versus 4.4%; P < .001) but were not evident in the high-risk group (3-year GRFS, .0% versus 5.3%; P = .678). Conclusively, this study suggests that risk-adapted selection of conditioning intensity and ATG could improve qualified HSCT outcomes.

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.…”

Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

“…Nowadays, more and more novel strategies were being successfully used as subsequent maintenance therapy after allo-HSCT, which significantly reduced the recurrence of allo-HSCT recipients receiving RIC regimens [37][38][39]. Additionally, the long-term GVHD/ relapse-free survival was also comparable in two arms for AML patients [40][41][42] but superior in RIC arm for MDS patients [43].…”

Role of pretransplant anti‐thymocyte globulin in matched sibling donor stem cell transplantation after reduced intensity conditioning for myelodysplastic syndrome

“…18 In a recent study, we showed that a higher dose of ATG (≥7.5 mg/kg) was associated with better GRFS in patients with MDS receiving peripheral blood stem cell transplantation after a MAC or RIC regimen. 19 The recent use of peripheral blood as a graft source may mitigate the risk of relapse from potentially impaired anti-leukemia effect conferred by ATG. [20][21][22] In order to narrow the uncertainties regarding the role of ATG in MSD-HSCT after RIC, we evaluated only those patients with MDS who received peripheral blood stem cell transplantation from MSD after fludarabine/busulfan (FB)-based RIC regimen in this study.…”