Send to

Choose Destination
Biol Blood Marrow Transplant. 2018 Aug;24(8):1651-1656. doi: 10.1016/j.bbmt.2018.04.025. Epub 2018 May 9.

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.

Author information

Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon. Electronic address:
West German Cancer Center, University Hospital Essen, University Duisburg Essen, Essen, Germany.
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Division of Pediatric Hematology/Oncology, Mayo Clinic Rochester, Rochester, Minnesota.
Division of Pediatric Hematology/Oncology, Mount Sinai School of Medicine, New York, New York.
Division of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, Michigan.
Division of Pediatric Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Division of Pediatric Hematology/Oncology, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
Division of Pediatric Hematology/Oncology, Riley Children's Hospital at Indiana University Health, Indianapolis, Indiana.
Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine at University of Southern California, Los Angeles, California.
Division of Pediatric Hematology/Oncology, Johns Hopkins All Children's Hospital, St. Petersburg, Florida.
Division of Pediatric Hematology/Oncology, Mayo Clinic Arizona and Phoenix Children's Hospital, Phoenix, Arizona.
Division of Pediatric Hematology/Oncology, Cleveland Clinic Foundation, Cleveland, Ohio.
Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, Columbus, Ohio.
Division of Pediatric Hematology/Oncology, The Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
Children's of Alabama, University of Alabama at Birmingham, Birmingham, Alabama.
Division of Pediatric Hematology/Oncology, University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota.
Levine Children's Hospital, Carolinas Medical Center, Charlotte, North Carolina.
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington.
Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.


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.


Acute myeloid leukemia; Conditioning regimen; Myelodysplastic syndromes; Stem cell transplantation

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center