Rutella S, Pierelli L, Sica S, Serafini R, Chiusolo P, Paladini U, Leone F, Zini G, D'Onofrio G, Leone G, Piccirillo N
Department of Hematology Catholic University Medical School Rome, Rome, Italy.
Cytotherapy. 2003;5(1):19-30. doi: 10.1080/14653240310000047.
The transfusion of G-CSf-primed granulocytes (GTX) might represent an important treatment option for neutropenia-related infections unresponsive to conventional antimicrobial therapies and to recombinant hematopoietic growth factors. However, few studies to date have identified the factors that can predict clinical outcome and the patient populations who are likely to benefit most from GTX. The primary endpoint of the present retrospective study was to evaluate the efficacy of GTX in 22 patients with hematological malignancies who developed neutropenia-related bacterial and fungal infections that were unresponsive to appropriate antimicrobial therapies.
Peripheral blood granulocytes were collected by continuous-flow leukapheresis from HLA-identical siblings after priming with G-CSF. The response to GTX was classified as 'favorable' if clinical symptoms and signs of infection resolved or 'unfavorable' if clinical symptoms and signs of infection were unchanged or worsened. Control of infection at Day 30 after the enrollment in the GTX program was considered as the outcome variable in multiple regression analysis.
Two patients died of infection before receiving the granulocyte concentrates. Bacterial infections (monomicrobial or mixed bacteremias) were documented in 11 patients, whereas fungal infections (fungemia or focal fungal infections) were diagnosed in seven patients. In two patients, no infecting agent could be isolated (clinical infection). Control of infection at Day 30 after the first GTX was achieved in 10 of 20 assemble patients. Overall, 54% of patients with bacterial infections had a favorable response, compared with 57% of patients with fungal infections. No differences in terms of survival were found when comparing patients with bacterial and those with fungal infections at a median follow-up 90 days from the first GTX. In univariate analysis, disease status before GTX, e.g., complete or partial remission, and spontaneous recovery of the neutrophil count were significantly associated with control of infection. when multivariate regression models were formed, the recovery 0.5 x 10 (9)/L PMN was the only parameter that significantly and independently correlated with a favorable response to GTX.
GTX can be used to successfully treat bacterial as well as fungal infections in severely neutropenic patients when administered early after the onset of febrile neutropenia in patients with remission of the underlying disease and who are likely to recover marrow function.
对于对传统抗菌疗法和重组造血生长因子无反应的中性粒细胞减少相关感染，输注经粒细胞集落刺激因子（G-CSF）预处理的粒细胞（GTX）可能是一种重要的治疗选择。然而，迄今为止，很少有研究确定能够预测临床结局的因素以及可能从GTX中获益最大的患者群体。本回顾性研究的主要终点是评估GTX对22例血液系统恶性肿瘤患者的疗效，这些患者发生了对适当抗菌治疗无反应的中性粒细胞减少相关细菌和真菌感染。
在经G-CSF预处理后，通过连续流式白细胞分离术从HLA相同的同胞中采集外周血粒细胞。如果感染的临床症状和体征消失，则将对GTX的反应分类为“良好”；如果感染的临床症状和体征未改变或恶化，则分类为“不良”。在GTX治疗方案入组后第30天的感染控制情况被视为多元回归分析中的结果变量。
两名患者在接受粒细胞浓缩物之前死于感染。11例患者记录有细菌感染（单一微生物或混合菌血症），而7例患者诊断为真菌感染（真菌血症或局灶性真菌感染）。两名患者中未分离出感染病原体（临床感染）。在20例接受治疗的患者中，有10例在首次输注GTX后第30天实现了感染控制。总体而言，54%的细菌感染患者反应良好，而真菌感染患者的这一比例为57%。在从首次输注GTX开始的中位随访90天时，比较细菌感染患者和真菌感染患者时，未发现生存差异。在单变量分析中，GTX治疗前的疾病状态，例如完全或部分缓解，以及中性粒细胞计数的自发恢复与感染控制显著相关。当形成多元回归模型时，PMN恢复至0.5×10⁹/L是唯一与对GTX的良好反应显著且独立相关的参数。
对于基础疾病缓解且可能恢复骨髓功能的患者，在发热性中性粒细胞减少症发作后早期给予GTX，可成功治疗严重中性粒细胞减少患者的细菌和真菌感染。
