Prognostic Value of the Immunological Subtypes of Adolescent and Adult T-Cell Lymphoblastic Lymphoma; an Ultra-High-Risk Pro-T/CD2(−) Subtype

SIMPLE SUMMARY: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and aggressive with no practical risk model defined. Considering the controversies over the prognostic value of T-LBL immunological subtypes, we re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia protocols, with 85.7% with complete remissions. To the best of our knowledge, this is the largest study of T-LBL diagnosed by flow-cytometry of the material obtained by fine-needle aspiration biopsy. We show that (1) CD2 status and age are powerful independent prognostic factors influencing overall survival and the risk of treatment failure; (2) the early/pro-T/CD2(−) subtype is associated with extremely poor outcomes; and (3) poor outcomes in ETP vs. non-ETP are strikingly consistent with the pro-T CD2(−) subtype. The lack of CD2 expression in T-LBL emerges as a new marker of an ultra-high-risk of treatment failure. We show here that ETP is a non-uniform entity, where the outcome depends on the CD2 status. ABSTRACT: (1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matter of controversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age > 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only (>35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned.