Hong Y, Wan W L, Li M, Wang H, Dong F, Jing H M, Ke X Y, Zhu M X
Department of Hematology, Peking University Third Hospital, Beijing 100191, China.
Department of Pathology, Peking University Third Hospital, Beijing 100191, China.
Zhonghua Yi Xue Za Zhi. 2023 Aug 8;103(29):2258-2265. doi: 10.3760/cma.j.cn112137-20230223-00259.
To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMBFCgroup (115 cases), the BMBFCgroup (50 cases), the BMBFCgroup (8 cases, the results did not include in statistical analysis because of small sample size), and the BMBFCgroup (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, =0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMBFCgroup than those in the BMBFCgroup and the BMBFCgroup (all <0.05). The treatment response rate in BMBFCgroup was 63.5% (73/115), which was lower than those in BMBFCgroup (88.0%, 44/50, =0.048) and BMBFCgroup (90.0%, 215/239, =0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all <0.05). FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.
分析流式细胞术(FC)在伴有骨髓受累(BMI)的弥漫性大B细胞淋巴瘤(DLBCL)中的诊断和预后价值。回顾性分析2012年12月至2022年6月北京大学第三医院血液科412例新诊断DLBCL患者的临床资料,其中男性243例,女性169例,年龄64(28 - 92)岁。所有患者均接受骨髓活检(BMB)和骨髓FC检查。对FC检测为BMI阳性的患者进一步行荧光原位杂交(FISH)基因分析。评估BMB和FC检测BMI的阳性率及一致性。根据BMB和FC检查结果,将所有患者分为四组:BMB⁺FC⁺组(115例)、BMB⁺FC⁻组(50例)、BMB⁻FC⁺组(8例,因样本量小未纳入统计分析)、BMB⁻FC⁻组(239例)。分析不同组的临床特征、治疗有效率、5年生存率及FC免疫表型特征。412例DLBCL患者中,BMB和FC检测BMI的阳性率分别为29.9%(123/412)和40.0%(165/412)。BMB与FC之间具有良好的一致性(Kappa = 0.841,P = 0.001)。BMB⁺FC⁺组中结外受累≥2处、脾肿大、巨大肿块、Ki-67评分较高、国际预后指数(IPI)评分较高、血小板减少及乳酸脱氢酶水平升高的患者数量比BMB⁺FC⁻组和BMB⁻FC⁻组更常见(均P < 0.05)。BMB⁺FC⁺组的治疗有效率为63.5%(73/115),分别低于BMB⁺FC⁻组(阳性组)(88.0%,44/50,P = 0.048)和BMB⁻FC⁻组(阴性组)(90.0%,215/239,P = 0.032)。三组的5年总生存率分别为(53.6±9.7)%、(72.5±8.6)%和(75.2±7.6)%,差异有统计学意义(P = 0.037)。根据骨髓FISH结果,102例诊断为未另行特指(NOS),48例诊断为双打击淋巴瘤(DHL),15例诊断为三打击淋巴瘤(THL)。与NOS亚型相比,DHL或THL亚型的肿瘤细胞侧向散射(SSC)增高比例更高、CD10表达阳性率更高、CD38强表达及CD56表达阳性率更高,表面免疫球蛋白轻链限制比例更低(均P < 0.05)。FC在诊断伴有BMI的DLBCL方面与BMB具有良好的一致性。结合FISH检测,FC有助于DHL和THL的辅助诊断和风险分层,并为伴有BMI的DLBCL的预后评估提供参考。