Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Secondary primary malignancies after CD-19 directed CAR-T-cell therapy in lymphomas: A report from the Italian CART-SIE study.

Secondary primary malignancies (SPM) have been reported after anti-BCMA or anti-CD19 chimeric antigen receptor (CAR)-T-cell therapies. While the cytotoxic effect of antecedent therapies, including chemotherapy and radiotherapy, has been well established, few data are available on risk related to CAR-T immunotherapies. The study aimed to analyse the incidence of SPM in 651 patients enrolled in the Italian prospective observational CART-SIE study. SPMs were documented in 4.3% (28/651), and the most frequent SPMs were haematological malignancies. In conclusion, the frequency of SPMs in our cohort of heavily pretreated patients receiving CAR-T was relatively low and consistent with previous studies.

Real-world outcomes following third or subsequent lines of therapy: A Danish population-based study on 189 patients with relapsed/refractory large B-cell lymphomas.

Outcome data of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) beyond the second line are scarce outside of clinical trials. Novel therapies in the R/R setting have been approved based on single-arm trials, but results need to be contextualized by real-world outcomes. Medical records from 3753 Danish adults diagnosed with DLBCL were reviewed. Patients previously treated with rituximab and anthracycline-based chemotherapy who received the third or later line (3 L+) of treatment after 1 January 2015, were included. Only 189 patients with a median age of 71 years were eligible. The median time since the last line of therapy was 6 months. Patients were treated with either best supportive care (22%), platinum-based salvage therapy (13%), low-intensity chemotherapy (22%), in clinical trial (14%) or various combination treatments (32%). The 2-year OS-/PFS estimates were 25% and 12% for all patients and 49% and 17% for those treated with platinum-based salvage therapy. Age ≥70, CNS involvement, elevated LDH and ECOG ≥2 predicted poor outcomes, and patients with 0-1 of these risk factors had a 2-year OS estimate of 65%. Only a very small fraction of DLBCL patients received third-line treatment and were eligible for inclusion. Outcomes were generally poor, but better in intensively treated, fit young patients with limited disease.

[3D/4D strategic lymph node diagnostics : The 4D representation of the human lymph node enables the observation and interpretation of the immune system in space and time]. / 3D/4D strategische Lymphknotendiagnostik : Die 4D-Darstellung des humanen Lymphknotens ermöglicht die Beobachtung und Interpretation des Immunsystems in Raum und Zeit.

BACKGROUND: Lymph-node diagnostics is performed using thin sections, with help of immunohistochemistry by light microscopy and supplemented by molecular pathology. OBJECTIVES: Which are the scientific and diagnostic perspectives of 3D and 4D lymph node investigations, using laser, scanning, and computer technologies? What is the impact of machine learning in complex data analysis. RESULTS: It was shown in different investigations that the analysis in space and time (3D/4D) of lymph node tissue is able to provide a lot of new information concerning biology and diagnostics and enable excellent evaluations applying machine learning. CONCLUSION OR DISCUSSION: 3D and 4D analysis of human lymphoid tissue gives new insights into immunologic mechanisms and malignant lymphomas.

Final results of a phase II study of CHOEP plus lenalidomide as initial therapy for patients with stage II-IV peripheral T-cell lymphoma.

There remains no one standard induction for nodal-based peripheral T-cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1-10 of a 21-day cycle for six cycles of therapy followed by observation, high-dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference. Among 39 patients evaluable for efficacy, the objective response rate after six cycles was 69%, with complete response in 49%, partial response in 21%, stable disease in 0% and progressive disease in 13%. Thirty-two patients (82%) completed full induction, and seven patients (18%) discontinued for toxicity, primarily hematologic. Any grade hematologic toxicity occurred in over 50% of patients, with grade 3 or 4 febrile neutropenia occurring in 35% of patients despite mandated growth factors. With a median followup of surviving patients of 21.3 months, the estimated 2-year progression-free and overall survival were 55% (95% CI 37%-70%) and 78% (95% CI 59%-89%), respectively. In sum, six cycles of lenalidomide plus CHOEP resulted in a modest response rate primarily due to hematologic toxicity, which prevented all patients from completing planned induction.

Distribution of lymphoma subtypes in Ukraine according to the WHO 2016 classification.

The Ukrainian Lymphoma Registry (ULR) was established in 2019 with the aim of monitoring the quality of diagnosis, staging, and treatment of lymphoma in Ukraine. Between September 2019 and October 2021, 546 patients with newly diagnosed lymphoma were prospectively registered. All cases were diagnosed according to the 2016 updated WHO lymphoma classification. The male-to-female ratio (M/F) for the whole population was 0.7, with a median age of 46 years (range 18-95). The adoption of the 2016 WHO classification resulted in the identification of 36 different lymphoma subtypes, with 132 cases (24.2%) classified differently compared to the 2008 WHO classification. Only 12 cases (2.8%) were true new entities, including seven cases of high-grade B-cell lymphoma NOS, three of anaplastic large B-cell lymphoma, ALK-negative, 1 case of HHV8+ DLBCL NOS, and 1 of high-grade B-cell lymphoma with C-MYC and BCL2/BCL6 rearrangement. Moreover, 55 (61.1%) entities, including 37 defined by WHO 2008 and 18 defined by WHO 2016, were not represented at all. The analysis of cases registered in the ULR provides a comprehensive breakdown of the subtypes, stage distribution, and treatment of malignant lymphomas (ML) in Ukraine, supporting the usefulness of prospective data collection and timely reporting. We believe that this study is the first step toward a better understanding of the real-life outcomes of patients with ML.

A Case of Sex Cord-Stromal Tumor Originating in the Retroperitoneal Space.

A 54-year-old man was seen in the clinic with the chief complaint of epigastric pain radiating to the left groin region and a predominant postprandial abdominal discomfort. Upon examination, a painless round mass with reduced mobility was felt in the left flank during deep palpation of the abdomen. His past medical history was irrelevant. Ultrasound and IV contrast-enhanced CT scan confirmed the presence of a large tumor and an exploratory laparotomy for removal of the tumor was performed. The microscopic examination of the specimen confirmed the primary diagnosis of retroperitoneal tumor (RPT) and identified it as an extragonadal germ cell tumor with a vestigial origin, which is a rare type affecting the kidney and adrenal gland. Primitive RPTs are histologically classified as mesenchymal and neuroectodermal or vestigial. These histological types are rarely found in surgical practice and are challenging to diagnose and treat due to the peculiarities of the site of origin where they develop. RPTs are extremely rare and approximately 80% are malignant and detected lately during the disease's course, commonly discovered in advanced stages of local or systemic evolution. Currently, surgical intervention remains the only effective method of treating these tumors.

Non-Hodgkin Lymphoma Metabolism.

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid neoplasms with different biological characteristics. About 90% of all lymphomas in the United States originate from B lymphocytes, while the remaining originate from T cells [1]. The treatment of NHLs depends on the neoplastic histology and stage of the tumor, which will indicate whether radiotherapy, chemotherapy, or a combination is the best suitable treatment [2]. The American Cancer Society describes the staging of lymphoma as follows: Stage I is lymphoma in a single node or area. Stage II is when that lymphoma has spread to another node or organ tissue. Stage III is when it has spread to lymph nodes on two sides of the diaphragm. Stage IV is when cancer has significantly spread to organs outside the lymph system. Radiation therapy is the traditional therapeutic route for localized follicular and mucosa-associated lymphomas. Chemotherapy is utilized for the treatment of large-cell lymphomas and high-grade lymphomas [2]. However, the treatment of indolent lymphomas remains problematic as the patients often have metastasis, for which no standard approach exists [2].

B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

Malignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman.

Texture analysis and multiple-instance learning for the classification of malignant lymphomas.

BACKGROUND AND OBJECTIVES: Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes. METHODS: We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, and mantle cell lymphoma. RESULTS: Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin's lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients. CONCLUSIONS: The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes.

The value of cytology in diagnosis of serous effusions in malignant lymphomas: An experience of a tertiary care center.

BACKGROUND: Malignant lymphomas (ML) are often complicated by serous effusions. The present study is an attempt to cytologically assess a large series of serous effusions associated with ML, identify the immunoreactivity of cells and to evaluate the role of various ancillary methods in confirming and subtyping these cases. METHODS: A cross-sectional study of 4612 serous effusions was undertaken at the Department of Cytology, Gujarat Cancer and Research Institute by retrieving data from the year 2015 to 2017. Total 169 cases of ML, clinically suspicious, were included. All cerebrospinal fluids, serous effusions involved by myeloid neoplasms, and cases of primary effusion lymphomas were excluded from our study. Pap stained smears of all these serous effusions were examined. Ancillary methods such as immunohistochemistry were used to further subtype the positive cases using the WHO classification of hematopoietic and lymphoid neoplasms (2016). RESULTS: Out of total 169 clinically suspicious cases, 109 cases were cytologically positive for ML which included 73 (66.9%) pleural effusions, 34 (31.1%) ascitic fluids, and 2 (1.8%) pericardial effusions. T-lymphoblastic lymphoma (36.9%) and Burkitt's lymphoma (38.2%) were the most common ML involving the pleural and ascitic fluids respectively. Non-Hodgkin's lymphoma (NHL) more frequently involved the serous cavities than Hodgkin's lymphoma. (P value <.0001). Among the NHL, T-cell lymphomas more commonly lead to serous effusions than B-cell lymphomas (P value <.0048). CONCLUSION: Cytological examination of serous effusions is an accurate, prompt, affordable technique having diagnostic and therapeutic implications. With the help of ancillary methods, we can identify the phenotype of cells, classify as well as confirm our diagnosis.

Biology and therapy of primary mediastinal B-cell lymphoma: current status and future directions.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct disease closely related to classical nodular sclerosing Hodgkin lymphoma. Conventional diagnostic paradigms utilising clinical, morphological and immunophenotypical features can be challenging due to overlapping features with other B-cell lymphomas. Reliable diagnostic and prognostic biomarkers that are applicable to the conventional diagnostic laboratory are largely lacking. Nuclear factor kappa B (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT) signalling pathways are characteristically dysregulated in PMBCL and implicated in several aspects of disease pathogenesis, and the latter pathway in host immune evasion. The tumour microenvironment is manipulated by PMBCL tumours to avoid T-cell mediated destruction via strategies that include loss of tumour cell antigenicity, T-cell exhaustion and activation of suppressive T-regulatory cells. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and DA-EPOCH-R (dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) are the most common first-line immunochemotherapy regimens. End of treatment positron emission tomography scans are the recommended imaging modality and are being evaluated to stratify patients for radiotherapy. Relapsed/refractory disease has a relatively poor outcome despite salvage immunochemotherapy and subsequent autologous stem cell transplantation. Novel therapies are therefore being developed for treatment-resistant disease, targeting aberrant cellular signalling and immune evasion.

[Advanced lymphomatous tumor of the trunk]. / Tumeur évoluée du tronc d'origine lymphomateuse.

Malignant lymphomas are a group of cancers that arise in the lymphoid tissue, in the lymph nodes or in extranodal sites due to neoplastic lymphocytic cell transformation. Within this group, malignant non-Hodgkin lymphomas are distinctive. We report a case of diffuse advanced and extremely aggressive malignant cutaneous non-Hodgkin lymphoma. The study involved a 30-year old patient, driver, married and father of one child, followed-up in the Department of Hematology and Oncology for 2 years due to malignant non-Hodgkin lymphoma diagnosed on the basis of axillary and inguinal polyadenopathies. The patient underwent 13 chemotherapy sessions. He was admitted to the Department of Plastic, Cosmetic and Burn Surgery at the University Hospital Mohammed VI in Marrakech with skin involvement of his lymphoma manifesting as an advanced left latero-thoracic tumor rapidly increasing in size. On clinical examination, his general condition was quite good. It showed voluminous left latero-thoracic mass adherent to its deeper structure with ipsilateral axillary shield. Partial biopsy was performed. Anatomo-pathological examination confirmed the diagnosis of diffuse malignant large B-cells non-Hodgkin's lymphoma. Immunohistochemical and genetic study was not performed. Serology tests were negative. Serial Computed Tomography (CT) scan showed voluminous left antero-lateral predominantly axillary and thoracic ganglionic mass made of confluent lymph nodes, with persistence of peripheral lymph nodes, skin ulcers and necrotic areas measuring 30cm in diameter. In our Hospital, the patient underwent wide tumor resection, then coverage with a split-thickness skin, thus reducing tumor volume and ensuring better patient's comfort. When the patient started healing, he was referred to the Department of Hematology and Oncology for complementary treatment.

Non-Hodgkin Lymphoma Metabolism.

KEY POINTS: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid neoplasms with differing biological characteristics. About 90% of all lymphomas in the United States originate from B lymphocytes, while the remaining originate from T cells [1]. The treatment of NHLs depends on neoplastic histology and the stage of the tumor, which will indicate whether radiotherapy, chemotherapy, or a combination is the best suitable treatment [2]. The American Cancer Society describes the staging of lymphoma as follows: Stage I is lymphoma in a single node or area. Stage II is when that lymphoma has spread to another node or organ tissue. Stage III is when it has spread to lymph nodes in two sides of the diaphragm. Stage IV is when the cancer has significantly spread to organs outside the lymph system. Radiation therapy is the traditional therapeutic route for localized follicular and mucosa-associated lymphomas. Chemotherapy is utilized for the treatment of large cell lymphomas and high-grade lymphomas [2]. However, treatment of indolent lymphomas remains problematic as the patients often have metastasis for which no standard approach exists [2].

Outcome of primary cutaneous anaplastic large cell lymphoma: a 20-year British Columbia Cancer Agency experience.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30+ lymphoproliferative disorder with excellent outcomes reported despite frequent cutaneous relapses. Limited information exists on the development of systemic lymphoma. The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify all adults diagnosed with PCALCL from 1993 to 2013. From 2005, the BCCA endorsed radiotherapy (RT) alone for limited stage with data failing to support chemotherapy. Forty-seven patients were identified with a male predominance (n = 31, 66%), median age of 64 years and predominantly limited stage (n = 40, 85%). Median follow-up was 8·4 years. The 5-year time to progression (TTP) was 58% (64% limited versus 29% advanced stage). The 5-year disease-specific survival (DSS) and overall survival was 86% and 75%, respectively. In an as-treated analysis, the 5-year DSS for limited stage patients was similar comparing RT to combined modality treatment or chemotherapy alone but the 5-year TTP favoured RT (82% vs. 33%, P = 0·004). The 5-year cumulative risk of developing systemic lymphoma was 14%. Our results confirm the favourable prognosis of PCALCL despite a high relapse rate. Limited stage patients treated with RT alone have excellent outcomes. There is a small risk of systemic lymphoma in PCALCL.

A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for transplant-eligible patients with mantle cell lymphoma.

Chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma (MCL). The achievement of complete remission (CR) and minimal residual disease (MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine (RB/RC). This phase 2 study (NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD-evaluable patients who completed treatment, 93% achieved MRD negativity after RB/RC. In conclusion, RB/RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population.