Department of Hematology/Oncology, Osaka Women's and Children's Hospital, 840 Murodo, Izumi city, Osaka, 594-1101, Japan.
Int J Hematol. 2022 Feb;115(2):269-277. doi: 10.1007/s12185-021-03254-z. Epub 2021 Nov 5.
Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m, melphalan (MEL) 210 mg/m, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.
移植物失败是儿童罕见血液疾病（除急性白血病外）进行非亲缘脐带血移植（CBT）的主要问题，例如获得性和遗传性骨髓衰竭、骨髓增生异常综合征、青少年骨髓单核细胞白血病和慢性髓性白血病。我们为 CBT 开发了一种毒性较小的预处理方案，可实现更高的完全供体嵌合率，并在我们的单机构中回顾性比较了该方案与其他两种 CBT 预处理方案。使用我们最新的包含氟达拉滨（Flu）180mg/m2、马利兰（MEL）210mg/m2 和低剂量兔抗胸腺细胞球蛋白（LD-rATG）2.5mg/kg 的低强度预处理（RIC）方案（无照射）（方案 C）的 11 名患者的嵌合率为 100%，5 年无事件生存率（5y-EFS）为 90.9%。结果优于接受含照射的先前方案（5y-EFS 30.0%，p=0.004）的患者：方案 A 为含环磷酰胺（CY）和全身照射（TBI）的 8-12Gy 的清髓预处理，或方案 B 为含 Flu、CY、马 ATG 和 6Gy 胸腹部照射（TAI）的 RIC。总之，无 TBI/TAI 的 Flu/MEL/LD-rATG（方案 C）可能是儿童罕见血液疾病进行非亲缘 CBT 的 RIC 的首选方案。
