Fay J W, Lazarus H, Herzig R, Saez R, Stevens D A, Collins R H, Piñeiro L A, Cooper B W, DiCesare J, Campion M
Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246.
Blood. 1994 Oct 1;84(7):2151-7.
Preclinical studies of recombinant human interleukin-3 (rhIL-3) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) have shown enhancement of multilineage hematopoiesis when administered sequentially. This study was designed to evaluate the safety, tolerability, and biologic effects of sequential administration of rhIL-3 and rhGM-CSF after marrow ablative cytotoxic therapy and autologous bone marrow transplantation (ABMT) for patients with malignant lymphoma. Thirty-seven patients (20 patients with non-Hodgkin's lymphoma and 17 patients with Hodgkin's disease) received one of four different treatment regimens before ABMT. Patients were entered in one of four study groups to receive rhIL-3 (2.5 or 5.0 micrograms/kg/day) administered by subcutaneous injection for either 5 or 10 days starting 4 hours after the marrow infusion. Twenty-four hours after the last dose of rhIL-3, rhGM-CSF (250 micrograms/m2/d as a 2-hour intravenous infusion) administration was initiated. rhGM-CSF was administered daily until the absolute neutrophil count (ANC) was > or = 1,500/microL for 3 consecutive days or until day 27 posttransplant. The most frequent adverse events in the trial included nausea, fever, diarrhea, mucositis, vomiting, rash, edema, chills, abdominal pain, and tachycardia. Three patients were removed from the study because of chest, skeletal, and abdominal pain felt to be probably related to study drug. Four patients died during the study period because of complications unrelated to either rhIL-3 or rhGM-CSF. The median time to recovery of neutrophils (ANC > or = 500/microL) and platelets (platelet count > or = 20,000/microL) was 14 and 15 days, respectively. There were fewer days of platelet transfusions than seen in historical control groups using rhGM-CSF, rhG-CSF, or rhIL-3 alone. In addition, there were fewer days of red blood cell transfusions compared with historical controls using no cytokines or rhGM-CSF. These data indicate that the sequential administration of rhIL-3 and rhGM-CSF after ABMT is safe and generally well-tolerated and results in rapid recovery of multilineage hematopoiesis.
重组人白细胞介素-3（rhIL-3）和粒细胞-巨噬细胞集落刺激因子（rhGM-CSF）的临床前研究表明，序贯给药时可增强多系造血功能。本研究旨在评估恶性淋巴瘤患者在进行骨髓清除性细胞毒性治疗和自体骨髓移植（ABMT）后序贯给予rhIL-3和rhGM-CSF的安全性、耐受性及生物学效应。37例患者（20例非霍奇金淋巴瘤患者和17例霍奇金病患者）在ABMT前接受了四种不同治疗方案中的一种。患者被纳入四个研究组之一，在骨髓输注后4小时开始皮下注射rhIL-3（2.5或5.0微克/千克/天），持续5天或10天。在最后一剂rhIL-3给药24小时后，开始静脉输注rhGM-CSF（250微克/平方米/天，持续2小时）。每日给予rhGM-CSF，直至绝对中性粒细胞计数（ANC）连续3天≥1500/微升或直至移植后第27天。试验中最常见的不良事件包括恶心、发热、腹泻、粘膜炎、呕吐、皮疹、水肿、寒战、腹痛和心动过速。3例患者因感觉可能与研究药物有关的胸部、骨骼和腹痛而退出研究。4例患者在研究期间因与rhIL-3或rhGM-CSF无关的并发症死亡。中性粒细胞（ANC≥500/微升）和血小板（血小板计数≥20000/微升）恢复的中位时间分别为14天和15天。与单独使用rhGM-CSF、rhG-CSF或rhIL-3的历史对照组相比，血小板输注天数更少。此外，与未使用细胞因子或rhGM-CSF的历史对照组相比，红细胞输注天数更少。这些数据表明，ABMT后序贯给予rhIL-3和rhGM-CSF是安全的，且一般耐受性良好，并能使多系造血功能快速恢复。
