PO.CL09.02 · 临床研究
肝脾T细胞淋巴瘤gamma-delta型与alpha-beta型：临床病理特征和结局的比较研究
Hepatosplenic T-cell lymphoma gamma-delta versus alpha-beta: A comparative study of clinicopathologic features and outcomes
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：肝脾T细胞淋巴瘤（HSTCL）是一种侵袭性罕见的结外T细胞淋巴瘤。它最常起源于gammadelta T细胞，但alphabeta变异型也日益被认识。虽然gammadelta HSTCL被认为是原型形式并占大多数病例，但由于比较数据稀缺，alphabeta与gammadelta T细胞受体（TCR）表达的临床意义、生物学行为和预后影响仍不明确。我们开展本研究以比较两种亚型的临床病理特征。
方法：为研究临床病理特征、预后因素和总生存期（OS），我们汇编了HSTCL病例的汇总数据库。患者根据TCR表达分为两组：gammadelta-HSTCL和alphabeta-HSTCL。采用描述性统计概括基线特征。连续变量采用t检验比较，分类变量采用χ²检验比较。生存结局采用Kaplan-Meier方法分析。
结果：共识别出226例HSTCL患者，其中52例alphabeta型，174例gammadelta型。两个亚组的诊断中位年龄相似（30 vs 34岁），两组均有轻微男性优势，在gammadelta队列中更为明显（59% vs 72%）。两组中免疫抑制病史均常见（alphabeta 76% vs gammadelta 71%），暴露持续时间相当（中位4.7 vs 5年），至淋巴瘤发病的潜伏期相当（4 vs 5年）。两个队列均有高比例的肝脾肿大（alphabeta 100% vs gammadelta 99%）和骨髓浸润（两组均为100%）。血细胞减少常见且无显著差异：贫血（90% vs 95%）、白细胞减少（66% vs 61%）和血小板减少（86% vs 88%）。两种亚型的中位LDH水平均升高（797.5 vs 968 U/L）。中位总生存期同样很差——alphabeta型10个月，gammadelta型11个月。免疫表型上，两种亚型均高表达CD2、CD3、CD7、CD16、CD38和CD56。然而，CD5在alphabeta病例中表达更频繁（39% vs 14%，P=0.001），CD8阳性（57% vs 31%，P=0.005）和CD57（41% vs 5%，P=0.01）也是如此。8三体（33% vs 36%）和i/r 7（72% vs 75%）在两组中均普遍存在且相当。
结论：在这一大型比较队列中，alphabeta和gammadelta HSTCL在临床特征、免疫抑制模式、血细胞减少、器官受累、细胞遗传学异常和不良总生存方面表现出惊人的相似性。然而，显著的免疫表型差异——最显著的是alphabeta HSTCL中CD5、CD8和CD57的较高表达——提示两种由TCR定义的亚型之间存在潜在的生物学差异。这些发现强调，尽管两种形式在就诊时临床上无法区分且同样致命，但其独特的免疫谱可能具有诊断相关性，并可为未来靶向治疗策略的探索提供依据。
查看英文原文 English abstract
Introduction: Hepatosplenic T-cell lymphoma (HSTCL) is an aggressive rare extranodal T-cell lymphoma. It is most commonly derived from gammadelta T cells, though an alphabeta variant has been increasingly recognized. While gammadelta HSTCL is considered the prototypic form and accounts for the majority of cases, the clinical significance, biological behavior, and prognostic impact of alphabeta versus gammadelta T-cell receptor (TCR) expression remain poorly defined due to the scarcity of comparative data. We conducted this study to compare the clinicopathological characteristics of both subtypes.
Methods: To study the clinicopathologic characteristics, prognostic factors, and overall survival (OS), we compiled a pooled database of HSTCL cases. Patients were stratified into two groups based on TCR expression: gammadelta-HSTCL and alphabeta-HSTCL. Descriptive statistics were used to summarize baseline characteristics. Continuous variables were compared using t-test, and categorical variables by χ² test. Survival outcomes were analyzed using Kaplan-Meier methodology.
Results: A total of 226 patients with HSTCL were identified, 52 alphabeta and 174 gammadelta. The median age at diagnosis was similar between subgroups (30 vs 34 years), with a slight male predominance in both, more pronounced in the gammadelta cohort (59% vs 72%). A history of immune suppression was frequent in both groups (76% alphabeta vs 71% gammadelta), with comparable durations of exposure (median 4.7 vs 5 years) and latency to lymphoma onset (4 vs 5 years). Both cohorts had high rates of hepatosplenomegaly (100% alphabeta vs 99% gammadelta) and marrow infiltration (100% in both). Cytopenias were common and showed no significant differences: anemia (90% vs 95%), leukopenia (66% vs 61%), and thrombocytopenia (86% vs 88%). Median LDH levels were elevated in both subtypes (797.5 vs 968 U/L). Median overall survival was similarly poor-10 months in alphabeta and 11 months in gammadelta HSTCL. Immunophenotypically, the two subtypes shared high expression of CD2, CD3, CD7, CD16, CD38, and CD56. However, CD5 was more frequently expressed in alphabeta cases (39% vs 14%, P = 0.001) as well as CD8 positivity (57% vs 31%, P = 0.005) and CD57 (41% vs 5%, P = 0.01). Trisomy 8 (33% vs 36%) and i/r 7 (72% vs 75%) were prevalent and comparable between groups.
Conclusion: In this large comparative cohort, alphabeta and gammadelta HSTCL demonstrated strikingly similar clinical features, patterns of immune suppression, cytopenias, organ involvement, cytogenetic abnormalities, and dismal overall survival. However, significant immunophenotypic differences-most notably higher expression of CD5, CD8, and CD57 in alphabeta HSTCL-suggest underlying biologic divergence between the two TCR-defined subtypes. These findings highlight that while both forms remain clinically indistinguishable at presentation and equally lethal, their distinct immunoprofiles may have diagnostic relevance and could inform future exploration of targeted therapeutic strategies.
利益披露 Disclosure
P. A. Haddad, None..
S. Vutukuri, None..
A. Gupta, None.