Early administration of cyclosporine may reduce the incidence of cytokine release syndrome after HLA-haploidentical hematopoietic stem-cell transplantation with post-transplant cyclophosphamide
Early administration of cyclosporine may reduce the incidence of cytokine release syndrome after HLA-haploidentical hematopoietic stem-cell transplantation with post-transplant cyclophosphamide
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DOI：
10.1007/s00277-021-04439-6
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发表时间：
2021-02-12
影响因子：
3.5
通讯作者：
Chiba, Shigeru
中科院分区：
文献类型：
--
作者：
Kurita, Naoki;Sakamoto, Tatsuhiro;Chiba, Shigeru
细胞因子释放综合征（CRS），发生在70%以上的HLA半相合造血干细胞移植与移植后环磷酰胺（PT/CY-haplo），可导致血流动力学不稳定和恶化的临床结果。在常用的PT/CY方案中，在环磷酰胺给药后开始使用钙调磷酸酶抑制剂。在此，我们进行了一项I/II期、前瞻性、单中心PT/CY-haplo试验，以评价沿着第3天和第5天环磷酰胺与第-1天开始的环孢菌素和吗替麦考酚酯的安全性和有效性。入组了35名患有恶性血液病的成年人。分别在25例和10例患者中使用了清髓性和低强度预处理。11例患者的移植物来源为骨髓，24例患者的移植物来源为动员的外周血干细胞。第100天的无病生存率（主要终点）为86%（95%置信区间（CI），69-94），超过预定义的阈值50%。出乎意料的是，仅20%（95%CI，8.4-37）的患者在移植物输注后早期出现> 38 ° C的发热，所有CRS均为1级，并且所有这些均在环磷酰胺施用后立即消退。II-IV级急性移植物抗宿主病（GVHD）、III-IV级急性GVHD和中重度慢性GVHD的累积发生率分别为23%（95% CI，11-38）、6%（95% CI，1-17）和11%（95% CI，4-25）。3年总生存率为49%（95%CI，31-64）。我们的研究结果表明，在PT/CY之前给予环孢素和霉酚酸酯可以降低CRS的频率和严重程度，而不会增加GVHD。UMIN临床试验注册编号：000006631和000015694
Cytokine release syndrome (CRS), occurring in more than 70% of HLA-haploidentical hematopoietic stem-cell transplantations with post-transplant cyclophosphamide (PT/CY-haplo), can lead to hemodynamic instability and worsen clinical outcomes. A calcineurin inhibitor is initiated after cyclophosphamide administration in the commonly used PT/CY regimens. Here, we conducted a phase I/II, prospective, single-center trial of PT/CY-haplo to evaluate the safety and efficacy of cyclophosphamide on days 3 and 5 along with cyclosporin and mycophenolate mofetil started from day - 1. Thirty-five adults with hematologic malignancies were enrolled. Myeloablative and reduced-intensity conditioning were used in 25 and 10 patients, respectively. Graft sources were bone marrow in 11 patients and mobilized peripheral blood stem cells in 24 patients. Disease-free survival on day 100, the primary endpoint, was 86% (95% confidence interval (CI), 69-94), which was over the predefined threshold of 50%. Unexpectedly, only 20% (95% CI, 8.4-37) of patients developed fever of > 38 degrees C early after graft infusion, all CRS grade 1, and all of which resolved just after cyclophosphamide administration. The cumulative incidences of grades II-IV acute graft-versus-host disease (GVHD), III-IV acute GVHD, and moderate-severe chronic GVHD were 23% (95% CI, 11-38), 6% (95% CI, 1-17), and 11% (95% CI, 4-25), respectively. The 3-year overall survival rate was 49% (95% CI, 31-64). Our results suggest that administration of cyclosporine and mycophenolate mofetil prior to PT/CY can reduce the frequency and severity of CRS without increasing GVHD. UMIN Clinical Trial Registry numbers: 000006631 and 000015694