Reduced-intensity haploidentical peripheral blood stem cell transplantation using low-dose thymoglobulin for aggressive adult T cell leukemia/lymphoma patients in non-complete remission.
Reduced-intensity haploidentical peripheral blood stem cell transplantation using low-dose thymoglobulin for aggressive adult T cell leukemia/lymphoma patients in non-complete remission.
复制标题
使用低剂量胸腺球蛋白进行降低强度单倍相合外周血干细胞移植，用于治疗未完全缓解的侵袭性成人 T 细胞白血病/淋巴瘤患者。
DOI：
10.1007/s00277-020-03934-6
复制
发表时间：
2020
期刊：
影响因子：
3.5
通讯作者：
Tsukada J.
中科院分区：
文献类型：
--
作者：
Hirosawa M;Yamaguchi T;Tanaka A;Kominato Y;Higashi T;Morimoto H;Tsukada J.
单倍体造血干细胞移植（haploo - hsct）已被接受为预后不良的侵袭性（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，当没有合适的hla匹配供体时。然而，单倍造血干细胞移植具有治疗相关死亡率的潜在风险，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天使用2.5 mg/kg）、氟达拉滨、美法兰和4 Gy全身照射治疗侵袭性ATLL的低强度单倍体外周血干细胞移植（haploo - pbsct）的有效性和安全性。3例连续急性ATLL患者，由于高龄或合并症不适合常规清髓治疗。1例患者接受移植前mogamulizumab治疗。所有患者在移植时均未完全缓解（CR）。我们的移植方案是安全执行的。所有患者移植后均达到CR。移植后无法检测到HTLV-I病毒载量。未观察到严重不良事件，如III-IV级GVHD或病毒/真菌疾病。在2年的随访中，他们仍然处于CR状态。然而，在下一代测序中，移植后1年的T细胞受体库多样性较低。我们的研究结果显示，使用低剂量胸腺球蛋白的低强度单倍pbsct治疗侵袭性ATLL患者的试验方法具有令人鼓舞的治疗效果。
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.