Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group.
Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group.
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播散性朗格汉斯细胞组织细胞增多症的治疗策略。
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
S. Ladisch
中科院分区：
文献类型：
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作者：
H. Gadner;A. Heitger;N. Grois;I. Gatterer;S. Ladisch
朗格汉斯细胞组织细胞增多症（LCH）的治疗仍然存在问题。为了检验快速开始和长期持续化疗可以提高生存率并减少播散性 LCH 的复发和晚期后果这一假设，我们完成了一项前瞻性临床试验 (DAL HX-83)。 106 名新诊断患者被分为三个风险组（A：多灶性骨病 [n = 28]；B：软组织受累，无器官功能障碍 [n = 57]；C：器官功能障碍 [n = 21]）。所有患者均接受相同的初始 6 周治疗（依托泊苷 [VP-16]、泼尼松和长春花碱），并继续治疗 1 年，根据诊断时的分层略有调整。所有患者均口服 6-巯基嘌呤和 8 次长春花碱和泼尼松脉冲，B 组添加 VP-16，C 组添加 VP-16 和甲氨蝶呤。A 组和 B 组分别有 89% 和 91% 的患者以及受影响最严重的 C 组 67% 的患者实现了疾病完全缓解。缓解速度很快（中位 4 个月）并且与疾病严重程度无关。初次缓解后复发率较低（A、B 和 C 组分别为 12%、23% 和 42%）；总体而言，77% 的患者没有复发。 20% 的患者诊断后出现永久性后果。开始治疗后仅有 10% 的患者出现尿崩症。死亡率 (9%) 仅限于 B 组（两名患者）和 C 组（八名患者）。最后，在接受 DAL HX-83 治疗的 106 名患者中，没有一人出现恶性肿瘤（中位随访时间 6 年零 9 个月）。活动性疾病持续时间较短、复发率和永久性后果较低以及预后不良患者的生存率提高，支持在诊断为播散性 LCH 后迅速开始预定的长期治疗的策略。
Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and long-term continuation of chemotherapy can improve survival and reduce recurrence and late consequences of disseminated LCH, we have completed a prospective clinical trial (DAL HX-83). One hundred six newly diagnosed patients were stratified into three risk groups (A: multifocal bone disease [n = 28]; B: soft tissue involvement without organ dysfunction [n = 57]; C: organ dysfunction [n = 21]). All patients received an identical initial 6-week treatment (etoposide [VP-16], prednisone, and vinblastine), and continuation treatment for 1 year, slightly adapted according to stratification at diagnosis. It included oral 6-mercaptopurine and eight pulses of vinblastine and prednisone for all patients, plus VP-16 in group B and VP-16 and methotrexate in group C. Eighty-nine percent and 91% of patients in groups A and B and 67% of the most severely affected group C, achieved complete resolution of disease. The speed of resolution was rapid (median 4 months) and independent of disease severity. The frequency of recurrence after initial resolution was low (12%, 23%, and 42% in groups A, B and C); overall fully 77% of patients have remained free of recurrence. Permanent consequences developed after diagnosis in 20% of the patients. Diabetes insipidus after initiation of treatment occurred in only 10% of patients. Mortality (9%) was limited to patients of groups B (two patients) and C (eight patients). Finally, among the 106 patients treated by DAL HX-83 none have developed a malignancy (median follow-up 6 years, 9 months). The shorter duration of active disease, low rate of recurrence and permanent consequences, and improved survival among patients with poor prognosis support the strategy of rapid initiation of a predefined prolonged treatment upon the diagnosis of disseminated LCH.