Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been accepted as a treatment option for aggressive (acute or lymphoma type) adult T cell leukemia/lymphoma (ATLL) patients with a poor prognosis, when a suitable HLA-matched donor is not available. However, haplo-HSCT carries a potential risk of treatment-related mortality including severe graft-versus-host disease (GVHD). Therefore, we conducted a prospective pilot study in order to evaluate the efficacy and safety of reduced-intensity haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with low-dose thymoglobulin (2.5 mg/kg only on day -2), fludarabine, melphalan, and total body irradiation 4 Gy for aggressive ATLL. Three consecutive acute type ATLL patients, who were ineligible for conventional myeloablative conditioning due to advanced age or comorbidities, were enrolled. One patient received pretransplant mogamulizumab therapy. All the patients were not in complete remission (CR) at the time of transplantation. Our transplantation protocol was safely carried out. CR was achieved in all the patients after transplantation. HTLV-I viral loads became undetectable after transplantation. No severe adverse events such as grade III-IV GVHD or viral/fungal diseases were observed. At a follow-up of 2 years, they were still in CR. However, T cell receptor repertoire diversities were low 1 year after transplantation in next-generation sequencing. Our results show encouraging therapeutic benefits of this pilot approach using reduced-intensity haplo-PBSCT with low-dose thymoglobulin for aggressive ATLL patients.

中文翻译：

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使用低剂量胸腺球蛋白降低强度的单倍体外周血干细胞移植，用于未完全缓解的侵袭性成人T细胞白血病/淋巴瘤患者。

当没有合适的HLA匹配供体时，单倍型造血干细胞移植（haplo-HSCT）已被接受为预后较差的侵袭性（急性或淋巴瘤型）成人T细胞白血病/淋巴瘤（ATLL）患者的治疗选择。但是，单倍HSCT可能带来与治疗相关的死亡风险，包括严重的移植物抗宿主病（GVHD）。因此，我们进行了一项前瞻性先导研究，以评估低剂量胸腺球蛋白（仅在第2天仅2.5 mg / kg），氟达拉滨，低剂量单倍外周血干细胞移植（haplo-PBSCT）的疗效和安全性。美法仑，全身照射4 Gy用于积极的ATLL。连续三例急性ATLL患者，入选了因年龄大或合并症而不能进行常规清髓治疗的患者。一名患者接受了移植前莫加莫珠单抗治疗。所有患者在移植时均未完全缓解（CR）。我们的移植方案已安全执行。移植后所有患者均达到CR。HTLV-1病毒载量在移植后变得不可检测。没有观察到严重的不良事件，如III-IV级GVHD或病毒/真菌病。经过2年的随访，他们仍处于CR中。然而，在下一代测序中，移植后1年T细胞受体库的多样性很低。我们的研究结果表明，使用积极的ATLL患者使用低剂量的单倍剂量的PBSCT和低剂量的胸腺球蛋白，这种试验方法具有令人鼓舞的治疗益处。