Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease
Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease
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DOI：
10.1182/bloodadvances.2020002236
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发表时间：
2020-08-25
期刊：
影响因子：
7.5
通讯作者：
Shenoy, Shalini
中科院分区：
文献类型：
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作者：
Ngwube, Alexander;Shah, Niketa;Shenoy, Shalini
我们报道了一项多中心干细胞移植(SCT)试验的结果，该试验采用骨髓或脐带血作为干细胞来源，对7例人类白细胞抗原相合或1个抗原不相合的非血缘关系供者进行了一期多中心干细胞移植(SCT)治疗重症镰状细胞病(SCD)。条件化包括远端阿仑珠单抗、氟达拉滨和马法兰(匹配供者)，以及硫替巴(不匹配供者)。他克莫司和甲氨蝶呤作为移植物抗宿主病(GVHD)的预防药物被加入T细胞共刺激的选择性抑制剂阿巴替康中，以抵消移植物抗宿主病(GVHD)的风险，并且由于骨髓慢性GVHD的发生率增加，在骨髓受者中的服药时间比脐血受者更长。移植时的中位年龄为13岁(7-21岁)。+100d时II~IV级和III~IV级急性移植物抗宿主病的发生率分别为28.6%和7%。慢性移植物抗宿主病的一年发病率为57%，除1名接受较长时间阿巴贝特治疗的患者外，其余患者均为轻度/局限性。仅1例发生可逆性后脑病综合征并痊愈。中位随访期为1.6年(1~5.5年)，2年总生存率为100%，无瘤生存率为92.9%。尽管存在高龄、URD和人类白细胞抗原不匹配等危险因素，RIC SCT试验第一阶段的令人鼓舞的结果支持了URD SCT在临床试验环境中的进一步评估。试验的第二阶段正在进行中。
We report results of a phase 1 multicenter stem cell transplantation (SCT) trial from HLA-matched (n = 7) or one-antigen-mismatched (n = 7) unrelated donors (URD) using bone marrow or cord blood as stem cell source, following reduced-intensity conditioning (RIC) in severe sickle cell disease (SCD). Conditioning included distal alemtuzumab, fludarabine, and melphalan (matched donors), with thiotepa (mismatched donors). Abatacept, a selective inhibitor of T cell costimulation, was added to tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis to offset GVHD risks, and was administered for longer duration in bone marrow recipients than in cord blood recipients because of increased incidence of chronic GVHD with bone marrow. Median age at transplant was 13 years (range, 7-21 years). The incidence of grades II to IV and grades III to IV acute GVHD at day +100 was 28.6% and 7%, respectively. One-year incidence of chronic GVHD was 57% and mild/limited in all but 1 patient who received abatacept for a longer duration. Only 1 patient developed reversible posterior encephalopathy syndrome and recovered. With a median follow-up of 1.6 years (range, 1-5.5 years), the 2-year overall and disease-free survival was 100% and 92.9%, respectively. The encouraging results from the phase 1 portion of this RIC SCT trial, despite risk factors such as older age, URD, and HLA-mismatch, support further evaluation of URD SCT in clinical trial settings. The phase 2 portion of the trial is in progress.