{"doi":"10.1002/ajh.27251","title":"Long‐term outcomes after unrelated donor transplantation for severe sickle cell disease on the BMT CTN 0601 trial","abstract":"HLA-matched sibling donor transplantation accounts for the majority of transplants performed for sickle cell disease (SCD). However, only about 18% of patients in the United States with SCD will have unaffected human leukocyte antigen (HLA)-matched siblings or one with sickle trait, limiting applicability. A Blood and Marrow Transplant Clinical Trials Network phase II trial of HLA-matched unrelated donor bone marrow transplantation (URD BMT) for severe SCD was conducted between 2008 and 2014 and enrolled patients aged 3–19 years (BMT CTN 0601, NCT00745420).1 A reduced intensity immunosuppressive conditioning regimen (RIC) of alemtuzumab (45 mg; days −22 to −19), fludarabine (150 mg/m2; day −8 to −4), and melphalan (140 mg/m2; day −3) was employed using alemtuzumab early to provide recipient immune suppression to overcome a higher risk of graft rejection (GR) with URD BMT in SCD patients while also limiting toxicities associated with myeloablative agents.1 The trial met a pre-specified primary endpoint of 75% 1-year event-free survival (EFS). However, as previously reported, the incidence of 1-year acute and extensive chronic graft-versus-host disease (GVHD) were unacceptably high at 17% and 38%, respectively. This report details long-term outcomes in this previously reported cohort as an important consideration for therapeutic trials as follow-up is usually limited to early time points. Follow-up information beyond 2 years post-BMT was available for 20 of 21 survivors described in the initial report through the Center for International Blood and Marrow Transplant Research (CIBMTR) database, which collects patient-level data from transplant centers annually for 5 years and then every 2 years for as long the center maintains contact with the patient (www.cibmtr.org). Median follow-up was 97 months (range 11–144). Six patients were lost to follow-up at 11 months, 4.0, 4.5, 5.5, 5.5, and 6 years after transplantation. For this report, GR, GVHD, EFS, and overall survival (OS) were examined similar to the initial report.1 The incidence of GR and chronic GVHD was calculated using the cumulative incidence estimator to accommodate competing risks. Probabilities of EFS and OS were calculated using the Kaplan–Meier estimator. Surviving patients were censored at the last follow-up or death. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). The median age of this cohort at transplant was 13 years (range: 6–18); 5 were 6–9 years old, 10 were 10–15 years old, and 6 were 16–19 years old (Table S1). Median donor age was 34 years (range: 21–53). Indications included stroke (N = 11), vaso-occlusive episodes (N = 5), acute chest syndrome (N = 3), and high transcranial Doppler velocity (>200 cm/s) (N = 2). The median age of recipients at the current time is 21 years (range: 11–25). Eighteen (86%) had ≥5 years of follow-up. Three patients died beyond 2 years post-transplant. Two deaths were secondary to complications of chronic GVHD at 2.6 and 3.9 years. A third patient who had primary GR (reported in the initial report), underwent a second myeloablative URD umbilical cord blood transplant 27 months after the first and died at 2.5 years after the first transplant of grade IV acute GVHD that developed following the second transplant. Consequently, the 5- and 8-year probabilities of OS were 68% (95% CI: 48%–82%) (Figure 1A). With a single secondary GR 5 years after transplantation, the 5- and 8-year probabilities of EFS were 61% (95% CI: 41%–76%) and 57% (95% CI: 37%–73%), respectively (Figure 1B). The 8-year GR rate is 14%, similar to that previously reported after myeloablative or reduced intensity alternative donor transplantation.2 At last follow-up, performance scores for 19 of 20 patients were reported as 90–100 (n = 13) and 70–80 (n = 6). There were no central nervous system (CNS), pulmonary, or vaso-occlusive events reported after successful donor engraftment. No patient reported pulmonary, cardiac, hepatic, renal, or C","journal":"American Journal of Hematology","year":2024,"id":444169,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":443055,"name":"Jianqun Kou","orcid":null,"position":1,"is_corresponding":false},{"id":1259713,"name":"Martin Andreánsky","orcid":null,"position":2,"is_corresponding":false},{"id":893063,"name":"Monica Bhatia","orcid":"0000-0003-2500-0958","position":3,"is_corresponding":false},{"id":1259311,"name":"Joel A. Brochstein","orcid":"0000-0001-6148-4190","position":4,"is_corresponding":false},{"id":263438,"name":"Sonali Chaudhury","orcid":"0000-0001-9816-5126","position":5,"is_corresponding":false},{"id":917750,"name":"Ann E. Haight","orcid":"0000-0001-8158-0091","position":6,"is_corresponding":false},{"id":1117364,"name":"Hilary Haines","orcid":"0009-0002-7516-1178","position":7,"is_corresponding":false},{"id":312102,"name":"David A. Jacobsohn","orcid":"0000-0001-6119-3270","position":8,"is_corresponding":false},{"id":862772,"name":"Jennifer Jaroscak","orcid":null,"position":9,"is_corresponding":false},{"id":312105,"name":"Kimberly A. Kasow","orcid":"0000-0002-0651-8666","position":10,"is_corresponding":false},{"id":380283,"name":"Lakshmanan Krishnamurti","orcid":"0000-0003-3242-0037","position":11,"is_corresponding":false},{"id":331475,"name":"John E. Levine","orcid":"0000-0002-5611-7828","position":12,"is_corresponding":false},{"id":1105984,"name":"Kathryn Leung","orcid":"0000-0002-7124-3136","position":13,"is_corresponding":false},{"id":105520,"name":"David M. Margolis","orcid":"0000-0001-5714-0002","position":14,"is_corresponding":false},{"id":324738,"name":"Lolie C. Yu","orcid":null,"position":15,"is_corresponding":false},{"id":122977,"name":"Mary M. Horowitz","orcid":"0000-0002-9502-785X","position":16,"is_corresponding":false},{"id":483176,"name":"Naynesh Kamani","orcid":"0000-0003-1582-8874","position":17,"is_corresponding":false},{"id":632130,"name":"Mark C. Walters","orcid":"0000-0002-6515-4559","position":18,"is_corresponding":false},{"id":263447,"name":"Shalini Shenoy","orcid":"0000-0002-9283-607X","position":19,"is_corresponding":false},{"id":122964,"name":"Mary Eapen","orcid":"0000-0001-6193-4243","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-19T02:01:33.526738Z","pmid":"38343182","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":[]}