Guinan E C, Lopez K D, Huhn R D, Felser J M, Nathan D G
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts.
J Pediatr. 1994 Jan;124(1):144-50. doi: 10.1016/s0022-3476(94)70271-3.
Fanconi anemia is a congenital syndrome characterized by multiple specific physical anomalies, progressive marrow failure, and a predisposition to acute leukemia. We studied the toxicity and efficacy of daily subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with Fanconi anemia and pancytopenia. The toxicity of GM-CSF at the doses and schedule used was minimal. Six of seven patients entered had an increase in the neutrophil count of 7- to 25-fold, which was maintained during the course of study. Despite increases in the reticulocyte count, increases in hemoglobin concentration were rare. No improvement in platelet count was evident in any patient. No patient has evidence of leukemia after up to 19 months of continuous GM-CSF exposure, and all five surviving patients remain responsive to treatment. Although the optimal dose, schedule, and choice of cytokine for patients with marrow failure and Fanconi anemia are not established by this preliminary study, the data indicate that (1) GM-CSF may be able to palliate at least the neutropenia and potentially the neutropenic complications of the disease, (2) this effect can be sustained for more than 1 year, and (3) rapid evolution of acute leukemia is unlikely to be a frequent outcome of such treatment. The clinical impact of GM-CSF or other cytokines in patients with Fanconi anemia and pancytopenia remains to be established by further studies.
范可尼贫血是一种先天性综合征，其特征为多种特定的身体异常、进行性骨髓衰竭以及易患急性白血病。我们研究了每日皮下注射重组人粒细胞-巨噬细胞集落刺激因子（GM-CSF）对范可尼贫血和全血细胞减少症患者的毒性和疗效。所用剂量和给药方案的GM-CSF毒性极小。入组的7名患者中有6名中性粒细胞计数增加了7至25倍，且在研究过程中一直维持。尽管网织红细胞计数增加，但血红蛋白浓度升高的情况很少见。任何患者的血小板计数均无明显改善。在连续接受GM-CSF治疗长达19个月后，没有患者出现白血病迹象，所有5名存活患者对治疗仍有反应。尽管这项初步研究尚未确定骨髓衰竭和范可尼贫血患者的最佳剂量、给药方案和细胞因子选择，但数据表明：（1）GM-CSF可能至少能够缓解该疾病的中性粒细胞减少症以及潜在的中性粒细胞减少并发症；（2）这种效果可持续1年以上；（3）急性白血病的快速进展不太可能是此类治疗的常见结果。GM-CSF或其他细胞因子对范可尼贫血和全血细胞减少症患者的临床影响仍有待进一步研究确定。
