Pre‐transplantation cytoreduction does not benefit advanced myelodysplastic syndrome patients after myeloablative transplantation with grafts from family donors

Abstract

Background The role of pre‐hematopoietic stem cell transplantation (HSCT) cytoreduction with either induction chemotherapy (IC) or hypomethylating agents (HMAs) in treating advanced myelodysplastic syndrome (MDS) remains debatable. We aimed to evaluate pre‐HSCT strategies by comparing the endpoints related to disease control between advanced MDS patients with pre‐HSCT cytoreduction and those with best supportive care. Methods We described 228 consecutive advanced MDS patients who received HSCT from a haploidentical donor (HID, n = 162) or matched related donor (MSD, n = 66) with uniform myeloablative conditioning regimens between January 2015 and December 2018. Of these 228 patients, 131 (57.5%) were treated exclusively with pre‐HSCT best supportive care (BSC), 49 (22.5%) were given HMA, and 48 (21.1%) received both IC and HMA. Propensity score‐matching analysis, multivariate analyses, and subgroup analyses were performed to elucidate the impact of pre‐HSCT strategies on transplant outcomes. Results The 3‐year relapse‐free survival (RFS) rates were 78.2% and 70.0% for the BSC and cytoreduction cohorts (P = 0.189) and were 78.2%, 66.7%, and 73.2% for the BSC, HMA, and HMA+IC groups, respectively (P = 0.269). A propensity score‐matching analysis confirmed that the 3‐year RFS rates were 81.9%, 87.5%, and 66.9% for BSC, cytoreduction complete remission (CR), and cytoreduction non‐CR groups, respectively (P = 0.051). Multivariate analyses demonstrated that pre‐HSCT cytoreduction, older patient age, monosomal karyotype, and interval between diagnosis and HSCT were poor prognostic factors for RFS. In the subgroup analyses, BSC was associated with longer RFS compared to cytoreduction among the younger patients, those with international prognostic scoring system intermediate‐2/high risk at diagnosis, and those with intermediate/poor cytogenetics. Conclusions Different pre‐HSCT therapies did not yield discrepant post‐HSCT outcomes. No benefit in terms of post‐HSCT outcomes were correlated with pre‐HSCT cytoreduction in advanced MDS even for cytoreduction CR patients. Early referral to HSCT is essential for advanced MDS patients.

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

“…For advanced MDS patients, as opposed to patients with AML derived from MDS (MDS-AML) or AML-MRC, early referral for HSCT is essential, as no benefit in terms of post-HSCT outcomes was correlated with pre-HSCT cytoreduction [ 45 ]. In a study of 228 consecutive advanced MDS patients, Sun et al reported that cytoreduction did not improve 3-year DFS (70.0% vs. 78.2%, p = 0.189) compared to supportive care [ 46 ]. In contrast, Wang et al demonstrated that cytoreduction significantly improved the OS rate (62.2% vs. 20.0%, p = 0.013) in MDS-AML patients but not in MDS-EB2 patients (59.2% vs. 62.9%, p = 0.991) [ 47 ].…”