PMID- 25482865 OWN - NLM STAT- MEDLINE DCOM- 20151026 LR - 20211203 IS - 1523-6536 (Electronic) IS - 1083-8791 (Linking) VI - 21 IP - 3 DP - 2015 Mar TI - Mammalian target of rapamycin inhibitor-associated stomatitis in hematopoietic stem cell transplantation patients receiving sirolimus prophylaxis for graft-versus-host disease. PG - 503-8 LID - S1083-8791(14)01389-5 [pii] LID - 10.1016/j.bbmt.2014.11.680 [doi] AB - The mammalian target of rapamycin (mTOR) inhibitor sirolimus is effective in reducing incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Agents that inhibit the mTOR pathway are known to be associated with significant and potentially dose-limiting toxicities, including stomatitis. The objective of this study was to report the clinical features and management outcomes of sirolimus-associated oral ulcers in the context of post-HSCT prophylaxis of GVHD. Seventeen patients, from a study cohort of 967, who were treated with sirolimus as prophylaxis for GVHD after allogeneic HSCT at the Dana-Farber/Brigham and Women's Cancer Center developed oral ulcers and were referred to the oral medicine clinic for evaluation and treatment over a period of 6 years. Clinical characteristics (appearance, anatomic site, size) and therapeutic outcomes (time to complete resolution) were documented. Median time to onset of oral ulceration was 55 days after allogeneic HSCT (range, 6 to 387 days); 92.9% of ulcers were located on nonkeratinized mucosa, with the ventrolateral tongue the most common site of involvement. Thirteen patients were treated with topical corticosteroid therapy; 12 of these patients also required intralesional corticosteroid injections. Clinical improvement (resolution of the lesions and improvement of symptoms) was noted in all cases, with no reported adverse events. Median time to complete resolution after onset of therapy was 14 days (range, 2 to 70 days). Patients receiving sirolimus for GVHD prophylaxis may develop painful oral ulcerations, which can be effectively managed with topical steroid treatment. Further prospective studies are needed to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of interventions. CI - Copyright (c) 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. FAU - Villa, Alessandro AU - Villa A AD - Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. Electronic address: avilla@partners.org. FAU - Aboalela, Ali AU - Aboalela A AD - Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. FAU - Luskin, Katharine A AU - Luskin KA AD - School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut. FAU - Cutler, Corey S AU - Cutler CS AD - Department of Medical Oncology, Brigham & Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts. FAU - Sonis, Stephen T AU - Sonis ST AD - Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. FAU - Woo, Sook Bin AU - Woo SB AD - Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. FAU - Peterson, Douglas E AU - Peterson DE AD - School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut; Department of Oral Health and Diagnostic Sciences, School of Dental Medicine and Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut. FAU - Treister, Nathaniel S AU - Treister NS AD - Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20141205 PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - 0 (Immunosuppressive Agents) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adult MH - Aged MH - Allografts MH - Female MH - Graft vs Host Disease/pathology/*prevention & control MH - *Hematopoietic Stem Cells MH - Humans MH - Immunosuppressive Agents/administration & dosage/*adverse effects MH - Male MH - Middle Aged MH - Retrospective Studies MH - Sirolimus/administration & dosage/*adverse effects MH - *Stomatitis/chemically induced/epidemiology/pathology/therapy MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors MH - Time Factors OTO - NOTNLM OT - Graft-versus-host-disease OT - Management OT - Sirolimus OT - Ulcers EDAT- 2014/12/09 06:00 MHDA- 2015/10/27 06:00 CRDT- 2014/12/09 06:00 PHST- 2014/09/08 00:00 [received] PHST- 2014/11/24 00:00 [accepted] PHST- 2014/12/09 06:00 [entrez] PHST- 2014/12/09 06:00 [pubmed] PHST- 2015/10/27 06:00 [medline] AID - S1083-8791(14)01389-5 [pii] AID - 10.1016/j.bbmt.2014.11.680 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2015 Mar;21(3):503-8. doi: 10.1016/j.bbmt.2014.11.680. Epub 2014 Dec 5.