The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children’s Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial

Autor: Julie M. Gastier-Foster, Michael J. Borowitz, James G. Douglas, Elizabeth A. Raetz, Kirk R. Schultz, William L. Carroll, Donna A. Wall, Y. Barnes, Denise L. Howrie, Michael A. Pulsipher, Candace Taylor, Sharon Gardner, Bryan Langholz, David T. Teachey, Stephan A. Grupp, Rakesh K. Goyal, Nancy Bunin
Rok vydání: 2014
Předmět:
Male
medicine.medical_specialty
Transplantation Conditioning
Thrombotic microangiopathy
Adolescent
Clinical Trials and Observations
medicine.medical_treatment
Immunology
Graft vs Host Disease
chemical and pharmacologic phenomena
Hematopoietic stem cell transplantation
Biochemistry
Gastroenterology
Tacrolimus
law.invention
Young Adult
Randomized controlled trial
immune system diseases
law
hemic and lymphatic diseases
Internal medicine
Humans
Transplantation
Homologous
Medicine
cardiovascular diseases
Child
Sirolimus
business.industry
Hematopoietic Stem Cell Transplantation
Infant
Cell Biology
Hematology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
equipment and supplies
medicine.disease
Minimal residual disease
Surgery
Transplantation
Methotrexate
surgical procedures
operative
Child
Preschool
Female
business
Immunosuppressive Agents
Whole-Body Irradiation
medicine.drug
Zdroj: Blood. 123:2017-2025
ISSN: 1528-0020
0006-4971
Popis: Sirolimus has activity against acute lymphoblastic leukemia (ALL) in xenograft models and efficacy in preventing acute graft-versus-host disease (aGVHD). We tested whether addition of sirolimus to GVHD prophylaxis of children with ALL would decrease aGVHD and relapse. Patients were randomized to tacrolimus/methotrexate (standard) or tacrolimus/methotrexate/sirolimus (experimental). The study met futility rules for survival after enrolling 146 of 259 patients. Rate of Grade 2-4 aGVHD was 31% vs 18% (standard vs experimental, P = .04), however, grade 3-4 aGVHD was not different (13% vs 10%, P = .28). Rates of veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA) were lower in the nonsirolimus arm (9% vs 21% VOD, P = .05; 1% vs 10% TMA, P = .06). At 2 years, event free survival (EFS) and overall survival (OS) were 56% vs 46%, and 65% vs 55% (standard vs experimental), respectively (P = .28 and .23). Multivariate analysis showed increased relapse risk in children with ≥0.1% minimal residual disease (MRD) pretransplant, and decreased risk in patients with grades 1-3 aGVHD (P = .04). Grades 1-3 aGVHD were associated with improved EFS (P = .02), whereas grade 4 aGVHD and extramedullary disease at diagnosis led to inferior OS. Although addition of sirolimus decreased aGVHD, survival was not improved. This study is registered with ClinicalTrials.gov as #NCT00382109.
Databáze: OpenAIRE
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