二次互补性移植联合地西他滨治疗幼年型粒单核细胞白血病1例

Twice complementary transplantation combined with decitabinefor one child with juvenile myelomonocytic leukemia

目的探讨单倍体+无关不全相合脐血互补性移植联合地西他滨治疗幼年型粒单细胞白血病(JMML)的安全性和有效性。方法 4岁患儿采用单纯地西他滨治疗后[20mg/(m^2·d)×5d为1个疗程,共2疗程,间隔4周]桥接第一次母亲单倍体(5/10)+无关脐血(7/10)互补移植,植入失败后50d改用第二次同胞单倍体(5/10)+第二份无关脐血(7/10)互补移植进行挽救;移植预处理方案以Cy+Flu+BU为基础,使用PT-Cy并序贯MMF、FK506、CsA组合的预防GVHD方案;移植后继续使用地西他滨[5～10mg/(m^2·d)×5d]4个疗程(疗程间间隔4～6周)作为维持治疗,以清除"免疫逃逸"之白血病瘤细胞。结果随访时间15个月,第一次移植后+45d发生原发性植入失败;二次移植为独立脐血植入,粒细胞植入时间为二次移植后的+71d,血小板植入时间为+105d,第二次移植后20天并发重度aGVHD(肠道3级,皮肤2级),给予静脉FK506+MMF+MP抗GVHD治疗后均得到控制,未发生慢性GVHD。移植后使用地西他滨期间未见明显肝肾毒性,未发生严重骨髓抑制(粒细胞大于0.5G/L)。6个月后逐渐停服免疫抑制剂,无病存活至今。结论单倍体+无关不全相合脐血互补移植联合地西他滨治疗JMML是安全有效的,移植前适当的化疗对于HLA不全相合的移植而言可能是必要的。

Objective To investigate the safety and efficacy of complementary transplantation（CT） （unrelated cord blood following haploidentical stem cells ） combined with decitabine for Juvenile Myelomonocytic Leukemia （JMML）. Methods A 4 years-old child was treated with two courses of decitabine [ 20 mg/（ m2 · d） × 5d for each course with 4 weeks interval ] alone as ＂bridging therapy＂ before the first CT from mother haploid （HLA 5/10） and unrelated cord blood （UCB） （HLA 7/10） donor. He accepted a salvaged transplantation from sibling haploid （5/10） and another UCB （7/10） donor when primary engraftment failure occurred on 50th day after first CT. GVHD prophylaxis was consisted of PT-Cy, MMF and FKS06/CsA. Decitabine was administrated as maintenance therapy for 4 courses [ 5 - 10mg/（m2· d） × 5d for each course with the interval of 4 - 6 weeks ] after HSCT to overcome immune-escape of leukemia cells. Results The follow-up time was 15 months. Donor cells＇ primary engraftment failure occurred after 45 days of the first transplantation. UCB-donor cells engrafted fully in the patient after the second transplantation. The times to neutrophil more than 0.5 × 10 9/L and platelet more than 20 × 10 9/L were 71 days and 105 days post- second transplantation. Severe aGVHD （intestinal grade 3, skin grade 2 ） was observed on 20th day post-transplant and controlled by anti-GVHD treatment with intravenous FKS06, MMF and MP. No cGVHD was happened. No significant hepatorenal toxicity was observed during the use of decitabine after transplantation. Especially, no severe bone marrow suppression occurred （granulocytes less than 0.5 ×10 9/L）. Conclusions Complementary Transplantation （haploid following UCB transplantation） combined with Decitabine for JMML is safe and effective. Proper chemotherapy before transplantation may be necessary for HLA-mismatch HSCT.