{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:51:19Z","timestamp":1791366679021,"version":"4.3.1"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe sickle cell disease (SCD) leads to recurrent vaso\u2010occlusive events (VOEs), progressive organ damage, and premature death. Autologous gene therapy has emerged as a potential curative strategy, but trial efficacy must be interpreted together with mobilization, apheresis collection, manufacturing, conditioning, cost, fertility preservation, and long\u2010term surveillance requirements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy, safety, and treatment\u2010delivery feasibility of autologous gene therapy for SCD across lentiviral, shmiR\u2010BCL11A, CRISPR\u2010Cas9, CRISPR\u2010Cas12a, and base\u2010editing platforms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, FDA, and EMA sources, and ASH\/EHA\/EBMT\/ASPHO conference proceedings through June 23, 2026. Eligible studies were interventional trials or long\u2010term follow\u2010up studies of autologous gene therapy for SCD. Two reviewers independently screened records, extracted data, and assessed risk of bias. Because endpoint definitions were heterogeneous and fewer than three prospectively comparable cohorts were available for the main efficacy outcomes, formal pooling and forest plots were not performed; outcome proportions are presented descriptively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The updated synthesis included 25 reports describing nine interventional clinical programs and associated follow\u2010up reports, with 148 infused patients across lentiviral, shmiR, CRISPR\u2010Cas9, CRISPR\u2010Cas12a, and base\u2010editing platforms. Prospectively defined VF12 was 96.7% (29\/30) in the exa\u2010cel pivotal cohort, and severe VOE resolution was 100% (25\/25) in the lovo\u2010cel pivotal cohort; both products achieved transfusion independence in evaluable patients. Reni\u2010cel and risto\u2010cel added contemporary Cas12a and base\u2010editing evidence, with early follow\u2010up showing high HbF induction and few or no reported post\u2010infusion VOEs, but follow\u2010up was shorter, and endpoints were not pooled with pivotal VF12 cohorts. Treatment\u2010delivery outcomes differed across programs, including 44\/46 infused for exa\u2010cel and 35\/47 infused for lovo\u2010cel.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Autologous gene therapy for SCD produces substantial short\u2010 to medium\u2010term reductions in severe VOEs and improves hemoglobin biology, but certainty remains limited by single\u2010arm designs, small samples, evolving protocols, and incomplete long\u2010term follow\u2010up. Successful delivery depends on separable processes: transfusion preparation, mobilization, apheresis collection, ex\u00a0vivo manufacturing\/editing, product release, conditioning, and reinfusion. Long\u2010term safety, fertility, organ outcomes, reimbursement, and global scalability remain unresolved implementation barriers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.70260","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T05:52:32Z","timestamp":1783144352000},"page":"1168-1180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy, Safety, and Treatment\u2010Delivery Feasibility of Autologous Gene Therapy for Sickle Cell Disease: A Systematic Review With Descriptive Synthesis of Clinical Trials"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9438-6589","authenticated-orcid":false,"given":"Mahboob Younus","family":"Shaik","sequence":"first","affiliation":[{"name":"Internal Medicine Residency Program CHI St. Vincent Hospital  Hot Springs Arkansas 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