Fludarabine–Treosulfan Conditioning Combo Improves Post-Transplant Outcomes in MDS

Standard myeloablative conditioning before allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is significantly inferior to conditioning with fludarabine and treosulfan in patients with myelodysplastic syndrome (MDS), according to study results published in Biology of Blood and Marrow Transplantation (2020 Feb 20. Epub ahead of print).

For this study, Eileen Wedge, MBChB, Department of Hematology, Copenhagen University Hospital, Denmark, and colleagues collected data on all patients who underwent allo-HSCT at Copenhagen University Hospital between 2000 and 2018.

A total of 215 patients with MDS (n = 196) or chronic myelomonocytic leukemia (n = 19) were included in the analysis. The estimated 1-year overall survival (OS) was 70.3% and median survival was 7.7 years. An improvement in OS was noted over time when evaluating the periods between 2000 and 2010, 2010 and 2014, and 2014 and 2018 (P =.011).

Throughout the entire study, treatment was standardized to allow for comparison between patients receiving nonmyeloablative conditioning (n = 124), standard myeloablative conditioning (n = 36), and conditioning with fludarabine and treosulfan (n = 55).

Dr Wedge and colleagues noted that patients in the fludarabine–treosulfan conditioning arm were significantly older and had more comorbidities than those in the standard myeloablative arm, but had similar disease severity.

The 1-year OS was 84% (95% CI, 74.3-94.9%) in the fludarabine–treosulfan arm compared with 58.3% (95% CI, 44.3-76.9%) in the standard myeloablative conditioning arm and 68.3% (95% CI, 60.2-77.5%) in the nonmyeloablative conditioning arm (P = .04).

Univariate analysis showed that the Revised International Prognostic Scoring System classification (IPSS-R), donor sex-mismatch, and cytomegalovirus status mismatch were significant factors for OS.

Multivariate analysis of OS, including age, IPSS-R, and Hematopoietic Cell Transplantation-Comorbidity Index showed that nonmyeloablative conditioning was borderline inferior to conditioning with fludarabine and treosulfan (P = .073).

However, standard myeloablative conditioning was significantly inferior to conditioning with fludarabine and treosulfan (P <.001).

“The introduction of FluTreo [fludarabine–treosulfan] allowed us to administer a myeloablative regimen to a broader patient group and shows promising results,” Dr Wedge et al concluded.—Janelle Bradley