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.

• Authors: Filippo Milano, Jonathan A Gutman, H Joachim Deeg, Eneida R Nemecek, Joachim Baumgart, Laurel Thur, Ann Dahlberg, Rachel B Salit, Corinne Summers, Frederick R Appelbaum, Colleen Delaney
• Journal: Blood advances (Blood Adv) Vol. 4 Issue 14 Pg. 3302-3310 (07 28 2020) ISSN: 2473-9537 [Electronic] United States
• PMID: 32706891 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by The American Society of Hematology.

Chemical References

• treosulfan
• Busulfan

Topics

• Busulfan (analogs & derivatives, therapeutic use)
• Fetal Blood
• Graft vs Host Disease (prevention & control)
• Humans
• Middle Aged
• Prospective Studies