Takpradit Chayamon, Prockop Susan E, Kernan Nancy A, Scaradavou Andromachi, Curran Kevin, Ruggiero Julianne, Zakak Nicole, O'Reilly Richard J, Boulad Farid
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center.
Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
J Pediatr Hematol Oncol. 2018 May;40(4):e220-e224. doi: 10.1097/MPH.0000000000001106.
The combination of cyclophosphamide (CY) and antithymocyte globulin (ATG) has been used as a standard conditioning regimen for matched related donor transplantation in patients with severe aplastic anemia.
To decrease the regimen-related toxicity while maintaining appropriate engraftment and survival rates, fludarabine (FLU) was added to the regimen. Four pediatric patients received matched related donor bone marrow transplantation with CY (50 mg/kg×2) (instead of the 50 mg/kg×4 standard dosing), equine ATG (30 mg/kg×3), with the addition of FLU (30 mg/m×4). Graft versus host disease (GvHD) prophylaxis included a calcineurin inhibitor and methotrexate.
No grade 4 acute toxicities occurred during the first 30 days after transplant. All patients engrafted with normalization of peripheral blood counts and transfusion independence. One patient developed grade 1 to 2 acute GvHD, followed by chronic GvHD that resolved. With a median follow-up of 41.7 months, all 4 patients are alive and transfusion free, with complete donor chimerism. This combination of a low-dose CY/ATG+FLU regimen was overall very well tolerated and contributed toward a successful outcome including engraftment, chimerism, and survival.
This small pilot study shows that this cytoreductive regimen could be considered as the standard of care for transplantation of pediatric patients with aplastic anemia from HLA-matched siblings.
环磷酰胺（CY）与抗胸腺细胞球蛋白（ATG）联合使用，一直是重型再生障碍性贫血患者进行匹配相关供体移植的标准预处理方案。
为降低方案相关毒性，同时维持适当的植入率和生存率，在该方案中加入了氟达拉滨（FLU）。4例儿科患者接受了匹配相关供体骨髓移植，使用CY（50mg/kg×2）（而非标准剂量50mg/kg×4）、马抗胸腺细胞球蛋白（30mg/kg×3），并加入FLU（30mg/m×4）。移植物抗宿主病（GvHD）预防措施包括使用钙调神经磷酸酶抑制剂和甲氨蝶呤。
移植后前30天内未发生4级急性毒性反应。所有患者外周血细胞计数恢复正常并实现输血独立。1例患者发生1至2级急性GvHD，随后慢性GvHD得到缓解。中位随访41.7个月时，所有4例患者均存活且无需输血，具有完全供体嵌合。低剂量CY/ATG+FLU方案总体耐受性良好，有助于实现包括植入、嵌合和生存在内的成功结局。
这项小型试点研究表明，这种细胞减灭方案可被视为HLA匹配同胞的再生障碍性贫血儿科患者移植的标准治疗方案。
