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.

我们给予脱氧共形霉素（dCF）和α干扰素（IFN-α） 对患有毛细胞白血病的患者进行治疗， 改善早期研究中观察到的反应率和持续时间， 每种药物单独。 本研究的进一步依据包括： 观察到IFN-α抵抗患者几乎一致地 响应于第二线路dCF。 由于存在一些重叠毒性， 我们决定按顺序用药而不是同时用药。 在这项研究中，我们通过对患者进行双侧 髂嵴骨髓活检和抽吸自外周血 在IFN-α或DCF治疗后迅速恢复正常， 在骨髓中变得片状，如果仅单侧， 已进行骨髓活组织检查。 使用IFN-α的其他研究 或dCF单独使用单侧骨髓检查来评价反应。 使用这些更宽松的反应标准，作者发表了高 dCF的完全缓解率。 在我们的研究中有15名患者， 14例可评价缓解，1例患者弥漫性 骨髓反应无法评估的骨痂。 所有患者均有 外周血细胞计数快速正常化， 骨髓可评估的患者被发现有非常小的数字（更少）， 超过总骨髓细胞结构的5%）的残留毛细胞， 完成治疗。 在14名可评价的患者中，只有1名 患者在停止治疗后发生疾病进展。 单 弥漫性骨质疏松的不可评价患者发生贫血， 血清可溶性IL-2受体水平增加与进行性 毛细胞白血病 这些患者正在接受治疗， 2-氯脱氧腺苷和α-干扰素。 虽然 dCF和干扰素联合治疗的初始应答率似乎 并不比单独使用DCF观察到的效果更好，响应持续时间可能 时间长点根本 其余患者继续接受随访， 响应持续时间的确定。