Faculty Collaboration Database

Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation: Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium. Biol Blood Marrow Transplant 2018 Aug;24(8):1651-1656

Date

05/13/2018

Pubmed ID

29753157

Pubmed Central ID

PMC6108922

DOI

10.1016/j.bbmt.2018.04.025

Scopus ID

2-s2.0-85047460893 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m²/day (BSA ≤ .5 m²), 12 g/m²/day (BSA > .5 to 1.0 m²), or 14 g/m²/day (BSA > 1.0 m²) on days -6 to -4; fludarabine 30 mg/m²/day on days -6 to -2; and a single fraction of 200 cGy total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.

Author List

Nemecek ER, Hilger RA, Adams A, Shaw BE, Kiefer D, Le-Rademacher J, Levine JE, Yanik G, Leung W, Talano JA, Haut P, Delgado D, Kapoor N, Petrovic A, Adams R, Hanna R, Rangarajan H, Dalal J, Chewning J, Verneris MR, Epstein S, Burroughs L, Perez-Albuerne ED, Pulsipher MA, Delaney C

Authors

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Busulfan
Child
Child, Preschool
Female
Graft Survival
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Infant
Leukemia, Myeloid, Acute
Male
Myelodysplastic Syndromes
Survival Analysis
Transplantation, Homologous
Vidarabine
Whole-Body Irradiation
Young Adult