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 |
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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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