Turgeon N, Hovingh G K, Fishman J A, Basgoz N, Tolkoff-Rubin N E, Doran M, Cosimi A B, Rubin R H
Transplantation Unit, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA.
Transpl Infect Dis. 2000 Mar;2(1):15-21. doi: 10.1034/j.1399-3062.2000.020104.x.
Leukopenia is not infrequently encountered following solid organ transplantation, most often in the setting of cytomegalovirus (CMV) disease and/or its treatment with ganciclovir. The present study was undertaken to determine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) in renal and liver transplant recipients with leukopenia.
Between 1 June 1991 and 1 June 1998, patients received G-CSF for 2 indications: 1) white blood cell count (WBC) < 3000/mm3, with a decline from baseline; 2) to shorten the duration of leukopenia associated with chemotherapy. A retrospective review of the outcome of such therapy was undertaken.
50 patients were given 100 courses of treatment with G-CSF; 35 of 168 liver transplant recipients (20.8%), 14 of 391 kidney transplant recipients (3.6%), and 1 of 4 recipients of combined liver-kidney transplants (25.0%) received from 1 to 9 courses of G-CSF. Presumed causes of leukopenia were identified as ganciclovir in 28 cases (28.0%), CMV in 21 (21.0%), chemotherapy in 12 (12.0%), sepsis in 11 (11.0%), azathioprine in 5 (5.0%), interferon in 3 (3.0%) and other causes in 20 cases (20.0%). The median length of therapy was 10.0 days (range 1-154 days) and the average dose of daily G-CSF received was 3.9+/-1.5 microg/kg/day. The average WBC was (2.4+/-1.3 )x 10(3)/microl at the beginning of therapy, and (13.8+/-9.1) x 10(3)/microl at the end of therapy. In 7 of 100 treatments (7.0%) a WBC of 5.0 x 10(3)/microl was not reached during G-CSF therapy; in 6 of these 7 cases, G-CSF therapy lasted fewer than 4 days. The mean time needed to reach a WBC count of 5 x 10(3)/microl was 3.7+/-3.3 days among 71 patients who had daily WBC counts sent. Eight G-CSF treatments (8.0%) were followed by episodes of rejection appearing during or within 2 months of treatment; 5 of them were biopsy-documented. No relation was found between the highest WBC obtained during G-CSF therapy and the risk of rejection. Eight patients (16.0%) died while receiving G-CSF, all from infection. Six of these 8 patients were receiving G-CSF for leukopenia secondary to sepsis. Overall, 25 patients (50.0%) received 49 courses of G-CSF secondary to CMV and/or ganciclovir therapy. In 40 of 49 courses (81.6%), ganciclovir could be continued at recommended doses. Twenty-one of 22 patients (95.5%) with symptomatic CMV infection had a clinical response to ganciclovir. Sixteen of 18 patients (88.9%) treated for a CMV infection and followed with serial antigenemia assays attained microbiological cure; both patients who did not were infected with ganciclovir resistant CMV.
G-CSF was well tolerated in solid organ transplant recipients. It was particularly useful in patients with CMV disease, allowing optimal ganciclovir therapy.
实体器官移植后白细胞减少症并不少见，最常见于巨细胞病毒（CMV）疾病和/或用更昔洛韦治疗的情况下。本研究旨在确定粒细胞集落刺激因子（G-CSF）在肾和肝移植受者白细胞减少症中的安全性和有效性。
在1991年6月1日至1998年6月1日期间，患者因2种指征接受G-CSF治疗：1）白细胞计数（WBC）<3000/mm3，且较基线水平下降；2）缩短与化疗相关的白细胞减少持续时间。对该治疗结果进行回顾性分析。
50例患者接受了100疗程的G-CSF治疗；168例肝移植受者中的35例（20.8%）、391例肾移植受者中的14例（3.6%）以及4例肝肾联合移植受者中的1例（25.0%）接受了1至9疗程的G-CSF治疗。白细胞减少的推测原因在28例（28.0%）中被确定为更昔洛韦，21例（21.0%）为CMV，12例（12.0%）为化疗，11例（11.0%）为败血症，5例（5.0%）为硫唑嘌呤，3例（3.0%）为干扰素，20例（20.0%）为其他原因。治疗的中位时长为10.0天（范围1 - 154天），每日接受的G-CSF平均剂量为3.9±1.5μg/kg/天。治疗开始时平均白细胞计数为（2.4±1.3）×10³/μl，治疗结束时为（13.8±9.1）×10³/μl。在100次治疗中有7次（7.0%）在G-CSF治疗期间未达到白细胞计数5.0×10³/μl；在这7例中的6例中，G-CSF治疗持续少于4天。在71例每日进行白细胞计数的患者中，达到白细胞计数5×10³/μl所需的平均时间为3.7±3.3天。8次G-CSF治疗（8.0%）之后在治疗期间或治疗后2个月内出现排斥反应；其中5次有活检记录。在G-CSF治疗期间获得的最高白细胞计数与排斥风险之间未发现关联。8例患者（16.0%）在接受G-CSF治疗时死亡，均死于感染。这8例患者中有6例因败血症继发白细胞减少而接受G-CSF治疗。总体而言，25例患者（50.0%）因CMV和/或更昔洛韦治疗继发接受了49疗程的G-CSF治疗。在49疗程中的40例（81.6%）中，更昔洛韦可按推荐剂量继续使用。22例有症状CMV感染的患者中有21例（95.5%）对更昔洛韦有临床反应。18例接受CMV感染治疗并进行系列抗原血症检测随访的患者中有16例（88.9%）实现了微生物学治愈；未治愈的2例患者感染的是对更昔洛韦耐药的CMV。
G-CSF在实体器官移植受者中耐受性良好。它在CMV疾病患者中特别有用，可使更昔洛韦治疗达到最佳效果。
