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1.
Am J Hematol ; 98(3): 388-397, 2023 03.
Article in English | MEDLINE | ID: mdl-36588403

ABSTRACT

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8 cycles of CHOP(-like) therapy and 22% received 3-4 cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4 cycles vs. 6-8 cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4 cycles versus 6-8 cycles of CHOP(-like) therapy were comparable.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Large-Cell, Anaplastic , Lymphoma, T-Cell, Peripheral , Adult , Humans , Middle Aged , Lymphoma, T-Cell, Peripheral/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Treatment Outcome , Lymphoma, Large B-Cell, Diffuse/drug therapy , Stem Cell Transplantation , Doxorubicin , Prednisone/adverse effects , Vincristine , Cyclophosphamide
2.
Blood Adv ; 2(19): 2533-2542, 2018 10 09.
Article in English | MEDLINE | ID: mdl-30291111

ABSTRACT

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) constitutes a heterogeneous category of lymphomas, which do not fit into any of the specifically defined T-cell lymphoma entities. Both the pathogenesis and tumor biology in PTCL-NOS are poorly understood. Protein expression in pretherapeutic PTCL-NOS tumors was analyzed by proteomics. Differentially expressed proteins were compared in 3 distinct scenarios: (A) PTCL-NOS tumor tissue (n = 18) vs benign lymphoid tissue (n = 8), (B) clusters defined by principal component analysis (PCA), and (C) tumors from patients with chemosensitive vs refractory PTCL-NOS. Selected differentially expressed proteins identified by proteomics were correlated with clinico-pathological features and outcome in a larger cohort of patients with PTCL-NOS (n = 87) by immunohistochemistry (IHC). Most proteins with altered expression were identified comparing PTCL-NOS vs benign lymphoid tissue. PCA of the protein profile defined 3 distinct clusters. All benign samples clustered together, whereas PTCL-NOS tumors separated into 2 clusters with different patient overall survival rates (P = .001). Differentially expressed proteins reflected large biological diversity among PTCL-NOS, particularly associated with alterations of "immunological" pathways. The 2 PTCL-NOS subclusters defined by PCA showed disturbance of "stress-related" and "protein metabolic" pathways. α-Enolase 1 (ENO1) was found differentially expressed in all 3 analyses, and high intratumoral ENO1 expression evaluated by IHC correlated with poor outcome (hazard ratio, 2.09; 95% confidence interval, 1.17-3.73; P = .013). High expression of triosephosphate isomerase (TPI1) also showed a tendency to correlate with poor survival (P = .057). In conclusion, proteomic profiling of PTCL-NOS provided evidence of markedly altered protein expression and identified ENO1 as a novel potential prognostic marker.


Subject(s)
Lymphoma, T-Cell, Peripheral/metabolism , Lymphoma, T-Cell, Peripheral/mortality , Proteome , Proteomics , Aldehyde Dehydrogenase, Mitochondrial/metabolism , Biomarkers, Tumor/metabolism , Chromatography, Liquid , Computational Biology , DNA-Binding Proteins/metabolism , Female , Humans , Lymphoid Tissue/metabolism , Lymphoma, T-Cell, Peripheral/genetics , Male , Phosphopyruvate Hydratase/metabolism , Prognosis , Proteomics/methods , Tandem Mass Spectrometry , Tumor Suppressor Proteins/metabolism
3.
Br J Haematol ; 178(5): 739-746, 2017 09.
Article in English | MEDLINE | ID: mdl-28485010

ABSTRACT

Anaplastic large cell lymphomas (ALCLs) are rare CD30+ peripheral T-cell lymphomas (PTCLs) classified according to the expression of the anaplastic lymphoma kinase (ALK+) protein or not (ALK-). We have analysed the outcome and risk factors for survival in a population-based bi-national cohort of patients with systemic ALK+ ALCL. A total of 122 adult (≥18 years) patients diagnosed with ALK+ ALCL between 2000 and 2010 were identified from the Danish and Swedish lymphoma registries, representing 0·4% of all lymphomas. The median age of the cohort was 40 years (range 18-85). The 5-year overall survival and progression-free survival (PFS) was 78% and 64%, respectively. Age was strongly associated with outcome, and only bone marrow (BM) involvement was independently associated with poorer PFS in multivariate analysis (Hazard Ratio [HR] = 8·57, P < 0·001). Age stratification of the patients demonstrated an association between treatment with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone) and improved overall survival for patients aged 41-65 years, even when adjusted for risk factors (HR = 0·38, P = 0·047). Our results suggest that the addition of etoposide to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) in the treatment for ALK+ ALCL seems reasonable in this age group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large-Cell, Anaplastic/drug therapy , Receptor Protein-Tyrosine Kinases/metabolism , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Anaplastic Lymphoma Kinase , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/metabolism , Cyclophosphamide/administration & dosage , Denmark/epidemiology , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Lymphoma, Large-Cell, Anaplastic/diagnosis , Lymphoma, Large-Cell, Anaplastic/mortality , Male , Middle Aged , Prednisolone/administration & dosage , Prognosis , Registries , Risk Factors , Sweden/epidemiology , Treatment Outcome , Vincristine/administration & dosage , Young Adult
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