使用一种新型的低毒性移植策略对患有高危输血依赖性地中海贫血的儿童/青少年进行异体移植后的早期移植和免疫动力学:ThalFAbS试验的早期结果

IF 3.6 3区 医学 Q2 HEMATOLOGY Transplantation and Cellular Therapy Pub Date : 2025-03-01 DOI:10.1016/j.jtct.2024.12.016
Enass H Raffa , Taylor M Harris , Chane Choed-Amphai , Melanie Kirby-Allen , Isaac Odame , Muhammad Ali , Joerg Krueger , Karin G Hermans , Soumitra Tole , Jennifer Seelisch , Robert J Klaassen , Lesleigh Abbott , Yogi Raj Chopra , Donna A Wall , Kuang-Yueh Chiang
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引用次数: 0

摘要

背景:输血依赖性地中海贫血患者的同种异体移植是具有挑战性的,一旦有铁超载和慢性输血支持。目的:为这一人群开发了一种移植策略,即降低准备方案的强度和量身定制的免疫抑制,以支持供体移植和预防GVHD。移植前免疫抑制期减少氟达拉滨/泼尼松的剂量,以曲硫胺为基础的制备方案减少环磷酰胺的剂量,引入钙调磷酸酶/无甲氨蝶呤的GVHD预防/植入支持方案与阿巴接受普/西罗莫司/ATG的组合进行了测试。研究设计:ThalFAbS试验是一项前瞻性试点试验(NCT05426252),为12名儿科患者(4名α型地中海贫血,8名β型地中海贫血)设计了一种移植策略,用于治疗输血依赖性地中海贫血的高风险患者。描述性统计用于描述移植结果和免疫恢复。结果:移植后中位随访12个月(范围4-26个月),首批12例患者均及时且持久地进行了三岁供体移植,移植相关发病率和急性GVHD较低,并且在没有输血支持的情况下存活。GVHD仅限于1例2级皮肤急性GVHD患者和3例有限口腔慢性GVHD患者。在低输血支持和低感染率的情况下实现了早期血液学和免疫恢复。中性粒细胞恢复的中位时间为18天(15-24天),血小板恢复的中位时间为18天(12-36天)。无VOD、TA-TMA、败血症。该平台足以支持2例患者的单倍体供体移植。结论:ThalFAbS方法是为满足输血依赖型地中海贫血患者的独特需求而量身定制的。这种新方案的交付是可行的,并显示出良好的早期植入和移植结果。在推广之前,需要对该队列进行进一步随访并扩大患者数量,但早期经验是有希望的。
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Early Engraftment and Immune Kinetics Following Allogeneic Transplant Using a Novel Reduced-Toxicity Transplant Strategy in Children/Adolescents with High-Risk Transfusion-Dependent Thalassemia: Early Results of the ThalFAbS Trial
Allogeneic hematopoietic stem cell transplantation is challenging for patients with transfusion-dependent thalassemia who have experienced iron overload and received chronic transfusion support. A transplantation strategy including a reduced-intensity preparative regimen and tailored immunosuppression to support donor engraftment and prevent graft-versus-host disease (GVHD) was developed for this population. The combination of a pretransplantation immunosuppression phase with reduced dosing of fludarabine/prednisone, a treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/antithymocyte globulin was tested. In the ThalFAbS trial, a prospective pilot trial (ClinicalTrials.gov NCT05426252) of a transplantation strategy designed for higher-risk patients with transfusion-dependent thalassemia, 12 pediatric patients (4 with alpha thalassemia, 8 with beta thalassemia) were treated with this strategy. Descriptive statistics were used to characterize transplantation outcomes and immune recovery. With a median follow-up of 12 months (range, 4 to 26 months) post-transplantation, all 12 patients had prompt and durable trilineage donor engraftment with low transplantation-related morbidity and acute GVHD and are alive without transfusion support at the time of this report. GVHD was limited to 1 patient with skin-only grade II acute GVHD and 3 patients with limited oral chronic GVHD. Early hematologic and immunologic recovery was achieved, with low rates of transfusion support and infection. Neutrophil recovery occurred at a median of 18 days (range, 15 to 24 days), and platelet recovery occurred at a median of 18 days (range, 12 to 36 days). No patients experienced veno-occlusive disease, transplantation-associated thrombotic microangiopathy, or sepsis. This platform was sufficient to support haploidentical donor transplantation in 2 patients. The ThalFAbS approach is tailored to meet the unique needs of transfusion-dependent thalassemia patients. Delivery of this novel regimen is feasible, and it shows excellent early engraftment and transplantation outcomes. Further follow-up of this cohort and expansion of patient numbers is needed before the findings can be generalized, but early experience is promising.
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CiteScore
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自引率
15.60%
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期刊最新文献
INFECTIOUS ENTEROCOLITIS IN HEMATOPOIETIC CELL TRANSPLANT WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE. Best Practices in Gene Therapy for Sickle Cell Disease and Transfusion-dependent β-Thalassemia. Outcome of Patients with IDH-mutated AML following Allogeneic Stem Cell Transplantation - a Retrospective Analysis on behalf of the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy, DRST. Temporal evolution of functional immune reconstitution after allogeneic HSCT. Clinical Outcome of UCBT for Children with CAEBV: A Retrospective Analysis of a Single Center.
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