[异基因外周血干细胞移植治疗白血病的移植物抗宿主病研究]

[Study on graft-versus-host disease in the allogeneic peripheral blood stem cell transplantation for the treatment of leukemia].

作者信息

Zhang Wei-ping, Wang Jian-min, Ju Xiao-ping, Song Xian-min, Tong Shu-peng, Li Hong-mei

机构信息

Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2003 Mar;24(3):129-33.

PMID:12697123

Abstract

OBJECTIVE

To analyze the incidence and the effective prevention and treatment of graft-versus-host disease (GVHD) for the allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for the treatment of leukemia.

METHODS

Fifty patients with acute leukemia (n = 29) and chronic myeloid leukemia (n = 21) were treated with allo-PBSCT. The conditioning regimens were TBI plus CTX and Vp16 or TBI plus CTX. Two regimens were used for prophylaxis of GVHD: one was the combination of low dose cyclosporine (CsA, 2 - 3 mg x kg(-1) x d(-)1 i.v. or 4 - 6 mg x kg(-1) x d(-1) p.o.) and short course methotrexate (MTX, 15 approximately 10 mg, +1, +3, +6, +11 d) (CsA/MTX group, 32 patients), the other was short course of mycophenolate mofetil (MMF, 1.0 bid, +1 - +28 d) in addition to CsA and MTX (MMF/CsA/MTX group, 18 patients).

RESULTS

All patients were successfully engrafted and the median times to ANC > 0.5 x 10(9)/L and to platelet > 20 x 10(9)/L were 14 (10 - 22) and 20 (10 - 68) days post PBSCT respectively. The incidence of acute GVHD (aGVHD) was 40% (20/50) and of grade III - IV was 12% (6/50). The chronic GVHD (cGVHD) occurred in 22 out of 33 (66.7%) evaluable patients (survived longer than 6 months post PBSCT) and extensive cGVHD in 11 out of 33 (33.3%) patients. Patients with aGVHD displayed significantly higher sIL-2R levels [(277.3 +/- 26.4) U/L] and CD(25)(+) cells [(8.1 +/- 3.4)%] than those without GVHD [(128.1 +/- 96.7) U/L and (3.6 +/- 1.7)%] (P < 0.05). The incidences of aGVHD (16.7%) and extensive cGVHD (9.1%) in MMF/CsA/MTX group were significantly lower than that in CsA/MTX group (53.1% and 45.5%, P < 0.05). The median follow-up duration was 30 (3 - 70) months and 33 patients were still alive. The relapse rate was significantly higher in GVHD negative group (47.1%) than in GVHD positive group (0, P < 0.05). The 3 year disease-free-survival (DFS) rate was 66%.

CONCLUSION

The incidence of aGVHD was low, but of cGVHD was high in allo-PBSCT. sIL-2R and CD(25)(+) cells after PBSCT may provide predictive markers for aGVHD. The MMF/CsA/MTX regimen for prevention of aGVHD in allo-PBSCT is more effective than the CsA/MTX one. There was a strong antileukemic effect of GVHD in the allo-PBSCT.

摘要

目的

分析异基因外周血干细胞移植（allo-PBSCT）治疗白血病时移植物抗宿主病（GVHD）的发生率及有效的防治措施。

方法

50例急性白血病患者（n = 29）和慢性髓性白血病患者（n = 21）接受allo-PBSCT治疗。预处理方案为全身照射（TBI）加环磷酰胺（CTX）和依托泊苷（Vp16）或TBI加CTX。采用两种方案预防GVHD：一种是低剂量环孢素（CsA，静脉注射2 - 3mg·kg⁻¹·d⁻¹或口服4 - 6mg·kg⁻¹·d⁻¹）与短疗程甲氨蝶呤（MTX，15约10mg，+1、+3、+6、+11天）联合应用（CsA/MTX组，32例患者），另一种是在CsA和MTX基础上联合短疗程霉酚酸酯（MMF，1.0 bid，+1 - +28天）（MMF/CsA/MTX组，18例患者）。

结果

所有患者均成功植入，移植后中性粒细胞绝对值（ANC）>0.5×10⁹/L和血小板>20×10⁹/L的中位时间分别为14（10 - 22）天和20（10 - 68）天。急性GVHD（aGVHD）发生率为40%（20/50），Ⅲ - Ⅳ级为12%（6/50）。33例可评估患者（移植后存活超过6个月）中有22例发生慢性GVHD（cGVHD），33例患者中有11例发生广泛cGVHD。发生aGVHD的患者血清白细胞介素-2受体（sIL-2R）水平[（277.3±26.4）U/L]和CD25⁺细胞[（8.1±3.4）%]显著高于未发生GVHD的患者[（128.1±96.7）U/L和（3.6±1.7）%]（P < 0.05）。MMF/CsA/MTX组aGVHD发生率（16.7%）和广泛cGVHD发生率（9.1%）显著低于CsA/MTX组（53.1%和45.5%，P < 0.05））。中位随访时间为30（3 - 70）个月，33例患者仍存活。GVHD阴性组复发率（47.1%）显著高于GVHD阳性组（0，P < 0.05）。3年无病生存率（DFS）为66%。