GRANULOCYTOPENIA AFTER COMBINED THERAPY WITH INTERFERON AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS - EVIDENCE FOR A SYNERGISTIC HEMATOLOGIC TOXICITY
GRANULOCYTOPENIA AFTER COMBINED THERAPY WITH INTERFERON AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS - EVIDENCE FOR A SYNERGISTIC HEMATOLOGIC TOXICITY
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DOI：
10.1016/s0002-9343(99)80186-7
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发表时间：
1995-10-01
影响因子：
5.9
通讯作者：
BONOMO, L
中科院分区：
文献类型：
--
作者：
CASATO, M;PUCILLO, LP;BONOMO, L
目的：本研究的目的是评估是否观察到的38例原发性混合型白细胞减少症谁是低剂量干扰素治疗是由于潜在的疾病或干扰素与其他药物的协同毒性。患者和方法：干扰素治疗的不良反应进行了监测，在38例受影响的II型原发性混合型白细胞减少症。患者每天或隔日接受300万单位（MU）重组干扰素-α 2a（35例患者）或天然干扰素-β（3例患者）治疗。治疗的持续时间范围在6和15个月之间;随访的总持续时间，包括治疗后，范围在8和93 months.RESULTS：35例单独用干扰素治疗的患者均未出现明显的血液学改变。此外，7例单独接受血管紧张素转换酶（ACE）抑制剂治疗的患者均未出现血液学毒性。三名接受干扰素和ACE抑制剂联合治疗的患者在开始治疗后几天发生了严重的粒细胞减少症。停药后1 ~ 2周粒细胞减少消失。恢复该药物联合治疗后，1例患者出现粒细胞减少症复发。在这3例患者中，干扰素单独治疗，或ACE抑制剂单药治疗，没有随后的粒细胞减少症。结论：虽然严重的血液毒性很少在低剂量干扰素治疗的患者中发展，粒细胞减少症发生在所有3例混合性白细胞减少症患者谁是低剂量干扰素-α 2a和ACE抑制剂的组合治疗。两种药物单独使用对我们的任何一位冷球蛋白血症患者都没有毒性，表明这种药物联合使用的严重血液学毒性风险很高，至少在患有这种疾病的患者中是这样。医生在对患有这种或其他可能需要降压治疗的疾病的患者使用干扰素治疗时，应该意识到这种危险。
PURPOSE The purpose of this study was to assess whether granulocytopenia observed in 3 of 38 patients with essential mixed cryoglobulinemia who were treated with low-dose interferon was due to the underlying disease or to synergistic toxicity of interferon with other drugs.PATIENTS AND METHODS: Adverse effects of interferon therapy were monitored in 38 patients affected with type II essential mixed cryoglobulinemia. Patients were treated with 3 million units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35 patients) or with natural interferon-beta (3 patients). The duration of treatment ranged between 6 and 15 months; the total duration of follow-up, including after therapy, ranged between 8 and 93 months.RESULTS: None of 35 patients treated with interferon alone developed significant hematologic alterations. In addition, none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors alone showed hematologic toxicity. Three patients who were treated with a combination of interferon and ACE inhibitors developed severe granulocytopenia a few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks after suspending therapy. Resumption of treatment with this drug combination produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon treatment alone, or ACE inhibitor monotherapy, was not followed by granulocytopenia.CONCLUSION: Although severe hematologic toxicity rarely develops in patients treated with low-dose interferon, granulocytopenia occurred in all 3 of our patients with mixed cryoglobulinemia who were treated with a combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug alone was toxic in any of our cryoglobulinemic patients, indicating a high risk of severe hematologic toxicity for this drug combination, at least in patients with this disease. Physicians should be aware of this danger when using interferon treatment in patients with this, or possibly other, disorder(s) that also require antihypertensive therapy.