Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country

Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas

“…Due to the frequent overlapping of clinical, pathological, phenotypic and molecular-genetic findings among the four main histological subtypes of nodal MTCL recognized by the latest WHO Classification of Hematopoietic Neoplasms (WHO-2016) and taking into account the high rate of therapeutic failure with conventional chemotherapy regimens, the discovery of new diagnostic and prognostic biomarkers is fundamental [ 2 , 15 ]. In this sense, our group recently demonstrated that peripheral monocyte count ≥ 1.5 × 10 9 /L at diagnosis, overexpression of the CCNA2 gene and CHEK1 protein, high tissue expression of the GATA-3 gene and mutations involving the TET-2 gene may be potential biomarkers capable of assisting in the diagnostic discrimination of the different nodal MTCL histological subtypes.…”

“…Such new genetic-molecular biomarkers may also represent specific targets for therapeutic intervention. The high concentration of P -glycoprotein (Pgp) in MTCL tumor cells, as well as the frequent inactivation of tumor suppressor genes, such as TP53 and p15INK4b / p16INK4a , confer a multidrug resistance phenotype (MDR), thus explaining the poor results achieved with regimens based on anthracyclic agents and vinca alkaloids in the up-front therapy of nodal MTCL [ 2 , 20 – 23 ]. Aiming to improve the therapeutic results, new target-drugs have been considered for the management of nodal MTCL, specifically for cases with follicular T-helper (THf) origin.…”

“…Mature T-cell lymphomas (MTCL) represents a heterogeneous group of post-thymic T-cell malignant neoplasms that are highly aggressive and frequently resistant to chemotherapy based on anthracyclic agents. Patients with MTCL have an estimated 5-year overall survival (OS) around 30–40% [ 1 , 2 ]. It accounts for 15% of all non-Hodgkin’s lymphomas (NHL), and according to the 2016-World Health Organization (WHO) Classification of Hematopoietic and Lymphoid Tissue Neoplasms, are categorized as predominantly nodal, extra nodal, primary cutaneous and disseminated or leukemic [ 1 ].…”

“…It accounts for 15% of all non-Hodgkin’s lymphomas (NHL), and according to the 2016-World Health Organization (WHO) Classification of Hematopoietic and Lymphoid Tissue Neoplasms, are categorized as predominantly nodal, extra nodal, primary cutaneous and disseminated or leukemic [ 1 ]. Although rare, these tumors show characteristic geographic distribution, being more prevalent in East Asia and South America, where it represents up to 25% of all NHL [ 1 , 2 ].…”

“…The nodal subgroup (nMTCL) encompasses approximately 60–70% of MTCL cases, comprising four main histopathological variants, including peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); angioimmunoblastic T-cell lymphoma (AITL) and other nodal MTCL with T-helper follicular phenotype (nMTCL-THf), such as the follicular T-cell lymphoma with t(5;9)(q33;q22)— ITK/SYK rearrangement; and ALK1 ( anaplastic lymphoma kinase-1 ) positive and negative systemic anaplastic large cell lymphomas (sALCL) [ 1 ]. Commonly, patients with nMTCL present unfavorable biological features at diagnosis, including inactivation of the tumor suppressor genes TP53 and p15INK4b/p16INK4a , high concentration of P-glycoprotein (Pgp) into neoplastic cells and multi-drug resistance phenotype (MDR), which explain the high rates of therapeutic failure with CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens [ 2 ].…”