ALTERNATING 2'-DCF AND RECOMBINANT LEUKOCYTE A IFN IN HAIRY CELL LEUKEMIA

交替 2-DCF 和重组白细胞 A 干扰素治疗毛细胞白血病

• 批准号: 3838193
• 负责人: J W SMITH
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838193
• 关键词: antileukemic agent; biopsy; blood cell count; bone marrow exam; clinical trials; combination chemotherapy; deoxyadenosines; deoxycoformycin; drug adverse effect; hairy cell leukemia; human subject; human therapy evaluation; human tissue; interferons; longitudinal human study; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer remission /regression; recombinant DNA

We administered deoxycoformycin (dCF) and interferon-alfa (IFN-alpha) sequentially to patients with hairy cell leukemia in an attempt to improve the response rate and duration observed in earlier studies using each drug alone. Further rationale for this study included the observation that IFN-alpha resistant patients were nearly uniformally responsive to second line dCF. As there was some overlapping toxicity, we decided to administer the drugs sequentially rather than concurrently. In this study, we evaluated patients for response by performing bilateral iliac crest bone marrow biopsies and aspirates since the peripheral blood normalizes rapidly after either IFN-alpha or dCF treatment but disease becomes patchy in the bone marrow and might be missed if only unilateral bone marrow biopsies had been performed. Other studies using IFN-alpha or dCF alone used unilateral marrow examinations in evaluating response. Using these more relaxed criteria of response, authors had published high rates of complete remission to dCF. Of 15 patients entered in our study, 14 are evaluable for response with one patient having diffuse osteosclerosis not being evaluable for marrow response. All patients had rapid normalization of peripheral blood counts and all 14 marrow-evaluable patients were found to have very small numbers (less than 5% of the total marrow cellularity) of residual hairy cells at the completion of treatment. Among the 14 evaluable patients, only one patient developed progressive disease off treatment. The single nonevaluable patient with diffuse osteosclerosis developed anemia with increasing serum soluble IL-2 receptor levels consistent with progressive hairy cell leukemia. These patients are receiving treatment with 2-chlorodeoxyadenosine and interferon-alfa, respectively. Although the initial response rate to the combination of dCF and interferon appears to be no better than that observed with dCF alone, the response duration may be longer. The remaining patients continue to be followed for determination of response duration.

我们管理脱氧霉素（DCF）和干扰素-Alfa（IFN-Alpha） 依次与毛细胞白血病患者进行 提高使用先前研究中观察到的响应率和持续时间 每种药物。 这项研究的进一步理由包括 观察到IFN-Alpha耐药患者几乎均匀 响应第二行DCF。 由于有一些重叠的毒性， 我们决定依次而不是同时管理药物。 在这项研究中，我们通过进行双边评估了患者的反应 伊利亚克峰骨髓活检和抽吸物以来是外周血 IFN-Alpha或DCF治疗后迅速归一化，但疾病 在骨髓中变斑 已经进行了骨髓活检。 其他使用IFN-alpha的研究 或单独使用DCF使用单侧骨髓检查来评估反应。 使用这些更轻松的响应标准，作者发表了很高的发表 完全缓解DCF的速率。 在我们的研究中有15名患者中， 可以评估14个反应的患者 骨硬化无法评估骨髓反应。 所有患者都有 外周血计数的快速归一化和所有14个 发现骨髓评估的患者的数量很少（较少 残留毛细细胞的总骨髓细胞的5％ 完成治疗。 在14位可评估患者中，只有一个 患者患了治疗的进行性疾病。 单人 弥漫性骨硬化患者的无效患者患有贫血 增加与进行性的血清可溶性IL-2受体水平 毛细胞白血病。 这些患者正在接受治疗 分别为2-氯脱氧腺苷和干扰素-Alfa。 虽然 对DCF和干扰素组合的初始响应率似乎 仅比单独使用DCF观察到的要好得多，响应持续时间可能 更长。 其余患者继续受到遵循 响应持续时间的确定。