Metformin for treatment of cytopenias in children and young adults with Fanconi anemia Journal Article
| Authors: | Pollard, J. A.; Furutani, E.; Liu, S.; Esrick, E.; Cohen, L. E.; Bledsoe, J.; Liu, C. W.; Lu, K.; de Haro, M. J. R.; Surrallés, J.; Malsch, M.; Kuniholm, A.; Galvin, A.; Armant, M.; Kim, A. S.; Ballotti, K.; Moreau, L.; Zhou, Y.; Babushok, D.; Boulad, F.; Carroll, C.; Hartung, H.; Hont, A.; Nakano, T.; Olson, T.; Sze, S. G.; Thompson, A. A.; Wlodarski, M. W.; Gu, X.; Libermann, T. A.; D'Andrea, A.; Grompe, M.; Weller, E.; Shimamura, A. |
| Article Title: | Metformin for treatment of cytopenias in children and young adults with Fanconi anemia |
| Abstract: | 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/mL; or an absolute neutrophil count, 1000 cells/mL) 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. © 2022 by The American Society of Hematology. |
| Keywords: | adolescent; adult; child; clinical article; school child; human cell; clinical trial; drug tolerability; fatigue; diarrhea; dose response; drug safety; side effect; treatment duration; anorexia; thrombocyte; gastrointestinal symptom; nausea; vomiting; hemoglobin; hemoglobin blood level; proteomics; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; pruritus; rash; confidence interval; alanine aminotransferase; aspartate aminotransferase; hyperkalemia; correlation analysis; feasibility study; neutrophil; drug mechanism; pilot study; blood analysis; open study; erythrocyte; antiinflammatory activity; anxiety; headache; optimal drug dose; eye disease; blood cell count; maximum tolerated dose; drug dose increase; dyspepsia; metformin; cytopenia; platelet count; fanconi anemia; epiphora; eye edema; eye redness; human; male; female; article; absolute neutrophil count; treatment response time |
| Journal Title: | Blood Advances |
| Volume: | 6 |
| Issue: | 12 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2022-06-28 |
| Start Page: | 3803 |
| End Page: | 3811 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2021006490 |
| PUBMED: | 35500223 |
| PROVIDER: | scopus |
| PMCID: | PMC9631552 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
