Meyers J D, Flournoy N, Sanders J E, McGuffin R W, Newton B A, Fisher L D, Lum L G, Appelbaum F R, Doney K, Sullivan K M
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Ann Intern Med. 1987 Dec;107(6):809-16. doi: 10.7326/0003-4819-107-6-809.
To determine the efficacy of prophylactic interferon for prevention of cytomegalovirus infection and relapse of leukemia after allogeneic marrow transplantation.
Randomized trial with intermittent interferon administration to day 80 after transplantation.
Marrow transplantation units of a cancer research center.
Consecutive patients with acute lymphocytic leukemia in remission at the time of transplantation. Thirty-nine patients received interferon, and 40 were control patients.
Partially purified human leukocyte interferon given every 3 days beginning after marrow engraftment and continuing to day 80 after transplantation. After initial safety testing, the starting and minimum dose was 6 X 10(4) units/kg of body weight, with dose escalations determined by the circulating neutrophil count. Transplant conditioning and post-transplantation prophylaxis of graft-versus-host disease with methotrexate followed standard procedures.
No difference was observed in the probability or severity of cytomegalovirus infection or in the probability or severity of graft-versus-host disease. Relapse of leukemia occurred in 9 interferon recipients and 21 control patients, with a minimum follow-up of 4 years among surviving patients. The probability of relapse among all interferon recipients was 0.36 (95% confidence interval [Cl], 0.56 to 0.17) and among all control patients was 0.74 (95% Cl, 0.91 to 0.58) (p = 0.04 by log-rank test). Among patients who received transplants in first or second remission, the probability of relapse among interferon recipients was 0.19 (95% Cl, 0.37 to 0.02) compared with 0.71 (95% Cl, 0.97 to 0.51) among control patients (p = 0.008 by log-rank test). Survival rates did not differ between interferon recipients and control patients. Transient decreases in leukocyte count and anorexia and nausea occurred among interferon recipients. Six interferon recipients, all of whom had received chemoradiotherapy of the central nervous system before transplantation, developed leukoencephalopathy after transplantation.
These data suggest that interferon given after transplantation reduces the risk for subsequent relapse of leukemia. The effect of longer administration and of administration in patients with other underlying diseases will require additional trials. No effect was observed on cytomegalovirus infection, either because interferon was not initiated until a median of 18 days after transplantation or because of a lesser effect among marrow allograft recipients.
确定预防性使用干扰素预防异基因骨髓移植后巨细胞病毒感染及白血病复发的疗效。
移植后第80天进行间歇性干扰素给药的随机试验。
癌症研究中心的骨髓移植单元。
移植时处于缓解期的急性淋巴细胞白血病连续患者。39例患者接受干扰素治疗，40例为对照患者。
从骨髓植入后开始，每3天给予部分纯化的人白细胞干扰素，持续至移植后第80天。经过初始安全性测试后，起始剂量和最低剂量为6×10⁴单位/千克体重，剂量递增根据循环中性粒细胞计数确定。移植预处理及移植后用甲氨蝶呤预防移植物抗宿主病遵循标准程序。
在巨细胞病毒感染的发生率或严重程度以及移植物抗宿主病的发生率或严重程度方面未观察到差异。9例接受干扰素治疗的患者和21例对照患者出现白血病复发，存活患者的最短随访时间为4年。所有接受干扰素治疗患者的复发概率为0.36（95%置信区间[CI]，0.56至0.17），所有对照患者的复发概率为0.74（95%CI，0.91至0.58）（对数秩检验，p = 0.04）。在首次或第二次缓解期接受移植的患者中，接受干扰素治疗患者的复发概率为0.19（95%CI，0.37至0.02），而对照患者为0.71（95%CI，0.97至0.51）（对数秩检验，p = 0.008）。接受干扰素治疗患者和对照患者的生存率无差异。接受干扰素治疗的患者出现白细胞计数短暂下降、厌食和恶心。6例接受干扰素治疗的患者在移植后发生白质脑病，他们在移植前均接受过中枢神经系统的放化疗。
这些数据表明移植后给予干扰素可降低白血病后续复发的风险。延长给药时间以及在其他基础疾病患者中给药的效果需要进一步试验。未观察到对巨细胞病毒感染有影响，这要么是因为直到移植后中位数18天才开始使用干扰素，要么是因为在骨髓同种异体移植受者中的效果较差。
