Therapeutic challenges in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.

Dependence of peripheral T-cell lymphoma on constitutively activated JAK3: Implication for JAK3 inhibition as a therapeutic approach.

Peripheral T-cell lymphoma (PTCL) is a clinically heterogeneous group that represents 10%-15% of all lymphomas. Despite improved genetic and molecular understanding, treatment outcomes for PTCL have not shown significant improvement. Although Janus kinase-2 (JAK2) plays an important role in myeloproliferative neoplasms, the critical role of JAK isoforms in mediating prosurvival signaling in PTCL cells is not well defined. Immunohistochemical analysis of PTCL tumors (n = 96) revealed high levels of constitutively active JAK3 (pJAK3) that significantly (p < 0.04) correlated with the activation state of its canonical substrate STAT3. Furthermore, constitutive activation of JAK3 and STAT3 positively correlated, at least in part, with an oncogenic tyrosine phosphatase PTPN11. Pharmacological inhibition of JAK3 but not JAK1/JAK2 significantly (p < 0.001) decreased PTCL proliferation, survival and STAT3 activation. A sharp contrast was observed in the pJAK3 positivity between ALK+ (85.7%) versus ALK-negative (10.0%) in human PTCL tumors and PTCL cell lines. Moreover, JAK3 and ALK reciprocally interacted in PTCL cells, forming a complex to possibly regulate STAT3 signaling. Finally, combined inhibition of JAK3 (by WHI-P154) and ALK (by crizotinib or alectinib) significantly (p < 0.01) decreased the survival of PTCL cells as compared to either agent alone by inhibiting STAT3 downstream signaling. Collectively, our findings establish that JAK3 is a therapeutic target for a subset of PTCL, and provide rationale for the clinical evaluation of JAK3 inhibitors combined with ALK-targeted therapy in PTCL.

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.

The Role of Epigenetic Modifier Mutations in Peripheral T-Cell Lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a group of diseases with a low incidence, high degree of heterogeneity, and a dismal prognosis in most cases. Because of the low incidence of these diseases, there have been few therapeutic novelties developed over time. Nevertheless, this fact is changing presently as epigenetic modifiers have been shown to be recurrently mutated in some types of PTCLs, especially in the cases of PTCLs not otherwise specified (PTCL-NOS), T follicular helper (TFH), and angioimmunoblastic T-cell lymphoma (AITL). These have brought about more insight into PTCL biology, especially in the case of PTCLs arising from TFH lymphocytes. From a biological perspective, it has been observed that ten-eleven translocators (TET2) mutated T lymphocytes tend to polarize to TFH, while Tregs lose their inhibitory properties. IDH2 R172 was shown to have inhibitory effects on TET2, mimicking the effects of TET2 mutations, as well as having effects on histone methylation. DNA methyltransferase 3A (DNMT3A) loss-of-function, although it was shown to have opposite effects to TET2 from an inflammatory perspective, was also shown to increase the number of T lymphocyte progenitors. Aside from bringing about more knowledge of PTCL biology, these mutations were shown to increase the sensitivity of PTCLs to certain epigenetic therapies, like hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDACis). Thus, to answer the question from the title of this review: We found the Achilles heel, but only for one of the Achilles.

Recent histone deacetylase inhibitors in cancer therapy.

Cancer metastasis increases the complexity of the disease and escalates patient mortality. Traditional chemotherapy has been associated with low efficacy and marked side effects. Studies pivot toward histone deacetylase (HDAC) enzymes and inhibitors because they are critical for chromatin structure, gene regulation, and cellular activities that are linked to metastasis and cancer progression. HDAC inhibitors (HDACi) can alter gene expression patterns and can lead to cell-cycle arrest and apoptosis in neoplastic cells. Several HDACi drugs like vorinostat, romidepsin, panobinostat, and belinostat are approved by the Food and Drug Administration. China and Japan have approved the use of tucidinostat, a new subtype-selective HDACi that inhibits class 1 HDAC1, HDAC2, HDAC3, as well as class 2b HDAC10. These drugs have shown promising results in the treatment of multiple carcinoma including cervical cancer, T-cell lymphoma, brain cancer, and breast cancer. This review highlights the HDACi classes, the mechanism of action of these inhibitors, their preclinical and clinical efficacy, and the latest clinical trials and patents used in cancer therapeutics. Overall, this review focuses on patents and clinical trials data from 2019 onward to give a better viewpoint on current trends in HDACis as chemotherapy agents.

Hematological Oncology journal women in lymphoma special issue: Latest updates in nodal peripheral T-cell lymphoma.

In the last decade, there has been increased understanding of the pathologic features and biology of peripheral T cell lymphomas (PTCLs) through development of multi omics and molecular profiling techniques. In addition, international collaborations through multi center trials as well as prospective registry studies have improved our knowledge of host and tumor genomic factors and treatment factors affecting disease outcomes. In our review today, we aim to highlight the current epidemiology, latest advances in classification, disease biology and the evolving treatment landscape for nodal PTCLs.

Clinical, endoscopic and pathological characteristics of primary gastrointestinal T-cell and NK/T-cell lymphomas.

BACKGROUND AND AIMS: Gastrointestinal T-cell and NK/T-cell lymphomas are relatively rare and may be difficult to diagnose. Therefore, we performed a retrospective study of the clinical, endoscopic and pathological characteristics of these lymphomas, to provide additional data on this issue. METHODS: From April 2013 to April 2021, consecutive patients diagnosed with primary gastrointestinal T-cell and NK/T-cell lymphomas were retrospectively reviewed. Their medical histories, laboratory, imaging, endoscopic, and pathology results were analyzed. RESULTS: Forty-two patients were finally chosen, among whom, 24 patients had ENKTCL, 9 patients had MEITL, 2 patients had ALCL, ALK-, 1 patient had ALCL, ALK+, and 6 patients had PTCL, NOS. The median age of all the patients was 48 years old, and 73.81% (31 patients) were male. The patients' symptoms were abdominal pain, diarrhea, gastrointestinal bleeding, weight loss, fever, and others. The endoscopic results of 26 patients could be traced, and 69.23% of the patients showed multiple lesions. Ulcerative and ulceroinfiltrative lesions were common. Among the pathologic findings, necrosis, ulceration, and crypt atrophy were commonly found while epitheliotropism was relatively less common. Twelve patients (28.57%) had a history of misdiagnosis. After a median follow-up time of 26.9 months, 26 patients (66.70%) died of the disease. The median overall survival time was 8 months. CONCLUSIONS: These lymphomas had nonspecific clinical manifestations, various endoscopic features, and were likely to be misdiagnosed as other diseases. The prognosis is still poor, and more in-depth research is needed to develop more precise treatments.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Phase 1 trial of carfilzomib in relapsed/refractory peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

Management of Peripheral T-cell Lymphomas and the Role of Transplant.

PURPOSE OF REVIEW: Here, we review the management of peripheral T-cell lymphoma, particularly focusing on the role of autologous and allogeneic stem cell transplant. RECENT FINDINGS: Peripheral T-cell lymphomas are a rare subset of non-Hodgkin's lymphomas that are treated with curative intent. While therapy has been based on other aggressive lymphoid malignancies, outcomes are generally poorer than B-cell lymphomas with 5-year overall and progression-free survival of 30-40% and 20-30%, respectively. In effort to improve outcomes, transplant has been used in both the frontline and salvage settings. Although not studied in randomized studies, consolidation with autologous stem cell transplant in first remission has been associated with an approximate 5-year overall survival of 50-60% and 5-year progression-free survival of 40-45%. Unfortunately, most patients relapse, and, in this setting, allogeneic transplant remains the only curative option for those who are transplant-eligible. Multiple series have now shown that 3-year overall survival with allogeneic transplant is approximately 60%. However, outcomes with transplant are associated with disease control at the time of transplant. In contrast to B-cell malignancies, treatment decisions for peripheral T-cell lymphomas are supported mostly by phase II studies, retrospective series, and expert opinion. For patients with peripheral T-cell lymphoma able to achieve sufficient disease control, autologous stem cell transplantation in first remission and allogeneic stem cell transplantation in relapsed disease offer modest benefit over chemotherapy alone.

Diagnosis, management and follow up of peripheral T-cell lymphomas: a consensus practice statement from the Australasian Lymphoma Alliance.

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous disease group accounting for 10% of non-Hodgkin lymphomas. PTCL patients have typically poorer outcomes compared with aggressive B-cell lymphomas. However, such outcomes are heavily dependent on subtype. Although anthracycline-based regimens such as cyclophosphamide, doxorubicin, vincristine and prednisone remain the standard first-line treatment for most aggressive PTCL, there are important variations including incorporation of novel agents, use of radiotherapy and judicious consideration of stem cell transplantation. Relapsed or refractory disease represents a significant area of unmet need where chemotherapy intensification has limited efficacy and novel agents such as brentuximab vedotin and pralatrexate provide additional opportunities for attainment of remission and potential stem cell transplant. In the future, pre-therapy prognostic biomarkers including genomic characterisation, may aid in risk stratification and help guide initial patient management to improve survival. There is an urgent need to understand better the pathogenesis of PTCL to facilitate novel drug combinatorial approaches to improve survival. This position statement represents an evidence-based synthesis of the literature for application in Australian and New Zealand practice.

[Pathogenesis and therapeutic advances of peripheral T-cell lymphoma].

According to the recently revised WHO classification, peripheral T-cell lymphomas (PTCL) can be classified into up to 30 subtypes. Because the majority of these subtypes were rare cancers, their pathophysiology was not well understood. However, technological advancements including multi-omics approaches such as genomic and gene expression analyses have made significant progress in understanding the pathophysiology of PTCL. Based on the results of these basic studies, the classification of T-cell lymphomas has been changed. Furthermore, new markers discovered through genomic analysis and gene expression analysis are being incorporated into the diagnostic processes of PTCL. Furthermore, multiple new drugs were approved to treat patients of PTCL. Clinical trials are also being carried out as first-line treatments to test the efficacy to combine these new drugs with conventional treatments.

[Genetic alterations in new category of Peripheral T-cell lymphoma, not otherwise specified].

Peripheral T-cell lymphomas (PTCLs) are mature T-cell and natural killer (NK) cell neoplasms with poor prognosis and no available standard treatment. The 2016 revision of the World Health Organization classification of hematological malignancies recognized a new group of nodal T-cell lymphoma with T follicular helper cell phenotype due to the presence of a group of PTCLs, not otherwise specified. This new subgroup of tumors showed clinical and molecular similarities with angioimmunoblastic T-cell lymphoma (AITL). AITL patients have mutations in the Vav guanine nucleotide exchange factor-1 (VAV1) gene. We established a transgenic mouse model harboring VAV1 gene mutation. These mice developed tumors that mimic human T-lymphoblastic lymphoma and the newly proposed PTCL-GATA3 subtype. To develop personalized treatment strategies by analyzing subgroup-specific mouse models, our study supports the establishment of PTCL subgroups based on genetic alterations or gene expression profiles.

Molecular features of non-anaplastic peripheral T-cell lymphoma in children and adolescents.

Non-anaplasticperipheral T-cell lymphomas (PTCL) are rare tumors in children, adolescents, and young adults (CAYA) with poor prognosis and scarce genetic data. We analyzed lymphoma tissue from 36 patients up to 18 years old with PTCL, not otherwise specified (PTCL-NOS), hepatosplenic T-cell lymphoma, Epstein-Barr virus (EBV)-positive T-lymphoproliferative diseases, subcutaneous panniculitis-like T-cell lymphoma, and other PTCL types. Twenty-three patients (64%) had at least one genetic variant detectable, including TET2, KMT2C, PIK3D, and DMNT3A. TP53 and RHOA variants, commonly found in adults, were not identified. Eight of 20 (40%) CAYA PTCL-NOS had no detectable mutations. The genetic findings suggest that CAYA PTCL differ from adult cases.

The role of pre-treatment and mid-treatment 18F-FDG PET/CT imaging in evaluating prognosis of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).

BACKGROUND: It has been reported the prognostic value of MTV in predicting the disease prognosis of peripheral T-cell lymphoma (PTCL) through pre-treatment PET/CT imaging. However, these are limited data on pretreatment evaluation and prognosis assessments of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). This study aimed to determine the prognostic values of pre-treatment and mid-treatment total metabolic tumor volume (MTV), total lesion glycolysis (TLG), and Deauville 5-Point Scale (D-5PS) in accessing the prognosis of PTCL-NOS. METHODS: A retrospective analysis was conducted in 31 patients with pathologically diagnosed PTCL-NOS. These patients have undergone positron emission PET/CT scanning before and during chemotherapy. Follow-ups were also done to investigate the 2-year progression-free survival (PFS) and Overall Survival (OS) of these patients. During [Formula: see text]F-fluorodeoxyglucose ([Formula: see text]F-FDG) PET/CT scans, the MTV and TLG were recorded. Meanwhile, [Formula: see text]MTV and [Formula: see text]TLG were calculated. Furthermore, the receiver operating characteristic (ROC) curve was employed to classify and to define the threshold values. On the other hand, the mid-chemotherapy assessment and staging of these 31 patients were done by utilizing D-5PS. Subsequently, based on the D-5PS scores obtained, these patients were grouped into two categories: a group of patients with a score of <4 and another group with [Formula: see text]4 points. For these two groups of patients, the survival analysis was done by Kaplan-Meier analysis and a multivariate COX regression model. Moreover, Pearson's chi-square test ([Formula: see text] test) and Spearman rank correlation coefficient were used to comparing the collected data, respectively. RESULTS: During the 2-year follow-up period, 15 out of the 31 patients experienced disease progression. The optimal threshold values for both baseline MTV and TLG were 158.16 cm[Formula: see text] and 677.40.Additionally, the difference in 2-year PFS between the progressive and non-progressive groups was statistically significant ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text]), significant between-group difference was detected for MTV and for TLG ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text]). On the other hand, when these patients were classified into two groups according to the mid-chemotherapy Deauville score of <4 and [Formula: see text]4, the statistical difference of 2-year PFS between these two groups was significant, too ([Formula: see text], [Formula: see text]),but there is no significant between-group difference in OS ([Formula: see text], [Formula: see text]). COX analysis revealed that D-5PS are the independent factors influencing PFS, while MTV is the independent influencing factor of OS. CONCLUSION: The baseline total MTV obtained by PET/CT scanning, and D-5PS are crucial prognostic factors in evaluating the prognosis of PTCL-NOS.

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma.

INTRODUCTION: Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. METHOD: This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. RESULTS: Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. CONCLUSION: Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

[Two-year remission of a relapsed primary gastric peripheral T-cell lymphoma treated with total gastrectomy followed by adjuvant chemotherapy].

A 67-year-old man was diagnosed with a submucosal primary gastric T-cell lymphoma (PGTL) via upper gastroenteroscopy following an annual health check-up. He received six cycles of CHOP and achieved a complete remission. However, the patient relapsed 4 months post therapy. A second remission, which was maintained for years, was achieved after surgical gastrectomy followed by adjuvant chemotherapies. Prior reports have shown that surgery combined with chemotherapies was curative for patients with newly-diagnosed PGTL. In this report, surgery combined with chemotherapies was successfully applied for early-relapsed PGTL.

Chidamide combined with cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with peripheral T-cell lymphoma.

OBJECTIVE: Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). This phase 1b study evaluated the safety, pharmacokinetics, and preliminary efficacy of chidamide in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for treatment-naïve PTCL patients. METHODS: This study was an open-label, multicenter trial composed of dose escalation and dose expansion. Patients received CHOP for six 21-d cycles and chidamide on d 1, 4, 8 and 11 in each cycle. Four dose levels of chidamide (20, 25, 30 and 35 mg) were evaluated. The primary objective was to evaluate the safety and tolerability of the combination regimen. RESULTS: A total of 30 patients were evaluated in this study: 15 in the dose-escalation part and 15 in the dose-expansion part. In the dose-escalation study, three patients were enrolled in the 35 mg chidamide cohort. One had dose-limiting toxicity with grade 3 vascular access complications, and one had grade 2 neutropenia with a sustained temperature >38 °C. Dose escalation was stopped at this chidamide dose level. The most common (≥10%) grade 3 or 4 adverse events (AEs) were leukopenia (90.0%), neutropenia (83.3%), vomiting (13.3%), thrombocytopenia (10.0%) and febrile neutropenia (10.0%). No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment. The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3% (25/28), with 16 (57.1%) achieving complete response or unconfirmed complete response. The estimated median progression-free survival was 14.0 months. In summary, we chose chidamide 30 mg as the recommended dose for phase 2. CONCLUSIONS: The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients, which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.

GATA-3 in T-cell lymphoproliferative disorders.

GATA-3 regulates the differentiation, proliferation, survival, and function of peripheral T cells and their thymic progenitors. Recent findings, reviewed here, not only implicate GATA-3 in the pathogenesis of molecularly, genetically, and clinically distinct T-cell lymphoproliferative disorders, but also have significant diagnostic, prognostic, and therapeutic implications.

Treatment with brentuximab vedotin plus bendamustine in unselected patients with CD30-positive aggressive lymphomas.

OBJECTIVES: A treatment regimen consisting of bendamustine and brentuximab vedotin (BV) has been described as a highly potent salvage therapy and as an effective induction therapy leading to high response rates before autologous stem cell transplantation (ASCT) in patients with classical Hodgkin lymphoma (cHL). In this retrospective analysis, we aimed to assess this therapy's efficacy in unselected patients with cHL and CD30+ peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Data of 28 patients with cHL and five patients with PTCL treated with a combination of bendamustine and BV at three Austrian tertiary cancer centers were analyzed. RESULTS: In patients with cHL, the ORR was 100% (78.6% CR, 21.4% PR). After 17 months median follow-up, median survival times were not reached; 1-year PFS was 81.9%, and 1-year OS was 95.7%. Thirteen eligible patients (46.4%) successfully underwent planned ASCT after salvage therapy with bendamustine and BV and subsequent high-dose chemotherapy. Three of the five PTCL patients achieved CR, while two did not respond and died during or shortly after therapy. CONCLUSION: A combination of bendamustine and BV is an effective salvage and induction therapy before ASCT in patients with relapsed/refractory cHL. Further research is warranted to evaluate the use in patients with PTCL.