人白细胞抗原相合同胞骨髓移植后糖基化重组人粒细胞集落刺激因子的II期研究

Phase II study of glycosylated recombinant human granulocyte colony-stimulating factor after HLA-identical sibling bone marrow transplantation.

作者信息

Lickliter J D, Roberts A W, Grigg A P

机构信息

Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Melbourne, Vic.

出版信息

Aust N Z J Med. 1994 Oct;24(5):541-6. doi: 10.1111/j.1445-5994.1994.tb01755.x.

DOI:10.1111/j.1445-5994.1994.tb01755.x

PMID:7531433

Abstract

BACKGROUND

The lengthy period of neutropenia which follows allogeneic bone marrow transplantation (BMT) results in significant morbidity and some mortality. Recombinant human granulocyte colony-stimulating factor (rhuG-CSF) effectively reduces neutropenia and morbidity when given after autologous BMT, but has not been adequately investigated in allografts.

AIMS

To assess the tolerability, safety and efficacy of rhuG-CSF after allogeneic BMT.

METHODS

rhuG-CSF was administered to 13 adult patients with haematological malignancies after HLA-identical sibling BMT. Five micrograms/kg of rhuG-CSF was given daily by subcutaneous bolus injection, commencing four hours after marrow infusion and continuing until the neutrophil count was > or = 1.0 x 10(9)/L on three consecutive days. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin and short-course methotrexate (days 1, 3, 6 and 11). Prophylactic intravenous (IV) antibiotics were administered from the onset of neutropenia. The control group consisted of patients with comparable diagnoses, transplanted before and after the current study using identical supportive care and GVHD prophylaxis policies.

RESULTS

Although time to recovery of the neutrophil count to > 0.1 x 10(9)/L was similar, the rhuG-CSF-treated patients experienced accelerated recovery to > 0.5 x 10(9)/L, which occurred at a median of 15 days (range 11-21) after marrow infusion in study patients compared to 18.5 days (range 14-41) in the controls (p = 0.04). No significant differences were detected in any of the indices of transplant-related morbidity examined, including the number of days of fever, the incidence of culture-positive infections, the usage of antibiotics, the requirement for parenteral nutrition and IV morphine, the maximum severity of mucositis and GVHD, and the day of discharge.

CONCLUSION

Within the context of this study, rhuG-CSF had limited impact on the clinical outcome of HLA-identical sibling BMT.

摘要

背景

异基因骨髓移植（BMT）后会出现长时间的中性粒细胞减少，导致显著的发病率和一定的死亡率。重组人粒细胞集落刺激因子（rhuG-CSF）在自体BMT后使用时可有效减轻中性粒细胞减少和发病率，但在异基因移植中的研究尚不充分。

目的

评估异基因BMT后rhuG-CSF的耐受性、安全性和疗效。

方法

对13例血液系统恶性肿瘤成年患者在接受HLA相合同胞BMT后给予rhuG-CSF。rhuG-CSF剂量为5微克/千克，每天皮下推注，在骨髓输注后4小时开始，持续至中性粒细胞计数连续3天≥1.0×10⁹/L。移植物抗宿主病（GVHD）预防采用环孢素和短疗程甲氨蝶呤（第1、3、6和11天）。从中性粒细胞减少开始即给予预防性静脉抗生素。对照组由诊断相似的患者组成，在本研究之前和之后进行移植，采用相同的支持治疗和GVHD预防方案。

结果

尽管中性粒细胞计数恢复至>0.1×10⁹/L的时间相似，但接受rhuG-CSF治疗的患者恢复至>0.5×10⁹/L的速度加快，研究组患者在骨髓输注后中位时间为15天（范围11 - 21天），而对照组为18.5天（范围14 - 41天）（p = 0.04）。在检查的任何移植相关发病率指标中均未发现显著差异，包括发热天数、培养阳性感染发生率、抗生素使用情况、胃肠外营养和静脉注射吗啡的需求、粘膜炎和GVHD的最大严重程度以及出院日期。