供者干细胞输注治疗慢性髓性白血病异基因造血干细胞移植后的复发——1例报告及文献复习

Treatment of donor stem cell infusion for relapse of leukemia after allogeneic hematopoietic stem cell transplantation-one case report and literature review

目的:探索异基因造血干细胞移植(Allo-HSCT)后白血病复发的供者干细胞输注治疗方法,提高Allo-HSCT的疗效。方法:慢性髓性白血病-慢性期(CML-CP)患者1例,采用改良的白消安/环磷酰胺(BU/CY)方案预处理。回输HLA配型相合的胞兄的外周血干细胞,单个核细胞(MNC)3.42×108/kg,CD34+细胞3.82×106/kg。移植物抗宿主病(GVHD)的预防采用环胞素A(CsA)联合短疗程甲氨蝶呤(MTX)方案,移植后6个月停用CsA。+192d细胞遗传学复发,给予未经动员的供者淋巴细胞输注(DLI),细胞剂量为1.8×107MNC/kg。+458d血液学复发,给予联合化疗加经粒细胞集落刺激因子(G-CSF)动员的供者干细胞输注(DSI),细胞剂量为4.68×108MNC/kg。结果:移植后+13d白细胞植活,+16d血小板植活,+20d短串联重复序列(STR-PCR)检测显示为完全供者的基因型,同时Ph染色体及bcl/abl融合基因转为阴性。于+182d发生了肝脏及皮肤的慢性移植物抗宿主病(cGVHD),未使用免疫抑制剂的情况下,cGVHD逐渐消失。+192d细胞遗传学复发予DLI后完全缓解(CR)。+458d血液学复发,予联合化疗加DSI后再次达CR。随访至今,患者于Allo-HSCT后567d,DSI后79d仍无病存活。结论:DLI≤0.2×108MNC/kg是安全有效的。在血液学水平复发的患者,单用化疗或DLI疗效有限,联合化疗加DSI可使疗效提高,且无明显的并发症发生。

Objeetive：To explore the treatment of donor stem cell infusion for relapse of leukemia after allogeneic hematopoietic stem cell transplantation（Allo-HSCT） and improve curative effect on Allo-HSCT. Method： A 30 year old patient（male） with CML-CP received Allo-HSCT from HLA-identical sibing donor. The conditioning regimen was modified BU/CY. 3.42 × 10^8MNC/kg, 3.82 × 10^6 CD34^＋ cells/kg were transplanted. The prophylaxis regiment of graft-versus host disease（GVHD） was the combination of cyclosporine（CsA） and short course methotrexate（MTX）. CsA was stopped after 6 months after transplantation. The cytogeneic relapse occurred on ＋192 d, and donor lymphocyte infusion（DLI） without mobilization was given to him. The cell dose was 1.8×10^7 MNC/kg. The haematological relapse occurred on ＋458 d, and the combination of chemical treatment and donor stem cell infusion（DSI） with mobilization were given to him. The cell dose was 4.68 × 10^8MNC/kg. Result： The WBC and PLT were planted respectively on ＋13 d and ＋16 d. DNA fingerprinting results showed engraftement by short tadom repeated-PCR（STR-PCR） on ＋20 d. At the same time, Ph chromosome and Bcr/abl gene were changed into negative. Chronic GVHD（cGVHD） of liver and skin occurred on ＋182 d, and it disappeared gradually without treatment of immunosuppressor. The patient with cytogeneic relapse obtained complete remission（CR） by DLI without mobilization on ＋192 d. The patient with haematological relapse obtained CR by the combination of chemical treatment and DSI with mobilization on ＋192 d. The patient was still alive in disease free state for 567 days after Allo-HSCT and 79 days after DSI. Conclusion：The cell dose of DLI≤0.2 × 10^8MNC/kg was safe and effective for the patients with cytogeneic relapse of CML. The single chemical treatment or DLI was limited for the patient with haematological relapse, and the the combination of chemical treatment and DSI can improve curative effect and avoid of complication.