Metformin for treatment of cytopenias in children and young adults with Fanconi anemia
Pollard, Jessica A. (Department of Pediatrics, Harvard Medical School, Boston, MA)
Furutani, Elissa (Department of Pediatrics, Harvard Medical School, Boston, MA)
Liu, Shanshan (Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Harvard Medical School, Boston, MA)
Esrick, Erica (Department of Pediatrics, Harvard Medical School, Boston, MA)
Cohen, Laurie E. (Department of Endocrinology, and)
Bledsoe, Jacob (Department of Pathology, Boston Children's Hospital, Boston, MA)
Liu, Chih-Wei (Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC)
Lu, Kun (Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC)
Ramírez de Haro, Ma. José (Institut d'Investigació Biomèdica Sant Pau)
Surrallés i Calonge, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Malsch, Maggie (Clinical Research Operations Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA)
Kuniholm, Ashley (Clinical Research Operations Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA)
Galvin, Ashley (Clinical Research Operations Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA)
Armant, Myriam (Trans Laboratory, Boston Children's Hospital, Boston, MA)
Kim, Annette S. (righam and Women's Hospital (Boston, Estats Units d'Amèrica))
Ballotti, Kaitlyn (Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA)
Moreau, Lisa (Comprehensive Center for Fanconi Anemia, Dana-Farber Cancer Institute, Boston, MA)
Zhou, Yu (Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA)
Babushok, Daria (Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA)
Boulad, Farid (Pediatric Hematology-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY)
Carroll, Clint (Pediatric Hematology-Oncology, The Children's Hospital at TriStar Centennial, Nashville, TN)
Hartung, Helge (Pediatric Hematology-Oncology, Children's Hospital of Philadelphia, Philadelphia, PA)
Hont, Amy (Pediatric Hematology-Oncology, Children's National Medical Center, Washington, DC)
Nakano, Taizo (Pediatric Hematology-Oncology, Children's Hospital Colorado, Denver, CO)
Olson, Tim (Pediatric Hematology-Oncology, Children's Hospital of Philadelphia, Philadelphia, PA)
Sze, Sei-Gyung (Department of Pediatrics, Maine Medical Center, Tufts University School of Medicine, Portland, ME)
Thompson, Alexis A. (Pediatric Hematology-Oncology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL)
Wlodarski, Marcin W. (Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN)
Gu, Xuesong (Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics and Systems Biology Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA)
Libermann, Towia A. (Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics and Systems Biology Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA)
D'Andrea, Alan (Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA)
Grompe, Markus (Oregon Stem Cell Center, Department of Pediatrics, Papé Family Institute, Oregon Health and Science University, Portland, OR; and)
Weller, Edie (Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Harvard Medical School, Boston, MA)
Shimamura, Akiko (Department of Pediatrics, Harvard Medical School, Boston, MA)

Fecha:	2022
Resumen:	Fanconi anemia (FA), a genetic DNA repair disorder characterized by marrow failure and cancer susceptibility. In FA mice, metformin improves blood counts and delays tumor development. We conducted a single institution study of metformin in nondiabetic patients with FA to determine feasibility and tolerability of metformin treatment and to assess for improvement in blood counts. Fourteen of 15 patients with at least 1 cytopenia (hemoglobin < 10 g/dL; platelet count < 100 000 cells/µL; or an absolute neutrophil count < 1000 cells/µL) were eligible to receive metformin for 6 months. Median patient age was 9. 4 years (range 6. 0-26. 5). Thirteen of 14 subjects (93%) tolerated maximal dosing for age; 1 subject had dose reduction for grade 2 gastrointestinal symptoms. No subjects developed hypoglycemia or metabolic acidosis. No subjects had dose interruptions caused by toxicity, and no grade 3 or higher adverse events attributed to metformin were observed. Hematologic response based on modified Myelodysplastic Syndrome International Working Group criteria was observed in 4 of 13 evaluable patients (30. 8%; 90% confidence interval, 11. 3-57. 3). Median time to response was 84. 5 days (range 71-128 days). Responses were noted in neutrophils (n = 3), platelets (n = 1), and red blood cells (n = 1). No subjects met criteria for disease progression or relapse during treatment. Correlative studies explored potential mechanisms of metformin activity in FA. Plasma proteomics showed reduction in inflammatory pathways with metformin. Metformin is safe and tolerable in nondiabetic patients with FA and may provide therapeutic benefit. This trial was registered at as #NCT03398824.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Blood advances, Vol. 6 (june 2022) , p. 3803-3811, ISSN 2473-9537

DOI: 10.1182/bloodadvances.2021006490
PMID: 35500223

9 p, 1.0 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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