Nimer S D, Paquette R L, Ireland P, Resta D, Young D, Golde D W
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Exp Hematol. 1994 Aug;22(9):875-80.
We performed a phase I/II study of recombinant human interleukin-3 (rhIL-3) in 21 patients with aplastic anemia (AA) or myelodysplasia (MDS). Patients received 21-day cycles of IL-3 (0.5, 1.25, 2.5, 5.0, or 10 micrograms/kg/d) by subcutaneous injection followed by a 10- to 14-day washout period. Nineteen patients completed at least one 21-day cycle of IL-3. Frequent toxicities of IL-3 included headache, low-grade fever, and erythema at the injection site; at higher doses, weight gain and peripheral edema was seen. Eleven patients developed eosinophilia. Of the 20 evaluable patients, eight had increases in absolute neutrophil counts (seven with MDS, one with AA) including six of the nine patients receiving > or = 5.0 micrograms/kg/d. One AA patient became transfusion-independent for 8 months, while another AA patient had decreased transfusion requirements. Three patients with MDS had at least a doubling of their platelet count, and another patient experienced a 1.9-fold increase. One patient with RAEB progressed to aleukemic AML by the end of one treatment cycle. IL-3 was well-tolerated, but multilineage effects were seen in only 25% of patients with primary bone marrow failure states (five of 20 evaluable) and more commonly in patients with myelodysplastic syndromes. Its optimal use may be as part of combination hematopoietic growth factor therapy.
我们对21例再生障碍性贫血（AA）或骨髓增生异常综合征（MDS）患者进行了重组人白细胞介素-3（rhIL-3）的I/II期研究。患者接受为期21天的IL-3皮下注射疗程（剂量为0.5、1.25、2.5、5.0或10微克/千克/天），随后有10至14天的洗脱期。19例患者完成了至少一个21天的IL-3疗程。IL-3常见的毒性反应包括头痛、低热和注射部位红斑；在较高剂量时，可见体重增加和外周水肿。11例患者出现嗜酸性粒细胞增多。在20例可评估的患者中，8例患者的绝对中性粒细胞计数增加（7例为MDS，1例为AA），其中9例接受≥5.0微克/千克/天的患者中有6例。1例AA患者8个月无需输血，而另1例AA患者输血需求减少。3例MDS患者的血小板计数至少增加了一倍，另1例患者增加了1.9倍。1例RAEB患者在一个治疗周期结束时进展为无白血病的急性髓系白血病（AML）。IL-3耐受性良好，但仅25%的原发性骨髓衰竭患者（20例可评估患者中的5例）出现多系效应，且在骨髓增生异常综合征患者中更常见。其最佳用途可能是作为联合造血生长因子治疗的一部分。
