Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study

Abstract

Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.

Conflict of interest statement

Conflict-of-interest disclosure: J.B. is an employee of Medac GmbH, which provided support for this study. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Cumulative incidence to day +100 in CBT recipients. (A) Neutrophil engraftment. (B) Platelet engraftment.

Figure 2.

Survival and other outcomes for CBT recipients. (A) OS (solid red line), RFS (dashed red line), and GRFS (dotted red line) at 3 years after a TREO-based conditioning regimen. Cumulative incidence of overall relapse (B) and TRM (C) at 3 years after a TREO-based conditioning regimen, and of grade II-IV (solid red line) and III-IV (dashed red line) aGVHD to day +100 (D).