Large T-cell Lymphoma Research Articles

Recurrence of an erythrodermic mycosis fungoides as a biologically indolent anaplastic large T-cell lymphoma initially misdiagnosed as being of donor origin.

Recurrence of an erythrodermic mycosis fungoides as a biologically indolent anaplastic large T-cell lymphoma initially misdiagnosed as being of donor origin.

Programmed Death Ligand 1 (PD-L1) Expression in Lymphomas: State of the Art.

The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis. These therapies restore T-cell antitumor immune response by releasing T-lymphocytes from the inhibitory effects of tumor cells. Immune checkpoint therapies have completely changed the management of patients with solid cancers. This therapeutic strategy is less used in hematological malignancies, although good results have been achieved in some settings, such as refractory/relapsed classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Variable results have been obtained in diffuse large B-cell lymphoma and T-cell lymphomas. Immunohistochemistry represents the main technique for assessing PD-L1 expression on tumor cells. This review aims to describe the current knowledge of PD-L1 expression in various types of lymphomas, focusing on the principal mechanisms underlying PD-L1 overexpression, its prognostic significance and practical issues concerning the evaluation of PD-L1 immunohistochemical results in lymphomas.

Secondary multicentric large B-cell lymphoma development after intestinal large T-cell lymphoma in a dog

Secondary multicentric large B-cell lymphoma development after intestinal large T-cell lymphoma in a dog

Primary cutaneous anaplastic large T-cell lymphoma: From a lesion peculiar to its diagnosis

The authors present a clinical case of a 42-year-old woman presented to the Emergency Department for a non-pruritic skin lesion in the left lower limb with a few months of evolution.

Synchronous anaplastic large T-cell lymphoma of the eyelid

Synchronous anaplastic large T-cell lymphoma of the eyelid

Implant-associated anaplastic large T-cell lymphoma (BIA-ALCL): case report

Implant-associated anaplastic large T-cell lymphoma (BIA-ALCL): case report

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Epidemiology, Clinical Features and Outcomes of Peripheral T-Cell Lymphoma in Latin America

INTRODUCTION: Peripheral T-cell lymphomas (PTCL) represent a rare and heterogenous group of mature T-cell lymphomas often characterized by aggressive behavior. Previous studies evaluating the distribution of PTCL subtypes across Latin America (LATAM) were limited in their representation of most countries in the region. Additionally, a lack of standardized management for several subtypes and the absence of comprehensive lymphoma registries in LATAM suggests exploring real-world treatment patterns and clinical outcomes. We conducted an international pooled analysis to assess the distribution of PTCL across LATAM countries and report treatment outcomes. METHODS: We compiled data from patients aged ≥18 years with newly diagnosed PTCL from the retrospective registry of the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL, n=988, 1975-2023), the Brazilian T-cell Project (Brazilian TCP, 2015-2017, 168 cases retrospective; 2017-2023, 425 cases prospective) and the prospective registry of the International T cell Project (ITCP, n=529, 2006-2023). Data were abstracted from medical records in a standardized form. Survival data was only available from the GELL and Brazilian TCP. Overall survival (OS) was estimated from diagnosis to death from any cause, while progression-free survival (PFS) was defined from diagnosis to relapse, progression, or death from any cause. We used the Kaplan-Meier method and Log-rank test to estimate and compare survival probabilities. RESULTS: We enrolled 2110 patients from 11 LATAM countries. Overall, the median age at diagnosis was 54 years (range 18-95 years), most were male (59%), present with advanced stage disease (Ann Arbor III-IV, 67%), and had good performance status (ECOG ≤1, 71%) (Table 1). After PTCL not otherwise specified (NOS, 39%), adult T-cell leukemia/lymphoma (ATL, 18%) and extranodal NK/T cell lymphoma (ENKTL, 16%) were the most frequently diagnosed PTCL subtypes with varying distribution across LATAM countries. Peru had a higher prevalence of ATL (39%) and ENKTL was frequently diagnosed in Central America (43%). In contrast, ALK-negative (ALK-) anaplastic large T-cell lymphoma (ALCL) was the second more frequent subtype in Brazil (18%), Chile (16%), and Argentina (9%). The percentage of mature T-cell NOS was 27% in Argentina and 28% in Chile. A total of 1620 received chemotherapy. First-line chemotherapy varied across subtypes. Patients with ENKTL were frequently treated with asparaginase/platinum-based therapy (62%), while CHOP was more commonly used for ATL or PTCL NOS (46% for both). Chemotherapy with CHOEP/EPOCH was frequent for patients with ALK- ALCL (45%), ALK+ (ALCL 47%), or AITL (48%). With a median follow-up of 33 months, the 3-year OS and PFS for the overall cohort were 40% and 30%, respectively. ALK+ ALCL had superior survival estimates, with a 3-year OS of 77% and a 3-year PFS of 73%. The 3-year OS for patients with ENKTL was 48% and the PFS was 45%. Patients with ATL experienced the lowest survival rates (OS and PFS of 23% and 16% at 3 years, respectively). The use of asparaginase/platinum or CHOP-based therapy was associated with superior 3-year OS (61% and 52%, respectively; p=0.011) and PFS (57% and 49%, respectively; p=0.017) among patients with ENKTL. For ATL, the use of CHOEP/EPOCH was associated with improved 3-year OS (21%, p=0.009) and PFS (15%, p=0.024), but outcomes remained dismal. CONCLUSION: To our knowledge, we report the largest pooled cohort of PTCL subtypes across LATAM by leveraging the retrospective registry of the GELL consortium and data from the Brazilian TCP and ITCP. Our findings suggest a distinct distribution of PTCL subtypes across LATAM countries, with a higher prevalence of ATL and ENKTL compared to the epidemiological patterns in Western countries. This distribution underscores a unique opportunity to increase trial enrollment and accrual of rarer PTCL subtypes. The relatively high percentage of mature T-cell NOS suggests difficulties in providing specific lymphoma diagnoses in the region. The low survival rates for some subtypes indicate the need to develop novel therapies to improve patient outcomes. A larger prospective assessment of PTCL epidemiology and treatment outcomes is being planned to expand the ascertainment of cases, improve pathological classification of the different PTCL subtypes, and validate our results in the LATAM region.

T-cell lymphoma involving the rectum of a dog

A mediastinal mass was diagnosed in a 7-year-4-month-old neutered female mixed breed dog following a 3-week history of lethargy, hyporexia and pyrexia. Bi-cavitary imaging, needle aspirate cytology and flow cytometry confirmed WHO clinical stage IVb, intermediate to large T-cell lymphoma involving the mediastinum, liver and spleen. The dog initially responded to a multidrug chemotherapy protocol but clinical deterioration occurred 3 months later. The dog presented with anorexia, vomiting and diarrhoea, associated with marked faecal tenesmus and haematochezia, initially believed by the primary care practitioner to be related to chemotherapy toxicity. However, rectal examination revealed multiple sessile and pedunculated masses. Further diagnostic imaging, cytology and flow cytometry confirmed progressive disease, including T-cell lymphoma of the rectum. Histology and immunohistochemistry confirmed an infiltrate of intermediate-sized CD3-positive neoplastic cells that expanded the rectal mucosa. Rectal lymphoma is uncommon in dogs and previous cases have been B cell in origin. In this report we describe the clinical presentation and macro- and microscopic findings of a case of canine T-cell lymphoma involving the rectum.

Characterization of CD3+/CD20+ canine large-cell lymphoma.

Immunophenotyping of canine large-cell lymphoma (LCL) for B-cell and T-cell surface antigens is commonly performed to better predict the clinical outcome. Expression of surface antigen CD3 is associated with T-cell malignancies; surface antigen CD20 is expressed on B cells. However, a small subset of canine LCLs expresses both CD3 and CD20 (CD3+/CD20+); this form of lymphoma remains poorly defined at the molecular level. In a retrospective study, we aimed to better characterize immunophenotypic properties and antigen receptor clonality of CD3+/CD20+ LCL. We selected formalin-fixed, paraffin-embedded tissues from 10 cases of CD3+/CD20+ LCL and breed-matched controls of peripheral large T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL). Using PCR for antigen receptor rearrangement (PARR), we identified monoclonal T-cell receptor gamma (TCRγ) rearrangements in all CD3+/CD20+ cases. Three of 10 cases had monoclonal rearrangements in the immunoglobulin heavy chain (IgH), supportive of cross-lineage rearrangement. There was no significant difference in the frequency of antigen receptor rearrangement between CD3+/CD20+ and PTCL cases. In comparison with DLBCL, CD3+/CD20+ LCL had TCRγ rearrangement more frequently and IgH rearrangement less frequently, respectively. Immunolabeling of the B-cell marker PAX5 occurred less frequently in all CD3+/CD20+ LCL cases compared to the DLBCL controls. Immunolabeling for BCL-2 was robust, regardless of immunophenotype. Nuclear Ki67 positivity was variable in CD3+/CD20+ cases, indicating a heterogeneity in proliferation. Overall, cases of canine CD3+/CD20+ LCL had properties similar to PTCL, suggesting a similar histogenesis of these 2 subsets.

Coexistence of ALK-negative anaplastic large T-cell lymphoma and plasmablastic lymphoma in the same patient: A case report

Alk-negative anaplastic lymphoma and plasmablastic lymphoma are both rare lymphoid neoplasms, and usually have poor prognosis. We present the case of a patient who was diagnosed with both diseases within a short time from each other.

Primary breast lymphoma: a case series and review of the literature

BackgroundPrimary breast lymphoma (PBL) is a very rare form of non-Hodgkin's lymphoma (NHL), defined as a malignant primary lymphoma occurring in the breast in the absence of previously detected lymphoma localizations. Our study aims to retrospectively evaluate the epidemiological, clinical, and imaging findings and therapeutic features of breast lymphomas in patients with primary lymphoma of the breast.Materials and methodsThis is a retrospective study including 13 patients with primary non-Hodgkin's lymphoma of the breast treated at the Salah Azaiez Institute of Oncology from 2000 to 2019. This sample includes 1 case of follicular lymphoma, 2 cases of large T-cell lymphoma, and 10 cases of large B-cell lymphoma.ResultsPatients included in the study were aged between 17 and 89 years (average age of 52.6 years). All patients were referred because of a lump in the breast, and only one patient consulted with inflammatory signs in the breast. The average clinical size of the tumor was 7.2 cm, with a maximum of 15 cm. Mammography showed an oval mass with circumscribed margins in the majority of cases. Ultrasound showed in most cases a hypoechoic irregular mass or multilobulated mass with irregular margins and hypervascular on color Doppler. Magnetic resonance imaging (MRI) was performed on only three patients and showed a spiculated lesion with polycyclic limits. Eight patients underwent surgery. In our study breast lymphomas involved 10 cases of large B-cell lymphoma, one case of follicular lymphoma, and two cases of large T-cell lymphoma. In this series, 11 patients had localized stages (I + II) at diagnosis, and 2 patients had disseminated stages (stage III) of primary breast lymphoma. Seven patients underwent chemotherapy treatment alone, and five had chemotherapy with radiotherapy. The median follow-up of our patients was 53 months, ranging from 1 to 177 months. Overall survival was 71% at 3 years and 51% at 5 years.ConclusionPrimary breast lymphoma is an uncommon type of breast malignancy. The optimal treatment modality is still in question because of the rarity of this disease. However, the use of combination therapy produces the most favorable results. Surgery is not yet recommended.

Phosphorylated STAT3 as a potential diagnostic and predictive biomarker in ALK- ALCL vs. CD30high PTCL, NOS.

The differential diagnosis between ALK-negative anaplastic large cell lymphoma (ALK- ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with high expression of CD30 (CD30high) are essential. However, no reliable biomarker is available in daily practice except CD30. STAT3 is characteristically activated in ALCL. We aimed to investigate whether the status of STAT3 phosphorylation could help the differential diagnosis. The status of phosphorylation of STAT3 was examined using two antibodies against pSTAT3-Y705 and pSTAT3-S727 by immunohistochemistry in ALK+ ALCL (n=33), ALK- ALCL (n=22) and PTCL, NOS (n=34). Ten PTCL, NOS with diffuse CD30 expression were defined as CD30high PTCL, NOS. Flowcytometric analysis were performed to evaluate the expression of pSTAT3-Y705/S727 in PTCL, NOS (n=3). The median H-scores of pSTAT3-Y705 and S727 were 280 and 260 in ALK+ ALCL, 250 and 240 in ALK- ALCL, and 45 and 75 in CD30high subgroup, respectively. Using H score of 145 as the cutoff value, pSTAT3-S727 alone distinguished between ALK- ALCL and CD30high PTCL, NOS with a sensitivity of 100% and specificity of 83%. Additionally, pSTAT3-S727, but not pSTAT3-Y705, was also expressed by background tumor-infiltrating lymphocytes (S727TILs) in PTCL, NOS. PTCL, NOS patients with high S727TILs H score had a favorable prognosis than those with no TILs (3-year OS rate: 43% vs. 0, p=0.013) or low S727TILs (3-year OS rate: 43% vs. 0, p=0.099). Flowcytometric analysis revealed that of the three patients investigated, two had enhanced pSTAT-S727 signals in neoplastic cell populations, and all three patients were negative for pSTAT3-Y705 expression in both tumor cells and background lymphocytes. pSTAT3-Y705/S727 can be used to help distinguish ALK- ALCL from CD30high PTCL, NOS and pSTAT3-S727 expression by TILs predicts the prognosis of a subset of PTCL, NOS.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: The Nordic Lymphoma Group (NLG) performed a dose-finding/expansion trial evaluating pixantrone, etoposide, bendamustine and, in CD20+ lymphomas, rituximab (P[R]EBEN) in patients (pts) with relapsed diffuse large B-cell (DLBCL) or peripheral T-cell (PTCL) lymphomas. The regimen was out-patient based, and applicable in frail, heavily pre-treated pts. Here we present a long-term follow-up of the trial and a per-protocol correlative biological analysis of pre-therapeutic tumour biopsies looking for gene expression profiles associated with long-term response. Methods: We enrolled 60 pts (37 DLBCL and 23 PTCL; age range: 39–84 yrs, median: 71 yrs). Time to event parameters were analyzed by Kaplan-Meier estimates, log-rank test and Cox regression models. Pre-therapeutic biopsies from 42 pts (25 DLBCL, 17 PTCL) were analyzed for gene expression by NanoString PanCancer Pathways and Immune profiling panels (altogether 1348 genes). Results: Of the original 60 patients, 22 were alive at the time of the present analysis. The median follow-up of surviving pts was 41 mo (range 26–76 mo). The 38 deaths were due to: lymphoma (24; 63%), infections (3; 8%) and other causes (11; 29%: 1 lung carcinoma, 5 acute myeloid leukemia-AML, 1 myelodysplasia-MDS, 1 lung embolism, 1 allotransplant related and 2 unknown). Of the 6 pts with AML/MDS, 5 were PTCL and 1 DLBCL. Of 58 evaluable pts, 38 (65%) had a complete (CR) and 1 (3%) a partial response (B: 51%; T: 70%). The median duration of response (DoR) of the 38 CR pts was 17 mo (range 0.5–55 mo; B: 18 mo; T: 17 mo). Four pts were bridged to allogeneic transplant. The overall 5-yr OS and PFS were 33% and 19%, respectively. The median OS for DLBCL was 16.0 mo [IQR 7.0>] and for PTCL 18.0 mo [IQR 8.0>]. The median PFS for DLBCL was 10.0 mo [IQR 4.0–32.0] and for PTCL 10.0 mo [IQR 5.0–26.0]. To better understand molecular alterations underlying the delay of relapse in this heavily pre-treated elderly population, we determined differentially expressed genes between short (<12 mo) and long term (>12 mo) responders. In DLBCL, 31 genes showed significant differential expression between short- and long-term responders (P < 0.05). The latter had higher expression of genes related to transcription factor activity. The gene most significantly associated with long-term response was Neutrophil Cytosolic Factor 4 (NCF4). In PTCL, 23 genes were differentially expressed between short- and long-term responders, the latter showing enrichment in Ras signaling pathway genes (e.g., Rac Family Small GTPase 3, RAC3, and phospholipase A2 group IIA, PLA2G2A). The research was funded by: Servier Laboratoires Keywords: Aggressive B-cell non-Hodgkin lymphoma, Aggressive T-cell non-Hodgkin lymphoma, Combination Therapies No conflicts of interests pertinent to the abstract.

Breast Implant-Associated Tumors.

In addition to anaplastic large T-cell lymphomas (BIA-ALCL), other implant-related tumors have been described for some years. Squamous cell carcinoma (SSC) and B-cell lymphomas occurred in very rare cases. The unexplained pathogenesis as well as the unclear individual risk profile is an ongoing source of uncertainty for patients and physicians. The pathogenesis of the tumors is still largely not understood. While BIA-ALCL occurs more frequently with textured breast implants, other tumors were also observed with smooth implants and at other implant sites. Multiple potential mechanisms are discussed. It is suspected that the etiology of a chronic inflammatory response and subsequently immunostimulation is multifactorial and appears to play a key role in the malignant transformation. Since there are currently no sufficiently valid data for a specific risk assessment, this must be done with caution. This article presents the incidence, pathogenesis, as well as the level of evidence according to the current state of knowledge, and evaluates and discusses the current literature.

Abstract 5233: Germline CHEK2 variants and risk of lymphoma

Abstract Lymphoma is the sixth most commonly diagnosed cancer in the US. Genome-wide association studies have identified common variants associated with risk of specific lymphoma subtypes, but less is known about the contribution of rare inherited variants in the genetic architecture of lymphoma risk. CHEK2 is important to DNA repair and 2 small studies have found evidence of an association between CHEK2 variants and risk of lymphoma. Here, we investigated loss of function (LoF) variants in CHEK2 with risk of lymphoma (overall and subtypes). The study population included newly diagnosed lymphoma cases from Mayo who were enrolled in the Lymphoma SPORE Molecular Epidemiology Resource (MER). Controls were from the Mayo Clinic Biobank, from which we excluded a prior hematologic malignancy. Whole exome sequencing was performed by Regeneron on an Illumina NovaSeq panel (mean coverage of 48X). Variants were called using GATK v4 and variant annotation was performed using BioR. All LoF variants (nonsense, frameshift and consensus splice sites) in CHEK2 with a minor allele frequency &amp;lt; 0.5% were included in the analyses. Logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (CI) for the association between CHEK2mutation status and risk of lymphoma overall, and by lymphoma subtypes that had more than 5 mutation carriers, which included diffuse large B-cell (DLBCL), follicular (FL), and T-cell lymphoma (TCL). All analyses were adjusted for age (at diagnosis for cases and at enrollment for controls) and sex. A total of 4,852 lymphoma cases and 49,724 controls were included in this analysis. Median age for both cases and controls was 62 years (range 18-99 years). Males accounted for 57.5% (n=2,789) of the cases and 40.6% (n=20,186) of the controls. The DLBCL (23.6% of cases) and FL (23.3% of cases) subtypes were the most common; 7.6% of cases had TCL. A total of 407 (0.7%) individuals had a LoF variant. The frequency of LoF variants was 1.2% in lymphoma cases and 0.7% in controls. LoF variants were associated with increased risk of lymphoma overall (OR=1.77; 95%CI: 1.32-2.33), DLBCL (OR=2.07; 95%CI: 1.20-3.13), and TCL (OR=2.78; 95%CI: 1.178-5.50), but not FL (OR=1.31; 95%CI: 0.65-2.34). CHEK2 c.1100delC was the most frequently mutated variant in this population, accounting for 76% of all LoF variants. Individuals with a c.1100delC variant had an increased risk of lymphoma overall (OR=1.90; 95%CI: 1.37-2.58), DLBCL (OR=2.06; 95%CI: 1.09-3.54), and TCL (OR=3.17; 95%CI:1.24-6.58), but not FL (OR=1.05; 95%CI: 0.41-2.15). When restricted to cases, there was no significant difference in age at diagnosis (P=0.62) or sex (P=0.53) between LoF variant carriers and non-carriers. In this large lymphoma case-control study, CHEK2 LoF variants were associated with increased risk of lymphoma, demonstrating that rare inherited variants may play an important role in the etiology of lymphoma. Additional work is needed to investigate missense variants in CHEK2 and risk of lymphoma. Citation Format: Nicholas J. Boddicker, Raphael Mwangi, Dennis P. Robinson, Allison C. Rosenthal, Thomas M. Habermann, Andrew L. Feldman, Lisa M. Rimsza, Rebecca L. King, Melissa C. Larson, Brianna J. Gysbers, Stephen M. Ansell, Jithma P. Abeykoon, Grzegorz S. Nowakowski, Thomas E. Witzig, Anne J. Novak, Susan L. Slager, James R. Cerhan. Germline CHEK2 variants and risk of lymphoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5233.

Cutaneous anaplastic large T-cell lymphoma in a cat - case report

Cutaneous anaplastic large T-cell lymphoma in a cat - case report

Thirty Years of Experience With Ocular Adnexal T-Cell Lymphoma.

To evaluate the disease characteristics and survival of patients with ocular adnexal T-cell lymphoma. A retrospective, observational study of patients with a histopathological diagnosis of T-cell lymphoma of the ocular adnexa seen between 1992 and 2022. Demographic data, clinical presentation, imaging, histology, immunohistochemistry, treatment, and outcomes were reviewed. Fifteen patients were included in the study with the mean age at diagnosis of 50 years old (range 7-85). The most common presenting symptoms were ulcerated eyelid skin lesions (40%) followed by eyelid swelling (13.3%), and lacrimal passageways obstruction (13.3%). The anaplastic large cell lymphoma (33%) and primary cutaneous T-cell lymphoma (33%) were the most diagnosed peripheral T-cell lymphoma subtypes, followed by the nasal type natural killer/T-cell lymphoma (27%) and peripheral T-cell lymphoma not otherwise specified (7%). The most prevalent stage of disease progression was stage I and stage IV (Ann Arbor classification) with seven (47%) patients each. Eight (53%) patients succumbed to the disease process of which three (37.5%) deceased in the first six months and six (75%) within the first year of diagnosis. We identified a strong statistical association between stage and disease-related death ( p = 0.003). Peripheral T-cell lymphoma occurring in the orbit and ocular adnexa is extremely rare. Advanced stage at diagnosis leads to almost certain death from the disease despite aggressive local and systemic treatment. Early diagnosis improves the chances of survival but can be hindered by this condition's ability to simulate benign inflammatory conditions both clinically and histologically.

Predictive value of topoisomerase IIα immunoreactivity in canine diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) treated with a doxorubicin-based chemotherapy protocol

Topoisomerase IIα (TOPIIα) plays a key role in DNA replication and is a molecular target for TOPIIα inhibitor chemotherapy. A doxorubicin-based chemotherapy remains the most effective treatment for canine lymphoma, but there are no clear indications for its use in individual patients. The aim of this study was to assess the predictive value of TOPIIα expression in the treatment of canine lymphomas with TOPIIα inhibitors. Samples of formalin-fixed paraffin-embedded lymph nodes from 14 dogs with diffuse large B-cell lymphoma (DLBCL) and 5 dogs with peripheral T-cell lymphoma (PTCL) treated with a CHOP protocol were immunohistochemically labelled with anti-TOPIIα. Progression-free survival time (PFS) and overall survival time (OS) were estimated and compared with TOPIIα expression. Dogs with DLBCL had a higher level of TOPIIα expression compared to dogs with PTCL. The median PFS for dogs with DLBCL was significantly longer (260 days) than it was for dogs with PTCL (60 days). In DLBCL dogs with a high TOPIIα expression level, the median PFS was significantly longer (310 days) then it was in dogs with week or medium TOPIIα expression (51 days). The results of the study indicate that the immunohistochemical assessment of TOPIIα expression may be a valuable predictive indicator for anthracycline-based treatment of dogs with malignant lymphoma.

Outcome of limited-stage peripheral T-Cell lymphoma after CHOP(-like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group.

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 6-8cycles of CHOP(-like) therapy and 22% received 3-4cycles, 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 (3-4cycles vs. 6-8cycles 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 3-4cycles versus 6-8cycles of CHOP(-like) therapy were comparable.