Faculty Collaboration Database

Treosulfan-based conditioning and hematopoietic cell transplantation for nonmalignant diseases: a prospective multicenter trial. Biol Blood Marrow Transplant 2014 Dec;20(12):1996-2003

Date

09/10/2014

Pubmed ID

25196857

Pubmed Central ID

PMC4324724

DOI

10.1016/j.bbmt.2014.08.020

Scopus ID

2-s2.0-84912123151 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

Hematopoietic cell transplantation is an effective treatment for patients with nonmalignant diseases and for many is the only known cure. Conventional myeloablative regimens have been associated with unacceptably high early transplant-related mortality (TRM), particularly in patients with comorbid conditions. This prospective multicenter trial was designed to determine the safety and engraftment efficacy of treosulfan-based conditioning in patients with nonmalignant diseases. Thirty-one patients received HLA-matched related (n = 4) or unrelated (n = 27) grafts after conditioning with treosulfan (total dose, 42 g/m(2)), fludarabine (total dose, 150 mg/m(2)), ± thymoglobulin (6 mg/kg; n = 22). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. All patients engrafted. Day-100 TRM was 0%. With a median follow-up of 2 years, the 2-year survival was 90%. Three patients died of GVHD, recurrent hemophagocytic lymphohistiocytosis, and a surgical complication, respectively. The cumulative incidences of grades II to IV and III to IV acute GVHD at day 100 and chronic GVHD at 2 years were 62%, 10%, and 21%, respectively. Patients who received thymoglobulin had a significantly lower incidence of grades III to IV acute GVHD (0% versus 33%; P = .005). These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with low toxicity and improved survival in patients with nonmalignant diseases and support the need for future disease-specific clinical trials.

Author List

Burroughs LM, Nemecek ER, Torgerson TR, Storer BE, Talano JA, Domm J, Giller RH, Shimamura A, Delaney C, Skoda-Smith S, Thakar MS, Baker KS, Rawlings DJ, Englund JA, Flowers ME, Deeg HJ, Storb R, Woolfrey AE

Author

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
Adult
Anemia, Aplastic
Antilymphocyte Serum
Antineoplastic Agents, Alkylating
Busulfan
Child
Child, Preschool
Fanconi Anemia
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Infant
Male
Methotrexate
Myeloablative Agonists
Prospective Studies
Tacrolimus
Transplantation Conditioning
Unrelated Donors
Vidarabine