Yu Li, Tu Meifeng, Cortes Jorge, Xu-Monette Zijun Y, Miranda Roberto N, Zhang Jun, Orlowski Robert Z, Neelapu Sattva, Boddu Prajwal C, Akosile Mary A, Uldrick Thomas S, Yarchoan Robert, Medeiros L Jeffrey, Li Yong, Fajgenbaum David C, Young Ken H
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Hematology, The Second Affiliate Hospital of Nanchang University, Nanchang, China.
Blood. 2017 Mar 23;129(12):1658-1668. doi: 10.1182/blood-2016-11-748855. Epub 2017 Jan 18.
Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV-8-associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic response of 96 patients (43 with UCD and 53 with iMCD) with HIV-/HHV-8-negative CD compared with 51 HIV-/HHV-8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD3 lymphocytes (median, 58.88 ± 20.57) and lower frequency of CD19/CD5 (median, 5.88 ± 6.52) were observed in iMCD patients compared with UCD patients (median CD3 cells, 43.19 ± 17.37; median CD19/CD5 cells, 17.37 ± 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progression-free survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.
卡斯特曼病（CD）由3种了解甚少的淋巴增殖性变体组成，它们具有一些共同的组织病理学特征。单中心性CD（UCD）局限于单个淋巴结区域。多中心性CD（MCD）由于细胞因子失调而表现出全身炎症症状和器官功能障碍，且累及多个淋巴结区域。人类疱疹病毒8型（HHV - 8）在免疫功能低下的个体中，如感染HIV的患者中，可导致MCD（HHV - 8相关的MCD）。然而，超过50%的MCD病例HIV和HHV - 8呈阴性（定义为特发性[iMCD]）。CD的临床和生物学行为仍未得到充分阐明。在此，我们分析了74例患者（43例UCD患者和31例iMCD患者）的临床病理特征，以及96例HIV/HHV - 8阴性CD患者（43例UCD患者和53例iMCD患者）与51例HIV/HHV - 8阳性患者的治疗反应。全身炎症症状和炎症因子升高在iMCD患者中比UCD患者更常见。iMCD患者（77.0%）的骨髓异常特征比UCD患者（45%）更频繁；最常见的是浆细胞增多，在3%至30.4%的骨髓细胞中可见。在淋巴结中，与UCD患者相比，iMCD患者观察到更高数量的CD3淋巴细胞（中位数，58.88±20.57）和更低频率的CD19/CD5（中位数，5.88±6.52）（CD3细胞中位数，43.19±17.37；CD19/CD5细胞中位数，17.37±15.80）。对于UCD患者，完整手术切除是更好的选择。与利妥昔单抗相比，西妥昔单抗对iMCD的完全缓解比例更高，无进展生存期（PFS）更长。中心性、组织病理学类型和贫血对PFS有显著影响。这项研究表明，CD代表了一组具有不同免疫表型特征和治疗反应的异质性疾病。
