应用改良BU/CY方案预处理联合自体外周血造血干细胞移植治疗青年中、低危急性髓系白血病疗效观察

Clinical Efficacy of Modified BU/CY as Conditioning Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Young Acute Myeloid Leukemia Patients with Low or Intermediate Risk

目的:观察青年中、低危急性髓系白血病(AML)在第1次完全缓解期(CR1)接受白消安(BU)/环磷酰胺(CY)改良方案预处理后行自体外周血造血干细胞移植(auto-PBHSCT)的安全性及疗效。方法:采用回顾性分析方法探讨改良BU/CY预处理联合auto-PBSCT的疗效。本院2013年5月至2016年12月期间10例青年中、低危AML患者,无异基因干细胞移植条件、CR1期接受以改良的BU/CY方案预处理联合auto-PBSCT,移植后3个月开始白介素-2(IL-2)或IL-2+二盐酸组胺维持治疗18个月。观察预处理方案的毒副作用、造血恢复时间、移植后100 d及1年内死亡率、复发率、2年及3年无白血病生存率(LFS)、3年及4年总生存率(OS)。结果:常见的非血液学毒性反应为胃肠道反应(轻度7例、中度3例、重度1例)、轻度肝损害(4例)、出血性膀胱炎0例、轻中度感染10例(血流感染5例,肠道感染2例,肛周感染3例,口腔感染2例)。患者均达到清髓效果,中性粒细胞(ANC)<0.5×10~9/L中位时间为1.5(0-3 d)d,血小板(Plt)<20×10~9/L中位时间为3(2-5)d。移植后中性粒细胞植入中位时间为13(10-19)d,血小板植入中位时间为32(10-72)d。移植后100 d及1年内死亡率为0。1例移植后半年复发,1例移植后14个月复发。移植后中位随访时间48.1个月,至随访日中位生存时间54.7个月。2年LFS为100%(10例),3年LFS为80%(8例);3年OS为80%(8例),4年OS为70%(7例)。结论:改良的BU/CY+auto-PBSCT治疗模式可达到清髓目的,对青年中、低危AML疗效明确,移植相关死亡率低,LFS及OS时间较长,可作为无异基因造血干细胞移植条件患者的另一个治疗选择。

Objective:To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT)using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission(CR1).Methods:Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation(allo-HSCT)and underwent autoPBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed.From 3 months after autoPBHSCT,the maintenance therapy with interleukin-2(IL-2)or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months.The side effects of the conditioning regimen,hematopoietic recovery time,transplant-related mortality(TRM)within 100 days and 1 year after auto-PBHSCT,relapse rate,leukemiafree survival(LFS)rate at 2 years and 3 years,overall survival(OS)were evaluated at 3 years and 4 years.Results:Gastrointestinal side effects were the major non-hematologic toxicity reaction,among which,7 cases relatively mild and 3 cases displayed moderate,just one case suffered from severe reaction.In 4 cases,the mild liver damage occurred,but no hemorrhagic cystitis occurred.All the patients experienced different kinds of infection,including 5 cases of bloodstream infection,2 cases of gastrointestinal infection,3 cases of crissum infection and 2 cases of oral infection.The myeloablative effect occurred in all ten patients.The median times for absolute neutrophil count(ANC)<0.5×10^9/L and for platelet count<20.0×10^9/L were 1.5(0-3)days and 3(2-5)days after transplantation,respectively.The patients achieved ANC>0.5×10^9/L at 10 to 19 days,median was 13 days after auto-PBHSCT.The patients achieved platelet count>20×10^9/L at 10 to 72 days;median was 32 days after auto-PBHSCT.The TRM within 100 days and 1 year after transplantation was 0.The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively.The median follow-up time was 48.1 months,and the median survival time was 54.7 months after transplantation.The 2-year and 3-year LFS were 100%(10 cases)and 80%(8 cases),respectively.The 3-year and 4-year OS were 80%(8 cases)and70%(7 cases),respectively.Conclusion:Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS.As for young AML patients without high risk,it is a valuable therapeutic option,especially for those lacking the chance of allo-HSCT.