EVALUATION OF 2'-DCF IN RECOMBINANT LEUKOCYTE IFN ALPHA IN HAIRY CELL LEUKEMIA

毛细胞白血病重组白细胞 IFN α 中 2-DCF 的评估

• 批准号: 3874518
• 负责人: R G STEIS
• 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/3874518
• 关键词: antileukemic agent; antineoplastic antibiotics; antineoplastics; clinical trials; combination chemotherapy; deoxycoformycin; drug adverse effect; enzyme inhibitors; hairy cell leukemia; human subject; human therapy evaluation; human tissue; immunosuppressive; interferons; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy

We administered deoxycoformycin (dCF) and interferon-alfa 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 interferon- alfa 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 interferon-alfa 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 interferon-alfa 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 of dCF. Of 15 patients entered in our study, 14 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. With a median follow-up now of 35 months, no patient has had an increase in the number of hairy cells in the bone marrow or any change in the peripheral blood. 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. These patients continue to be followed for determination of response duration.

我们给药脱氧共形霉素（DCF）和干扰素-α顺序， 毛细胞白血病患者，试图提高反应 在早期单独使用每种药物的研究中观察到的速率和持续时间。 本研究的进一步理论基础包括观察到干扰素- 对阿尔法耐药的患者对二线治疗的反应几乎一致， dCF。 由于有一些重叠的毒性，我们决定给予 连续用药而不是同时用药。 在这项研究中，我们评估了 患者通过双侧髂嵴骨髓 由于外周血在术后迅速恢复正常， 无论是干扰素-阿尔法或DCF治疗，但疾病成为斑片状在 如果只有单侧骨髓活检， 被执行。 其他使用干扰素-α或DCF单独使用的研究 单侧骨髓检查评价反应。 使用这些更多 宽松的反应标准，作者发表了高比率的完整的 dCF的缓解。 在我们研究的15例患者中，14例可评价 骨髓反应。 所有患者外周血淋巴细胞均迅速恢复正常， 血细胞计数和所有14个骨髓可评估的患者被发现有非常 少量（小于总骨髓细胞的5%）残留的 毛细胞在治疗结束时。 现在的平均随访时间是 35个月内，没有患者的毛细胞数量增加 骨髓或外周血的任何变化。 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 这些患者继续接受随访，以确定 响应持续时间。