ATG联合PTCy的Haplo-HSCT方案治疗儿童骨髓增生异常综合征

Clinical Efficacy of Haplo-HSCT of ATG Combined with PTCy for Children with Myelodysplastic Syndrome

目的:探讨ATG联合后置环磷酰胺(PTCy)诱导免疫耐受的单倍体型造血干细胞移植(haplo-HSCT)方案治疗儿童骨髓增生异常综合征(MDS)的疗效及安全性。方法:回顾并分析2016年7月至2020年11月在本中心接受ATG联合PTCy诱导免疫耐受的Haplo-HSCT方案治疗的8例儿童MDS患者的临床资料。结果:8例儿童MDS患者中,男1例,女7例,中位年龄6.4岁(10个月-15岁),病史中位数2.7年(3个月-8年),7例诊断为难治性血细胞减少症,1例诊断为难治性贫血伴原始细胞增多。供者为患者父亲、母亲或哥哥,HLA配型(6-9)/12位点相合,供者经筛查均为健康供者,未携带受者致病基因,中位年龄36.4(25-49)岁,回输单个核细胞中位数19.8(13.2-47.3)×10^(8)/kg, CD34^(+)细胞中位数11.8(5.0-18.3)×10^(6)/kg。移植后3至4 d予环磷酰胺(Cy/CTX)50 mg/(kg·d)静脉滴注,移植后5 d起予小剂量他克莫司(FK506)静脉滴注、吗替麦考酚酯(MMF)口服预防移植物抗宿主病。粒细胞和血小板植入时间分别为12.6(11-15)和13.3(11-18)d,所有患者在植入时均获得完全的供体细胞嵌合。中位随访时间为1032(747-1536)d,总体生存率及无病生存率均为100%。结论:ATG联合PTCy诱导免疫耐受的Haplo-HSCT方案是治疗儿童MDS安全有效的方法。

Objective: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation( haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide( PTCy)-induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes( MDS). Methods: From July 2016 to November2020,a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled,whose clinical data were retrospected and analyzed.Results: Median age at diagnosis of the 8 children( 1 male and 7 females) was 6. 4( range,10 months to 15 years)years old. The median medical history of MDS w as 2. 7 years( range,3 months to 8 years). Among the 8 patients,7 cases were diagnosed with refractory cytopenia of childhood and one w ith refractory anemia w ith excess of blasts. The HSC donors w ere father,mother or brother of patients and HLA matching in 6-9/12 loci w ere identical. All the donors w ere healthy and didn’t carry the same pathogenic genes as the recipients. The median age of donors w as 36. 4( range,25 to 49) years old. The median mononuclear cell( M NC) number of the graft w as 19. 8,ranging in( 13. 2-47. 3) ×10^(8)/kg,and the median CD34^(+)cell number w as 11. 8 × 10^(6)/kg,ranging in( 5. 0-18. 3) × 106/kg. Graft-versus-host disease prophylactic regimen w as started on day 3 and 4 after transplantation,in which cyclophosphamide( 50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation,low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil w as administered orally. The median time of neutrophil and platelet engraftment was 12. 6( rang,11 to 15) days and 13. 3( rang,11 to 18) days,respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time w as 1 032( rang,747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%. Conclusion: Haplo-HSCT combined w ith ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.