LOW DOSE MITHRAMYCIN TREATMENT OF BONE PAIN IN SYSTEMIC MASTOCYTOSIS

低剂量光神霉素治疗系统性肥大细胞增多症骨痛

• 批准号: 6264960
• 负责人: JOSEPH H BUTTERFIELD
• 金额: $ 2.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264960
• 关键词: analgesia; bone disorder; clinical research; clinical trial phase I; human subject; human therapy evaluation; mastocytosis; mithramycin; pain

Bone involvement is a common, painful, and debilitating aspect of systemic masocytosis. It is not clear why systemic mastocytosis causes bone pain in the absence of fractures; however, long delays in making the diagnosis of systemic mastocytosis are not unusual and may allow progression of bone disease. Histopathologic patterns of bone marrow mast cell involvement have been identified as 1) focal mast cell aggregates in peritrabecular and perivascular areas often with increased numbers of eosinophils, and a dense network of reticulin fibers; 2) peritrabecular and perivascular sheets of mast cells accompanied by fibrosis and osteosclerosis; or 3) diffuse infiltration by atypical mast cells with marked hypoplasia of fat cells and blood precursors. This is a Phase I study to examine the effectiveness of low-dose mithramycin to relieve bone pain in patients with systemic mastocytosis. The clinical response to mithromycin will be evaluated by assessment of pain status and pain medication use prior to and following treatment. Functional status will be monitored with the Health Status Questionnaire (HSQ). Patient recruitment has been frustrating. The reason is not entirely clear, but I believe it is due to several factors: 1) patient resistance to pay expenses for travel to Rochester and preliminary costs for diagnosis of systemic mastocytosis; and 2) the normal ebb and flow of patients with rare disease who are seen at one institution. I have announced this protocol in the Mastocytosis Society Newsletter and have made announcements on the Mastocytosis Society's web page. I have been in touch with numerous physicians who refer patients with mastocytosis and have informed them of the study. I have also called patients directly to discuss the protocol.. I believe we will get the patient enrollment, but the time course of this enrollment is not clear.

骨骼受累是全身性肥大细胞增多症的一个常见、痛苦和使人虚弱的方面。 目前尚不清楚为什么系统性肥大细胞增多症在没有骨折的情况下会引起骨痛;然而，系统性肥大细胞增多症的诊断长期延误并不罕见，可能会导致骨病的进展。 骨髓肥大细胞受累的组织学模式已被确定为：1）骨小梁周围和血管周围区域的局灶性肥大细胞聚集，通常伴有嗜酸性粒细胞数量增加和网状纤维致密网络; 2）骨小梁周围和血管周围肥大细胞片，伴有纤维化和骨质疏松;或3）非典型肥大细胞弥漫性浸润，伴有脂肪细胞和血液前体细胞明显发育不全。这是一项I期研究，旨在检查低剂量光辉霉素缓解全身性肥大细胞增多症患者骨痛的有效性。将通过评估治疗前后的疼痛状态和止痛药使用情况来评价对红霉素的临床反应。将使用健康状况问卷（HSQ）监测功能状态。患者招募一直令人沮丧。 原因尚不完全清楚，但我相信这是由于几个因素：1）患者不愿支付前往罗切斯特的费用和诊断系统性肥大细胞增多症的初步费用; 2）在一个机构就诊的罕见疾病患者的正常潮起潮落。 我已经在肥大细胞增多症协会通讯中宣布了这一方案，并在肥大细胞增多症协会的网页上发表了声明。 我已经与许多推荐肥大细胞增多症患者的医生联系，并告知他们这项研究。 我也直接打电话给病人讨论方案。我相信我们将获得患者入组，但该入组的时间进程尚不清楚。