【摘要】 目的探讨改良后置环磷酰胺体系下异基因单倍型造血干细胞移植治疗幼年型粒单核细胞型白血病(juvenile myelomonocytic leukemia,JMML)的疗效及其影响因素。方法选取本院6例确诊JMML患儿,男3例,女3例,所有患儿在移植前均接受一轮去甲基化药物治疗,其中5例患儿预处理方案采用白舒非+氟达拉滨+阿糖胞苷,1例患儿采用白舒非+氟达拉滨+美法仑。预防移植物抗宿主病(graft-versus-host disease,GVHD)方案:移植后3~4天予50mg/kg环磷酰胺静脉滴注,联合短疗程甲氨蝶呤,移植后5天起予他克莫司静脉滴注、口服吗替麦考酚酯。结果 5例患者成功植入造血干细胞,其中1例移植后6个月复发死亡,其余4例至今无病生存,另1例出现原发性植入失败,血象自行恢复,目前无病生存。移植前疾病负荷、携带基因突变情况及Ⅱ~IV度急性移植物抗宿主病(acute graft-versus-host disease,a GVHD)的发生均与JMML的复发率及无病生存率相关;移植前去甲基化治疗方案优于单纯预处理方案;HLA相合度不影响总的生存率及无病生存率;移植年龄(>2岁)、移植前血小板数小于40×109/L及存在PTPN11基因突变对移植复发率均有重要影响;采用后置环磷酰胺体内去除活化T淋巴细胞的GVHD预防方案,移植后能够迅速撤掉免疫抑制剂,有利于移植后免疫功能重建,可减少感染发生率及移植复发率。结论异基因单倍型造血干细胞移植联合后置环磷酰胺是治疗JMML的有效方法,但尚需大宗病例进一步证实。更多还原

【Abstract】 Objective This study was purposed to explore the therapeutic efficacy and influencing factors of haploidentical stem cell transplantation(HSCT) with post-transplant cyclophosphamide(PTCy) in patients diagnosed with juvenile myelomonocytic leukemia(JMML). Method Six patients diagnosed as JMML including 3 boys and 3 girls were selected at the time of transplantation. All patients were given a demethylation therapy pre-transplantation. Among of them, 5 children proceed with BU+FLU+Ara-C as conditioning regimen, another accepted BU+FLU+Mel as conditioning regimen. Graft-versus-host disease(GVHD) prophylaxis: followed by post-transplant CY(50 mg/kg/day on day +3 and +4). Low dose of tacrolimus and mycophenolate mofetil was commenced on day +5 and was tapered off by day +90 if there was no GVHD. The donors were their HLA-haploidentical father or mother. Result The results showed that hematopoietic stem cells in 6 patients grafted successfully, one patient occurred primary graft failure, blood routine recovered itself and still alive without disease. Another patient died of relapse of disease post 6 months allo-HSCT. The analysis found that the disease burden before transplant, poor risk gene type, a GVHD Ⅱ-Ⅳ all associated with the relapse rate and disease-free survival rate of JMML. Demethylation therapy before allo-HSCT was better than simply conditioning regimen. Type of donor and source of stem cells did not statistically and significantly affect OS and DFS. Older age at diagnosis(>2 years), platelets less than 40×109/L and PTPN11 mutation were these factors significantly associated with shorter survival time. Our studies did not show higher risk relapse in patients with JMML underwent allo-HSCT combined with post-transplant cyclophosphamide, and in contrast, after PTCy,immunosuppressive could be tapped off quickly and reduced the rate of infection and with a rapid of immune recovery. Conclusion Allo-HSCT with PTCy is an effective regimen for JMML, large cases are still needed for further confirmation.更多还原