{"doi":"10.1056/nejmoa2027372","title":"Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease","abstract":"BACKGROUND: Dipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known. METHODS: We conducted a two-stage, phase 2 clinical trial to test whether sitagliptin plus tacrolimus and sirolimus would reduce the incidence of grade II to IV acute GVHD from 30% to no more than 15% by day 100. Patients received myeloablative conditioning followed by mobilized peripheral-blood stem-cell transplants. Sitagliptin was given orally at a dose of 600 mg every 12 hours starting the day before transplantation until day 14 after transplantation. RESULTS: A total of 36 patients who could be evaluated, with a median age of 46 years (range, 20 to 59), received transplants from matched related or unrelated donors. Acute GVHD occurred in 2 of 36 patients by day 100; the incidence of grade II to IV GVHD was 5% (95% confidence interval [CI], 1 to 16), and the incidence of grade III or IV GVHD was 3% (95% CI, 0 to 12). Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% (95% CI, 13 to 41) and 37% (95% CI, 22 to 53), respectively. GVHD-free, relapse-free survival was 46% (95% CI, 29 to 62) at 1 year. Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation. CONCLUSIONS: In this nonrandomized trial, sitagliptin in combination with tacrolimus and sirolimus resulted in a low incidence of grade II to IV acute GVHD by day 100 after myeloablative allogeneic hematopoietic stem-cell transplantation. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02683525.).","journal":"New England Journal of Medicine","year":2021,"id":154771,"datarank":2.5007827727014327,"base_score":4.127134385045092,"endowment":4.127134385045092,"self_citation_contribution":0.6190701577567639,"citation_network_contribution":1.881712614944669,"self_endowment_contribution":0.6190701577567639,"citer_contribution":1.881712614944669,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":58,"citers_with_citation_signal":43,"citers_with_endowment":43,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02683525"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":361383,"name":"Mohammad Abu Zaid","orcid":"0000-0002-4018-6941","position":1,"is_corresponding":false},{"id":655510,"name":"Jennifer E. Schwartz","orcid":"0009-0005-0070-095X","position":2,"is_corresponding":false},{"id":656223,"name":"Teresa C. Thakrar","orcid":null,"position":3,"is_corresponding":false},{"id":656224,"name":"Ann J. Blakley","orcid":null,"position":4,"is_corresponding":false},{"id":655511,"name":"Rafat Abonour","orcid":"0000-0003-1491-2548","position":5,"is_corresponding":false},{"id":226973,"name":"Michael J. Robertson","orcid":"0000-0003-2610-680X","position":6,"is_corresponding":false},{"id":326018,"name":"Hal E. Broxmeyer","orcid":"0000-0001-6575-0476","position":7,"is_corresponding":false},{"id":655512,"name":"Shuhong Zhang","orcid":"0000-0002-3147-110X","position":8,"is_corresponding":false},{"id":12595,"name":"Sherif S. Farag","orcid":"0000-0002-3088-843X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:43:54.469024Z","pmid":"33406328","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}