Umbilical Cord Blood Transplantation Using Reduced-intensity Conditioning without Antithymocyte Globulin in Adult Patients with Severe Aplastic Anemia
Umbilical Cord Blood Transplantation Using Reduced-intensity Conditioning without Antithymocyte Globulin in Adult Patients with Severe Aplastic Anemia
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在患有严重再生障碍性贫血的成年患者中使用不使用抗胸腺细胞球蛋白的降低强度预处理进行脐带血移植
DOI：
10.1016/j.bbmt.2018.09.039
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Harigae H
中科院分区：
文献类型：
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作者：
Ochi T;Onishi Y;Nasu K;Onodera K;Kobayashi M;Ichikawa S;Fujiwara T;Fukuhara N;Yamada-Fujiwara M;Harigae H
脐带血移植（UCBT）是没有相关或不相关HLA匹配供体的再生障碍性贫血（AA）患者的一种可能选择，特别是在免疫抑制治疗（IST）失败或迫切需要移植的情况下。然而，UCBT后移植失败率较高仍然是一个主要问题，UCBT后稳定植入的最佳预处理方案尚未建立。在此，我们研究了6例接受UCBT的成年AA患者，采用的是低强度预处理（RIC）方案，包括氟达拉滨125 mg/m2、环磷酰胺120 mg/kg和4戈伊全身照射（Flu/CY/TBI 4戈伊），无抗胸腺细胞球蛋白（ATG）。5例患者在IST失败后接受了UCBT，1例患者接受了UCBT作为一线治疗，原因是尽管给予了粒细胞集落刺激因子，但中性粒细胞计数为0的暴发性临床结果。关于移植物抗宿主病（GVHD）预防，2例患者接受他克莫司联合短期甲氨蝶呤治疗，4例患者接受他克莫司联合吗替麦考酚酯治疗，所有患者均实现中性粒细胞和血小板持续植入，中位植入时间为17.5天在所有患者中，完全供体嵌合体在中位数14天（范围，14至32天）时得到证实。3例患者发生II级急性GVHD（aGVHD），但未观察到III/IV级aGVHD，而4例患者发生仅累及皮肤的慢性GVHD。在本报告时，所有6例患者均存活，无需输血，中位随访时间为16个月（范围：12至131个月）。虽然还需要进一步的研究，我们的研究结果表明，与流感/CY/TBI 4Gy无ATG预处理可能会允许稳定的植入在UCBT成人AA。
Umbilical cord blood transplantation (UCBT) is a possible option for patients with aplastic anemia (AA) without a related or unrelated HLA-matched donor, particularly if immunosuppressive therapy (IST) has failed or transplantation is urgently needed. However, a higher rate of graft failure after UCBT remains a major problem, and the optimal conditioning regimen for stable engraftment after UCBT has not been established. Here we investigated 6 adult patients with AA who underwent UCBT using a reduced-intensity conditioning (RIC) regimen comprising fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and 4 Gy of total body irradiation (Flu/CY/TBI4Gy) without antithymocyte globulin (ATG). Five patients underwent UCBT after IST failure, and 1 patient underwent UCBT as a first-line treatment due to a fulminant clinical finding of a neutrophil count of 0, despite granulocyte colony-stimulating factor administration. Regarding graft-versus-host disease (GVHD) prophylaxis, 2 patients received tacrolimus plus short-term methotrexate and 4 patients received tacrolimus plus mycophenolate mofetil, and all patients achieved sustained engraftment of both neutrophils and platelets, at a median of 17.5 days (range, 14 to 37 days) and 38.5 days (range, 31 to 86 days), respectively, with complete donor chimerism confirmed in all patients at a median of 14 days (range, 14 to 32 days). Three patients developed grade II acute GVHD (aGVHD), but grade III/IV aGVHD was not observed, whereas 4 patients developed chronic GVHD involving only skin. At the time of this report, all 6 patients were alive without the need for blood transfusion, at a median follow-up of 16 months (range, 12 to 131 months). Although further study is needed, our findings suggest that conditioning with Flu/CY/TBI4Gy without ATG might allow stable engraftment in UCBT for adults with AA.