Mature T cell lymphomas (MTCLs) have worse prognosis, and in contrast to B cell lymphomas, there is no universal marker like CD20 with exception of ALK and CD30, which are present in proportion of MTCL only. Up to now, ALK is traditionally associated with good prognosis in ALCLs, and there are some evidences that CD30-positive T cell or B cell lymphomas have better prognosis. In our retrospective, population-based analysis, we analyzed the real clinical value of ALK and CD30 in the most frequent MTCL subtypes. Between 2000 and 2017, we identified 732 patients with newly diagnosed ALCL, AITL, or PTCL-NOS. Among them, 207 ALCL patients were with known ALK, whereas 61 AITL and 238 PTCL-NOS with known CD30 expression. There were 69/207 (33.3%) ALK + ALCLs, who displayed better 5-year PFS (65.6% vs. 36.2%) (p .001) and 5-year OS (71.5% vs. 45.9%) (p .002) compared to ALK - ; ALK + patients were significantly younger (median 48 vs. 60 years; p < 0.001). For patients ≥ 60 years, 5-year PFS (38.5% vs. 31.2%) and 5-year OS (38.5% vs. 39.6%) were similar between ALK + vs. ALK - patients. For AITL and PTCL-NOS, there were 44/61 (72.1%) and 120/238 (50.4%) CD30 + samples, and difference in CD30 expression was significant (p .02). AITL patients had 5-year OS of 43.8% vs. 55.7% (p 0.848) and 5-year PFS of 36.7% vs. 29.4% (p .624) for CD30 + vs. CD30 - patients, whereas PTCL-NOS had 5-year OS of 35.7% vs. 34.3% (p .318) and 5-year PFS of 29.3% vs. 22.5% (p.114) for CD30 + vs. CD30 - cases. We conclude that ALK in ALCLs (≥ 60 years) and CD30 expression in PCTL-NOS and AITL have only limited prognostic value.

Department of Clinical Hematology Teaching Hospital Ostrava Ostrava Czech Republic

Department of Hematology University Hospital Olomouc Olomouc Czech Republic

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Jihlavska 20 62500 Brno Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine Charles University and Faculty Hospital in Motol Prague Czech Republic

Department of Pathology Masaryk University and University Hospital Brno Brno Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

Internal Clinic of Haematology University Hospital Kralovske Vinohrady Prague Charles University Prague 3Rd Faculty of Medicine Prague Czech Republic

St Department of Medicine 1st Medical Faculty Charles University and General University Hospital Prague Czech Republic

Th Department of Internal Medicine Hematology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

The Fingerland Department of Pathology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Zobrazit více v PubMed

Petrich AM, Helenowski IB, Bryan LJ et al (2015) Factors predicting survival in peripheral T-cell lymphoma in the USA: a population-based analysis of 8802 patients in the modern era. British Journal of Heamatology 168:708–718 DOI

Ellin F, Landström J, Jerkeman M, Relander T (2014) Real-word data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood 124(10):1570–1577 DOI

Pedersen MB, Hamilton-Dutoit SJ, Bendix K et al (2015) Evaluation of clinical trial eligibility and prognostic indices in a population-based cohort of systemic peripheral T-cell lymphomas from the Danish Lymphoma Registry. Hematological Oncology  33:120–128

Janikova A, Chloupkova R, Campr V et al (2019) First-line therapy for T cell lymphomas: a retrospective population-based analysis of 906 T cell lymphoma patients. Ann Hematol 98(8):1961–1972 DOI

Gambacorti Passerini C, Farina F, Stasia A et al ( 2014) Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. J Natl Cancer Inst 106(2):djt378.  https://doi.org/10.1093/jnci/djt378

Mossé YP, Voss SD, Lim MS et al (2017) Targeting with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: a Children’s Oncology Study Group. J Clin Oncol 35(28):3215–3221 DOI

Horwitz SM, Advani RH, Bartlett NL et al (2014) Objective responses in relapses T-cell lymphomas with single-agent brentuximab vedotin. Blood 123:3095–3100 DOI

Morris SW, Kirstein MN, Valentine MB et al (1994) Fusion of kinase gene, ALK, to a nuclear protein gene, NPM, in non-Hodgkin´s lymphoma. Science 263(5151):1281–1284 DOI

Lobello C, Bikos V, Janikova A, Pospisilova S ( 2018) The role of oncogenic tyrosine kinase NPM-ALK in genomic instability. Cancers 10:64. https://doi.org/10.3390/cancers10030064

Savage KJ, Harris NL, Vose JM et al (2008) ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood 111:5496–5504 DOI

Sibon D, Fournier M, Briére J et al (2012) Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d´Étude des Lymphomes de l´Adulte Trials. J Clin Oncol 30:3939–3946 DOI

Dürkop H, Latza U, Hummel M et al (1992) Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin´s disease. Cell 68(3):421–427 DOI

Karube K, Aoki R, Nomura Y et al (2008) Usefulness of flow cytometry for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas: analysis of 490 cases. Pathol Int 58:89–97 DOI

Rodriguez-Pinilla SM, Sanchez ME, Rodriguez J et al (2013) Loss of TCR-beta F1 and/or EZRIN expression is associated with unfavorable prognosis in nodal peripheral T-cell lymphomas. Blood Cancer J 3(e111):1–8

Onaindia A, Martinez N, Montes-Moreno S et al ( 2016) CD30 expression by B and T cells. A frequent finding in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma-not otherwise specified. Am J Surg Pathol 40:378–85

Savage KJ, Al-Rajhi N, Voss N et al (2006) Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol 17(1):123–130 DOI

Hu S, Xu-Monette Z, Balasubramanyam A et al (2013) CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood 121(14):2715–2724 DOI

Bisig B, de Reyniés A, Bonnet Ch et al (2013) CD-30 positive T-cell lymphomas share molecular and phenotypic features. Hematologica 98(8):1250–1258 DOI

Piccaluga PP, Fuligni F, De Leo A et al (2013) Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study. J Clin Oncol 32(24):3019–3025 DOI

Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the Committee on Non-Hodgkin’s Disease Staging Classification. Cancer Res 31:1860–1861 PubMed

Sykorova A, Belada D, Smolej L et al (2010) Staging of non-Hodgkin’s lymphoma –recommendations of the Czech Lymphoma Study Group. Klin Onkol 23:146–154 PubMed

Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17:1244

Cheson BD, Pfistner B, Juweid ME et al (2007) International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–86

Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer (IARC); 4th Edition, Lyon

Swerdlow SH, Campo E, Pileri SA et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390 DOI

Horwitz S, O´Connor OA, Pro B et al (2019) Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global double-blind, randomized, phase 3 trial. Lancet 393:229–40

Marchi E, O´Connor OA (2020) The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management. CA Cancer J Clin 70:47–70

Morel A, Brière J, Lamant L et al (2017) Long-term outcomes of adults with first-relapsed/refractory systemic anaplastic large-cell lymphoma in the pre-brentuximab vedotin era: A LYSA/SFGM-TC study. Eur J Cancer 83:146–153 DOI

Perkins SL, Pickering D, Lowe EJ et al (2005) Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation. Br J Haematol 131(5):624–627 DOI

Zhou X, Shou J, Sheng J et al (2019) Molecular and clinical analysis of Chinese patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer. Cancer Sci 110(10):3382–3390 DOI

Rodriguez-Pinilla SM, Domingo-Domenech E, Climent F et al (2021) Clinical and pathological characteristics of peripheral T-cell lymphomas in a Spanish population: a retrospective study. Br J Haematology 192:82–99 DOI

Pierce JMR, Mehta A (2017) Diagnostic, prognostic and therapeutic role of CD30 in lymphoma. Expert Rev Hematol 10:29–37 DOI

Federico M, Bellei M, Marcheselli L et al (2018) Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS). A new prognostic model developed by the International T cell Project Network. British Journal of Haematology 181:760–69

Salas MQ, Climent F, Tapia G et al (2020) Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution. Biomarkers 25(1):69–75 DOI

Barta SK, Gong JZ, Porcu P (2019) Brentuximab vedotin in the treatment of CD30+ PTCL. Blood 134(26):2339–2345 DOI

Karube K, Kakimoto Y, Tonozuka Y, Ohshima K (2021) The expression of CD30 and its clinico-pathologic significance in peripheral T-cell lymphomas. Expert Rev Hematol 14:777–787 DOI