非清髓性异基因造血干细胞移植联合供者淋巴细胞输注治疗恶性血液病

目的：探讨非清髓性异基因造血干细胞移植（non-myeloablative allogeneic stem cell transplantation，NAST）联合供者淋巴细胞输注（DLI）治疗恶性血液病的疗效和并发症。方法：采用FBCA方案氟达拉宾30mg／（m^2·d），用5d；马利兰4mg（kg·d），用2d；环磷酰胺0．6～0．8g／d，用2天；Ara-C2g/（m^2·d），用5d]对12例恶性血液病患者预处理，行异基因造血干细胞移植，移植后第30d开始予DLI，并动态观察造血恢复指标、嵌合状态、GVHD及疗效指标。结果：12例患者造血顺利恢复，中性粒细胞（ANC）〉0．5×10^9／L平均为13d，血小板计数（PLT）〉20×10^9／L平均为14．5d，移植后第30d时经短串重复系列（STR—PCR）检测12例植活患者中10例为完全嵌合状态（CDC），2例为混合嵌合体，第90d时又有1例患者转为CDC，发生Ⅲ～Ⅳ度急性GVHD3例（25％），Ⅱ度急性GVHD1例（8．3％），发生慢性GVHD5例（41．7％），死亡3例，2例死于移植相关合并症，1例死于复发，9例存活，中位随访时间为321d（75～1143d），3例持续CR，2年总生存率、无病生存率及复发率分别为66．7％、58．3％及8．3％。结论：NAST联合DLI治疗恶性血液病安全可靠，造血功能恢复迅速且持久稳定，长期无病生存率高，急性GVHD发病率、严重程度低，而白血病复发率并未增加。

Non-myeloablative allogeneic stem cell transplantation in combination with donor lymphocyte infusion for malignant hematologic disease

Objective：To explore the efficacy and complications of non-myeloablative allogeneic stem cell transplantation （NAST） in combination with donor lymphocyte infusion（DLI） for malignant hematologic disease. Methods：Twelve patients with ma- lignant hematologic diseases received NAST of which the conditioning regimen was consisted of fludarabine 30mg/（ cm2 · d ） , 5d ], busulfan4mg/（kg-d） , ,2d] , cyclophosphamide（0. 6-0. 8g/d,2d） and Ara-C（ lg/m^2 q12h,5d）. All patients received donor lympho- cyte infusion on day 28-35 after transplantation. Hematopoietic reconstitution, chimera, graft versus host disease （GVHD） and effect of therapy were observed. Results.All of 12 patients received NAST were acquired rehematopoietic reconstitution successfully, The median days of granulocyte 〉 0. 5 ×10^9/L and platelet 〉 20× 10^9/L were 13 days （range 10-16） and 14. 5 days （ range 12-22）, espectively. Ten patients acquired the form of donor hematopoietic cells complete chimera and 2 patients acquired the form of donor-receipients hematopoietic cells mixed chimera on day 30 after transplantation. 1 patient was converted gradually into complete chimera on day 90 after transplantation. Grade Ⅲ-Ⅳ Acute GVI-ID occurred in 3 of 12 patients（25% ） , grade U aGVHD occurred in 1 of 12 patients （8.3%）. Chronic GVHDs were seen in 5 of 12 evaluable patients （41.7%）. Three patients died, including 2 of transplant related complications, 1 of relapse. Nine patients were alive with a median follow-up duration of 321 （75-1 143 ） days, and among them 3 patients were in continuous complete remission. The 2-year probability of overall survival disease-free survival（DFS） and relapsed was 66.7%, 58.3% and 8.3% , respectively. Condusion：NAST in combination with DLI was safe and effective for the treatment of malignant hematologic disease, hematopoietic reconstitution was rapid and stable, the probability of long disease free surival was high, GVHD was low in incidence and little in