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氟达拉滨和阿糖胞苷联合化疗后输注供体血干细胞治疗异基因造血干细胞移植后急性白血病复发

Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation.

作者信息

You Yong, Li Qiu-bai, Chen Zhi-chao, Li Wei-ming, Xia Ling-hui, Zhou Hao, Zou Ping

机构信息

Institute of Haematology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Chin Med J (Engl). 2008 Sep 20;121(18):1770-4.

PMID:19080355
Abstract

BACKGROUND

Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after allo-HSCT.

METHODS

Seven patients, median age 34 years, with relapse of acute leukaemia after allo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range, 38 - 185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered.

RESULTS

Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value = 0.5 x 10(9)/L and for platelet value = 20 x 10(9)/L were 13 days (range, 10 - 18 days) and 15 days (range, 11 - 24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively.

CONCLUSIONS

Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after allo-HSCT. The disease free state of patients may increase, though with high risk of secondary fungal infection.

摘要

背景

复发仍然是急性白血病患者异基因造血干细胞移植(allo-HSCT)成功的障碍,且尚无标准治疗方法。我们评估了氟达拉滨和阿糖胞苷联合输注供体造血干细胞治疗allo-HSCT后急性白血病复发的疗效。

方法

7例allo-HSCT后急性白血病复发的患者,中位年龄34岁,接受了氟达拉滨与阿糖胞苷联合化疗5天。5例为急性髓系白血病(2例难治性),2例为难治性急性淋巴细胞白血病。移植后,中位复发时间为110天(范围38 - 185天)。化疗2天后,5例患者接受了经粒细胞集落刺激因子动员的供体外周血干细胞输注。未给予移植物抗宿主病预防性药物。

结果

6例患者实现造血重建。治疗后第30天的DNA序列分析显示均为完全供体嵌合型。中位观察时间为189天。治疗后,中性粒细胞值=0.5×10⁹/L和血小板值=20×10⁹/L的中位时间分别为13天(范围10 - 18天)和15天(范围11 - 24天)。2例患者发生急性移植物抗宿主病,3例发生慢性移植物抗宿主病。5例患者发生肺部真菌感染(2例死亡),3例出血性膀胱炎,2例巨细胞病毒血症。其他患者死于白血病相关死亡。3例接受供体外周血干细胞再输注的慢性移植物抗宿主病患者分别存活了375天、232天和195天。

结论

氟达拉滨联合阿糖胞苷加供体造血干细胞应被视为allo-HSCT后急性白血病复发的有效治疗方案。患者的无病状态可能会增加,尽管继发真菌感染风险较高。

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