[使用粒细胞集落刺激因子刺激供体骨髓的单倍体移植的临床研究]

[A clinical study of haploidentical transplantation using granulocyte colony-stimulating factor stimulating donor bone marrow].

作者信息

Chen H, Ji S, Wang H

机构信息

Department of Hematology, General Hospital of Air Force PLA, Beijing 100036, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2001 Nov;40(11):760-3.

PMID:11930684

Abstract

OBJECTIVE

To explore the effects of reducing the incidence of severe acute graft-versus-host disease (GVHD) and improving the disease free survival(DFS) in haploidentical donor transplantation by granlocyte colony-stimulating factor (G-CSF) administration to donor before harvesting and a number of immunosuppresants added to host.

METHODS

Thirteen patients with leukemia received allo-bone marrow transplantation (BMT) from two or three HLA loci mismatched related donor (haploidentical group). The clinical outcomes of the bone marrow transplantion were compared with thase of 13 consecutive HLA identical sibling transplantion (identical group). In haploidentical donor BMT, the donors of patients were given G-CSF (Lenograstim Chugai) 250 micrograms/day for seven doses prior to marrow harvest. CSA, MTX, ATG and mycophenolate mofetil (MMF) were combined for GVHD prophylaxis. ATG 5 mg/kg/day was infused for 4 days before transplantation and MMF was adminisered from 7th day after.

RESULTS

All the patients were engrafted. The median number of CD34+ cells in graft was 6.1 x 10(6)/kg in haploidentical group and 2.5 x 10(6)/kg in identical group (P < 0.01). The median number of CD3+ cells was 50.5 x 10(6)/kg and 47.0 x 10(6)/kg respectively (P > 0.05). All patients had 100% donors hematopoietic cells after transplantation by cytogenetic evidence analysis. Five of the thirteen patients (38.5%) in haploidentical group and three of the thirteen patients(23.1%) in identical group experienced II-IV acute GVHD (P > 0.05). The probability of chronic GVHD was 87.5% in haploidentical group and 67.5% in identical group (P > 0.05), However none in both groups developed extensive cGVHD. The median follow-up duration was 453 days (range 180-690 days) for haploidentical group and 510 days (range 220-810 days) for identical group. In haploidentical group, five patients died from transplant related mortality (3 GVHD, 2 infection), none relapsed and eight patients(61.5%) survive in disease free situation. In identical group, two patients died from transplant related mortality (1 GVHD, 1 infection), two patients died from relapse and nine patients (69.2%) survive in disease free situation. DFS in haploidentical group and in identical group was similar(P > 0.05).

CONCLUSION

The transplants from haploidentical donor used in this study is 3 effective and feasible in preventing acute severe GVHD and improving DFS.

摘要

目的

探讨在单倍体相合供者移植中，于采集前对供者应用粒细胞集落刺激因子（G-CSF）并给受者添加多种免疫抑制剂，对降低严重急性移植物抗宿主病（GVHD）发生率及提高无病生存率（DFS）的影响。

方法

13例白血病患者接受来自两个或三个HLA位点不相合相关供者的异基因骨髓移植（BMT）（单倍体相合组）。将骨髓移植的临床结果与13例连续的HLA全相合同胞移植（全相合组）进行比较。在单倍体相合供者BMT中，患者的供者在骨髓采集前给予G-CSF（利血生，中外制药株式会社）250微克/天，共7剂。联合应用环孢素A（CSA）、甲氨蝶呤（MTX）、抗胸腺细胞球蛋白（ATG）和霉酚酸酯（MMF）预防GVHD。移植前4天给予ATG 5毫克/千克/天，共输注4天，MMF于移植后第7天开始应用。

结果

所有患者均成功植入。单倍体相合组移植物中CD34+细胞中位数为6.1×10⁶/千克，全相合组为2.5×10⁶/千克（P<0.01）。CD3+细胞中位数分别为50.5×10⁶/千克和47.0×10⁶/千克（P>0.05）。通过细胞遗传学证据分析，所有患者移植后供者造血细胞均达100%。单倍体相合组13例患者中有5例（38.5%）、全相合组13例患者中有3例（23.1%）发生Ⅱ-Ⅳ度急性GVHD（P>0.05）。慢性GVHD发生率在单倍体相合组为87.5%，全相合组为67.5%（P>0.05），然而两组均无广泛型慢性GVHD发生。单倍体相合组中位随访时间为453天（范围180-690天），全相合组为510天（范围220-810天）。单倍体相合组中，5例患者死于移植相关死亡率（3例死于GVHD，2例死于感染），无复发，8例患者（61.5%）无病存活。全相合组中，2例患者死于移植相关死亡率（1例死于GVHD，1例死于感染），2例患者死于复发，9例患者（69.2%）无病存活。单倍体相合组和全相合组的DFS相似（P>0.05）。