Crump M, Couture F, Kovacs M, Saragosa R, McCrae J, Brandwein J, Huebsch L, Beauregard-Zollinger L, Keating A
University of Toronto Autologous Bone Marrow Transplant Program, Ontario, Canada.
Exp Hematol. 1993 Mar;21(3):405-410.
Recombinant human interleukin-3 (IL-3) is well-tolerated according to phase I studies, and produces trilineage hematologic responses in patients with normal bone marrow. In addition, promising results have been obtained in a variety of bone marrow failure states. We studied IL-3 in 7 patients with markedly delayed engraftment after autologous bone marrow transplantation (ABMT) for hematologic malignancies (acute myeloid leukemia 4, chronic myeloid leukemia 1, myeloma 1, non-Hodgkin's lymphoma 1). All patients were red blood cell- and platelet transfusion-dependent, had an absolute neutrophil count (ANC) < 0.7 x 10(9)/L and failed to achieve a sustained ANC > 1.0 x 10(9)/L after receiving granulocyte-macrophage colony stimulating factor (GM-CSF) for 28 days. IL-3 was given daily for 21 days at 2 micrograms/kg/d (2 patients) and 5 micrograms/kg/d (5 patients). Toxicity was mild and consisted mostly of low-grade fever and malaise. No changes in platelet, hemoglobin or reticulocyte levels were observed. Four patients had at least a 2-fold increase in ANC at the end of IL-3 treatment. Five patients received GM-CSF 10 micrograms/kg/d subcutaneously for 7 to 10 days immediately after IL-3 and 4 had a further increase in ANC (median 1.7-fold, range 1.6- to 5.8-fold), but no change in platelet transfusion requirements. Hematopoietic colony assays of bone marrow cells obtained before and after treatment showed that granulocyte-macrophage colony-forming cell (CFU-GM) and erythroid blast-forming cell (BFU-E) levels were severely reduced and multilineage progenitors (CFU-GEMM) absent in all patients, and remained low after IL-3 treatment for 21 days. Sequential IL-3 and GM-CSF produced a significant but transient increase in the neutrophil counts of some patients. IL-3 appears to be of limited benefit in patients who are severely aplastic after ABMT and have very low levels of bone marrow progenitors.
根据I期研究结果，重组人白细胞介素-3（IL-3）耐受性良好，可使骨髓正常的患者产生三系血液学反应。此外，在多种骨髓衰竭状态下也取得了有前景的结果。我们对7例血液系统恶性肿瘤（急性髓系白血病4例、慢性髓系白血病1例、骨髓瘤1例、非霍奇金淋巴瘤1例）患者进行自体骨髓移植（ABMT）后植入明显延迟的情况进行了IL-3研究。所有患者均依赖红细胞和血小板输血，绝对中性粒细胞计数（ANC）<0.7×10⁹/L，且在接受粒细胞-巨噬细胞集落刺激因子（GM-CSF）治疗28天后未能实现持续ANC>1.0×10⁹/L。IL-3以2μg/kg/d（2例患者）和5μg/kg/d（5例患者）的剂量每日给药21天。毒性轻微，主要表现为低热和不适。未观察到血小板、血红蛋白或网织红细胞水平的变化。4例患者在IL-3治疗结束时ANC至少增加了2倍。5例患者在IL-3治疗后立即皮下注射GM-CSF 10μg/kg/d，持续7至10天，4例患者的ANC进一步升高（中位数为1.7倍，范围为1.6至5.8倍），但血小板输血需求无变化。治疗前后获得的骨髓细胞造血集落分析显示，所有患者的粒细胞-巨噬细胞集落形成细胞（CFU-GM）和红系爆式集落形成细胞（BFU-E）水平严重降低，多系祖细胞（CFU-GEMM）缺失，且在IL-3治疗21天后仍维持在低水平。序贯使用IL-3和GM-CSF可使部分患者的中性粒细胞计数显著但短暂升高。对于ABMT后严重再生障碍且骨髓祖细胞水平极低的患者，IL-3似乎益处有限。
