Improved Outcomes after Allogenic Hematopoietic Stem Cell Transplantation with Fludarabine/Treosulfan for Patients with Myelodysplastic Syndromes

Abstract

While allogeneic hematopoietic stem cell transplantation (allo-HCT) currently offers the only curative option for patients with myelodysplastic syndrome (MDS), there is still a high risk of relapse or transplant-related complications. We collected data on all patients who had undergone allo-HCT at our center (Copenhagen University Hospital) between 2000 and 2018. In total, 215 patients with MDS (n = 196) or chronic myelomonocytic leukemia (n = 19) were included. Estimated 1-year overall survival (OS) was 70.3% (95% confidence interval [CI], 64.2% to 77.0%), and the median survival was 7.7 years (95% CI, 4.7 to indeterminable). There was a significant improvement in OS over time (P = .011, comparing 2000 to 2010, 2010 to 2014, and 2014 to 2018). Treatment was standardized throughout the study period, allowing comparison between patients receiving nonmyeloablative (NMA, n = 124), standard myeloablative (SMA, n = 36), and fludarabine and treosulfan (FluTreo, n = 55) conditioning. Flu-Treo has myeloablative properties but lower toxicity and replaced standard myeloablative conditioning at our center in 2014. The FluTreo group was significantly older and had more comorbidities than the SMA group but similar disease severity. One-year OS was 84.0% (95% CI, 74.3% to 94.9%), 58.3% (95% CI, 44.3% to 76.9%), and 68.3% (95% CI, 60.2% to 77.5%) for FluTreo, SMA, and NMA, respectively (P = .04). In univariate analysis, Revised International Scoring System (IPSS-R) (high versus low), donor sex mismatch, and cytomegalovirus status mismatch were significant factors for OS. In multivariate analysis of OS including age, IPSS-R, and HCT specific comorbidity index, NMA was borderline inferior to FluTreo (P = .073) while SMA was significantly inferior to FluTreo with a hazard ratio of 6.89 (95% CI, 2.53 to 18.77, P < .001). The introduction of FluTreo allowed us to administer a myeloablative regimen to a broader patient group and shows promising results.

Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced‐intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT

“…This confirms prior small studies of treosulfan in MDS, which showed favourable outcomes and suggest that treosulfan may have a specific role in MDS. [27][28][29] The tolerability and efficacy of treosulfan in older and less fit patients allows allo-HCT in the older MDS population, often with comorbidities.…”

“…The five-year non-relapse mortality (NRM) rates in the entire group was 30% (95% CI, [28][29][30][31][32][33]. The NRM rate was 30% (95% CI, [25][26][27][28][29][30][31][32][33][34][35], 27% (95% CI, 23-30) and 34% (95% CI, 31-38) after FT, RIC and MAC, respectively (P = 0Á008, Figure 1). Table II outlines the univariate analysis of predicting factors for NRM.…”

“…The five-year cumulative incidence of relapse in the entire group was 30% (95% CI, [27][28][29][30][31][32]. The relapse rate was 25% (95% CI, 21-30), 38% (95% CI, 34-42) and 25% (95% CI, 22-29) after FT, RIC and MAC, respectively (P > 0Á001, Figure 2).…”

“…These studies showed that this combination can be considered as a reduced‐toxicity regimen with a limited rate of acute GVHD and NRM and an intense anti‐leukaemia effect. In addition, several relatively small studies explored the use of FT in MDS patients with a promising outcome 27–29 . In this study, we used the database of the Chronic Malignancies Working Party (CMWP) of the EBMT to retrospectively compare the outcomes following FT, in a large MDS patient cohort with those following other RIC and MAC regimens.…”

“…In addition, several relatively small studies explored the use of FT in MDS patients with a promising outcome. [27][28][29] In this study, we used the database of the Chronic Malignancies Working Party (CMWP) of the EBMT to retrospectively compare the outcomes following FT, in a large MDS patient cohort with those following other RIC and MAC regimens.…”