{"doi":"10.1002/ajh.26985","title":"Cardiac effects 2 years after successful non‐myeloablative human leukocyte antigen‐matched related donor hematopoietic cell transplants in sickle cell disease","abstract":"Cardiopulmonary disease, particularly elevated tricuspid regurgitation velocity (TRV ≥2.5 m/s), remains a significant risk marker for early mortality in individuals with sickle cell disease (SCD). Indeed, diastolic dysfunction and elevated TRV are independent risk factors for mortality.1 Hematopoietic cell transplant (HCT) remains the only available curative therapy for SCD. The degree of organ impairment and co-morbidities in many adults with SCD preclude the use of myeloablative regimens due to the risk of chemotherapy-induced organ toxicity. However, our non-myeloablative (NMA) approach has demonstrated success in adults with SCD, including those with end-organ damage.2 We have previously shown that successful NMA allogeneic HCT improves cardiac size, markers of diastolic dysfunction, TRV, and N-terminal pro-B-type natriuretic peptide within the first year post-HCT.3 In this study, we focused on human leukocyte antigen (HLA)-matched related donors (MRD) and broadened our analyses to three centers with a predominantly adult cohort of patients with SCD, extending our follow-up period to 2 years. These three centers used the same NMA regimen with comparable outcomes.2 Patients with SCD underwent NMA MRD HCT at the National Institutes of Health (NIH, NCT00061568 or NCT02105766), University of Illinois, Chicago (UIC NCT01499888), and King Abdulaziz Medical City in Riyadh, Saudi Arabia (KAMCR, RC20/646/R). Routine laboratory parameters, as well as a transthoracic echocardiogram (TTE), were performed before HCT, and at 1 and 2 years post-HCT. Patients with a successful transplant who were free of dialysis or chronic transfusion therapy were included, and both a pre-HCT TTE and a TTE at least 1 year following HCT were required. All patients received alemtuzumab, 300 cGy total body irradiation, and sirolimus; some also received pentostatin and cyclophosphamide preconditioning. Transthoracic echocardiograms were performed using commercially available systems. Cardiac measurements were performed according to the American Society of Echocardiography guidelines1 A generalized estimating equation regression model approach was used to evaluate TTE and laboratory changes from baseline, adjusting for age, gender, and site. Given the number of outcomes tested, a more stringent p-value threshold of .005 was used for significance. Baseline assessments of differences between sites were conducted using Kruskal–Wallis tests for continuous outcomes and Fisher exact tests for categorical variables. The study population consisted of 123 patients (68 NIH, 19 UIC, 36 KAMCR) who had stable engraftment. The mean ± SD age of patients was 29 ± 10 years, and 49 (40%) were female. Eighty-seven percent of patients at the NIH and UIC had hemoglobin SS, while one-third of KAMCR patients had compound heterozygous hemoglobin S beta0 thalassemia. Patients at the NIH and UIC were also older (mean values of 31.0 years at NIH, 33.8 at UIC, 26.1 at KAMCR p = .02) and had a larger body surface area (BSA mean values of 1.8 m2 at NIH, 1.8 at UIC, 1.6 at KAMCR, p < .0001). The TRV was elevated at ≥2.5 m/s in 40% of patients at baseline and was higher in patients at the US sites (mean values of 3.5 m/s at NIH, 4.0 at UIC, 3.0 at KAMCR, p = .004), reflective of more severe disease. Hemoglobin improved significantly in the first year after HCT and continued to improve at 2 years (Table 1). Laboratory results showed improvements in lactate dehydrogenase, total bilirubin, and absolute reticulocyte count within the first year after HCT (Table 1). The left ventricular size, as measured by the left ventricular end-diastolic volume index/BSA (LVEDV/BSA), decreased at 1 year after successful HCT (baseline 76.6 mL/m2 ± 21.9, 1 year 65.9 mL/m2 ± 15.7, p < .0001) and remained stable at 2 years (60.7 mL/m2 ± 15.1, p = .03). Almost all patients have normal right ventricular function at baseline, 1 year, and 2 years post-HCT. Although there is a statistically significant reduction in th","journal":"American Journal of Hematology","year":2023,"id":372880,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1125191,"name":"Emily Limerick","orcid":"0000-0003-1591-2451","position":1,"is_corresponding":false},{"id":750380,"name":"My‐Le Nguyen","orcid":null,"position":2,"is_corresponding":false},{"id":374366,"name":"Wen Li","orcid":"0000-0002-1747-9594","position":3,"is_corresponding":false},{"id":448081,"name":"Neal Jeffries","orcid":null,"position":4,"is_corresponding":false},{"id":1133472,"name":"Shalini S. Ramachandra","orcid":"0000-0002-8402-184X","position":5,"is_corresponding":false},{"id":1133473,"name":"David Tofovic","orcid":"0000-0003-3855-6891","position":6,"is_corresponding":false},{"id":632129,"name":"Damiano Rondelli","orcid":"0000-0001-5243-401X","position":7,"is_corresponding":false},{"id":1133796,"name":"Mohsen Al Zahrani","orcid":null,"position":8,"is_corresponding":false},{"id":1133797,"name":"Ahmed Aljizeeri","orcid":null,"position":9,"is_corresponding":false},{"id":292968,"name":"Santosh L. Saraf","orcid":"0000-0002-8584-4194","position":10,"is_corresponding":false},{"id":314731,"name":"Matthew M. Hsieh","orcid":"0000-0002-3706-6615","position":11,"is_corresponding":false},{"id":314732,"name":"Courtney D. Fitzhugh","orcid":"0000-0002-5306-7167","position":12,"is_corresponding":false},{"id":280938,"name":"Vandana Sachdev","orcid":"0000-0002-1168-5055","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T01:15:58.101083Z","pmid":"37282828","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":[]}