PDF(Pubmed)
Abstract：
UNASSIGNED: Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This \"mixed\" entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH.
UNASSIGNED: This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children\'s Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival.
UNASSIGNED: Out of a cohort of 502 ECD patients, 69 (14%) had mixed ECD-LCH. Compared to isolated ECD, mixed ECD-LCH occurred more frequently in females (51 vs. 26%, p < 0.001) and in patients with multisystem disease (≥4 sites). Mixed ECD-LCH more frequently involved long bones (91 vs. 79%, p = 0.014), central nervous system (51 vs. 34%, p = 0.007), facial/orbit (52 vs. 38%, p = 0.031), lungs (43 vs. 28%, p = 0.009), hypothalamic/pituitary axis (51 vs. 26%, p < 0.001), skin (61 vs. 29%, p < 0.001), and lymph nodes (15 vs. 7%, p = 0.028); the BRAFV600E mutation was also more frequent in mixed ECD-LCH (81 vs. 59%, p < 0.001). Targeted treatments (BRAF and/or MEK inhibitors) induced response more frequently than conventional therapies (interferon-α, chemotherapy), either as first-line (77 vs. 29%, p < 0.001) or as any line (75 vs. 24%, p < 0.001). After a median follow-up of 71 months, 24 patients (35%) died. Survival probability was comparable between ECD alone and mixed ECD-LCH (log-rank p = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432).
UNASSIGNED: Mixed ECD-LCH is a multisystem disease driven by the BRAFV600E mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH.
UNASSIGNED: None.
UNASSIGNED: This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children\'s Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival.
UNASSIGNED: Out of a cohort of 502 ECD patients, 69 (14%) had mixed ECD-LCH. Compared to isolated ECD, mixed ECD-LCH occurred more frequently in females (51 vs. 26%, p < 0.001) and in patients with multisystem disease (≥4 sites). Mixed ECD-LCH more frequently involved long bones (91 vs. 79%, p = 0.014), central nervous system (51 vs. 34%, p = 0.007), facial/orbit (52 vs. 38%, p = 0.031), lungs (43 vs. 28%, p = 0.009), hypothalamic/pituitary axis (51 vs. 26%, p < 0.001), skin (61 vs. 29%, p < 0.001), and lymph nodes (15 vs. 7%, p = 0.028); the BRAFV600E mutation was also more frequent in mixed ECD-LCH (81 vs. 59%, p < 0.001). Targeted treatments (BRAF and/or MEK inhibitors) induced response more frequently than conventional therapies (interferon-α, chemotherapy), either as first-line (77 vs. 29%, p < 0.001) or as any line (75 vs. 24%, p < 0.001). After a median follow-up of 71 months, 24 patients (35%) died. Survival probability was comparable between ECD alone and mixed ECD-LCH (log-rank p = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432).
UNASSIGNED: Mixed ECD-LCH is a multisystem disease driven by the BRAFV600E mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH.
UNASSIGNED: None.
摘要：
■Erdheim-Chester病（ECD）是一种罕见的组织细胞增生症，可能与朗格汉斯细胞组织细胞增生症（LCH）重叠。此“混合”实体的特征不明确。我们在这里调查了临床表型，结果,以及大量混合ECD-LCH患者的预后因素。
这项回顾性研究是在法国和意大利的两个转诊中心进行的巴黎；迈耶儿童医院，佛罗伦萨)。我们纳入了2000-2022年诊断为ECD的儿童和成人，他们有活检证实的LCH，关于临床表现的可用数据，治疗和结果，至少随访一年。结果包括混合ECD-LCH和孤立ECD之间临床表现和生存率的差异；我们还调查了混合队列对治疗的反应和生存率的预测因素。使用Kaplan-Maier方法分析生存率，并通过长秩检验分析生存率差异。Cox回归模型用于评估年龄和性别对生存的潜在影响，并确定无反应和生存的预测因素。
■在502名ECD患者中，69(14%)有混合的ECD-LCH。与孤立的ECD相比，混合型ECD-LCH在女性中更常见(51vs.26%,p<0.001)和多系统疾病患者(≥4个部位)。混合ECD-LCH更频繁地涉及长骨（91与79%,p=0.014),中枢神经系统（51vs.34%,p=0.007),面部/眼眶（52vs.38%,p=0.031),肺（43vs.28%,p=0.009),下丘脑/垂体轴（51vs.26%,p<0.001)，皮肤（61vs.29%,p<0.001)，和淋巴结（15与7%,p=0.028）；BRAFV600E突变在混合ECD-LCH中也更频繁（81vs.59%,p<0.001)。靶向治疗（BRAF和/或MEK抑制剂）比常规治疗（干扰素-α，化疗)，要么作为第一行(77vs.29%,p<0.001)或任何行(75vs.24%,p<0.001)。经过71个月的中位随访，24例患者(35%)逝世亡。单独ECD和混合ECD-LCH之间的生存概率相当（log-rankp=0.948）。在多变量分析中，诊断年龄（HR1.052，95%CI1.008-1.096），相关血液学状况（HR3.030，95%CI1.040-8.827），治疗失败（HR9.736，95%CI2.919-32.481）与死亡风险增加相关，而溶解性骨病变的风险较低（HR0.116，95％CI0.031-0.432）。
■混合ECD-LCH是由BRAFV600E突变驱动的多系统疾病，靶向治疗是有效的。诊断时的年龄，骨损伤模式,相关的血液学状况，治疗失败是ECD-LCH混合型患者死亡的主要预测因素。
■无。
这项回顾性研究是在法国和意大利的两个转诊中心进行的巴黎；迈耶儿童医院，佛罗伦萨)。我们纳入了2000-2022年诊断为ECD的儿童和成人，他们有活检证实的LCH，关于临床表现的可用数据，治疗和结果，至少随访一年。结果包括混合ECD-LCH和孤立ECD之间临床表现和生存率的差异；我们还调查了混合队列对治疗的反应和生存率的预测因素。使用Kaplan-Maier方法分析生存率，并通过长秩检验分析生存率差异。Cox回归模型用于评估年龄和性别对生存的潜在影响，并确定无反应和生存的预测因素。
■在502名ECD患者中，69(14%)有混合的ECD-LCH。与孤立的ECD相比，混合型ECD-LCH在女性中更常见(51vs.26%,p<0.001)和多系统疾病患者(≥4个部位)。混合ECD-LCH更频繁地涉及长骨（91与79%,p=0.014),中枢神经系统（51vs.34%,p=0.007),面部/眼眶（52vs.38%,p=0.031),肺（43vs.28%,p=0.009),下丘脑/垂体轴（51vs.26%,p<0.001)，皮肤（61vs.29%,p<0.001)，和淋巴结（15与7%,p=0.028）；BRAFV600E突变在混合ECD-LCH中也更频繁（81vs.59%,p<0.001)。靶向治疗（BRAF和/或MEK抑制剂）比常规治疗（干扰素-α，化疗)，要么作为第一行(77vs.29%,p<0.001)或任何行(75vs.24%,p<0.001)。经过71个月的中位随访，24例患者(35%)逝世亡。单独ECD和混合ECD-LCH之间的生存概率相当（log-rankp=0.948）。在多变量分析中，诊断年龄（HR1.052，95%CI1.008-1.096），相关血液学状况（HR3.030，95%CI1.040-8.827），治疗失败（HR9.736，95%CI2.919-32.481）与死亡风险增加相关，而溶解性骨病变的风险较低（HR0.116，95％CI0.031-0.432）。
■混合ECD-LCH是由BRAFV600E突变驱动的多系统疾病，靶向治疗是有效的。诊断时的年龄，骨损伤模式,相关的血液学状况，治疗失败是ECD-LCH混合型患者死亡的主要预测因素。
■无。
