A Case Report on a Rare Type of Lymphoma: Angioimmunoblastic T-cell Lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of non-Hodgkin lymphoma (NHL). We present a case of a 60-year-old female who attended the emergency department (ED) with fatigue, recurrent fever, weight loss, and adenopathy for six months. Laboratory findings showed anemia, lymphocytosis, eosinophilia, thrombocytosis, cholestasis, hypoproteinemia, and hypoalbuminemia. Abdominopelvic computed tomography (CT) revealed multiple adenopathies. A lymph node biopsy yielded inconclusive results in the outpatient clinic. Later, during admission, the patient underwent a positron emission tomography-computed tomography (PET-CT), revealing a cervical adenopathy cluster that was excised en bloc. Histology confirmed the diagnosis of AITL. The medical team initiated chemotherapy but opted for exclusive symptomatic treatment due to disease progression. The patient died six months after diagnosis. The fluctuating and nonspecific presentation of AITL can hinder and delay definitive diagnosis, therefore impacting treatment and prognosis.

FDG-PET/CT Imaging in Chimeric Antigen Receptor-Engineered T-Cell Treatment in Patients with B-Cell Lymphoma: Current Evidence.

The Food and Drug Administration and the European Medicines Agency have recently approved chimeric antigen receptor-engineered (CAR) T cells to treat several refractory/relapsed B-cell lymphomas. This comprehensive review aims to demonstrate the pivotal role that [18F]-FDG PET/computed tomographic (CT) imaging can play to enhance the care of patients treated with CAR T-cell therapy. To this end, this review deciphers evidence showing the diagnostic, prognostic, predictive, and theragnostic value of [18F]-FDG PET/CT-derived parameters.

Effective geriatric management strategies for fatal non-Hodgkin lymphoma: Insights from a case report. / Estrategias geriátricas efectivas para el tratamiento del linfoma no Hodgkin mortal: conclusiones de un estudio de caso.

This case report delves into the intricate medical history of an 85-year-old male who experienced a myriad of health challenges throughout his years. With a medical history full of conditions, such as stroke, sinus bradycardia, chronic obstructive pulmonary disease, severe pulmonary hypertension, and chronic gastritis, the patient´s health profile is further complicated by prostatic hypertrophy, persistent dorsalgia and lumbalgia, the presence of a thyroid nodule, and a recent onset of hypothyroidism. Among the diverse medical conditions of this patient, our narrative is primarily centered on his latest diagnosis: non-Hodgkin´s lymphoma. Non-Hodgkin´s lymphoma is not just a mere addition to his already complex medical history; it is a malignant neoplasm that shapes worldwide patterns of cancer mortality. The first indicators that led to this discovery were the patient´s complaints of persistent pain in the left lateral neck region associated with dysphagia. This was not an isolated symptom; the patient also reported a month-long history of asthenia, myalgias, weakness around the pelvic girdle, fatigue, and hyporexia, depicting a concerning clinical picture. Advanced diagnostic tools, namely ultrasound and computed tomography, shed light on submaxillary and cervical adenopathies. To corroborate such findings and get a definitive diagnosis of malignancy, a fine-needle aspiration was advised. Through this case, we aim not only to describe a clinical scenario but to highlight the challenges involved in the diagnosing and treatment of non-Hodgkin ´s lymphoma, especially in elderly patients. The overlap of multiple comorbidities adds further complexity to the scene, demanding meticulous care and expertise. This report serves as an educational tool for oncology experts, as well as testimony to the complexities of patient care in the oncology diagnostic and treatment setting.

Este reporte de caso se centra en el intricado historial médico de un varon de 85 años que experimenta una miriada de problemas de salud a lo largo de sus años. Con un historial médico lleno de afecciones, como accidente cerebrovascular, bradicardia sinusal, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar grave y gastritis crónica, el perfil de salud del paciente se complica aún más por la presencia de hipertrofia prostática, dorsalgia y lumbalgia persistentes, la presencia de un nódulo tiroideo y el reciente diagnóstico de hipotiroidismo. Entre las diversas afecciones de este paciente, nuestra narración se centra principalmente en su último diagnóstico: linfoma no Hodgkin. El linfoma no hodgkiniano no es un mero añadido a su ya complejo historial médico; es una neoplasia maligna que configura las tendencias de mortalidad por cáncer a nivel mundial. Los primeros indicadores que llevaron a este descubrimiento fueron las quejas del paciente por dolor persistente en la región lateral izquierda del cuello, asociado a disfagia. No se trataba de un síntoma aislado, ya que el paciente también refería desde hacía un mes astenia, mialgias, debilidad alrededor de la cintura pélvica, fatiga e hiporexia, lo que describía un cuadro clínico preocupante. Las herramientas diagnósticas avanzadas, a saber, la ecografía y la tomografía computarizada, arrojaron luz sobre las adenopatías submaxilares y cervicales. revelaron sobre las adenopatías submaxilares y cervicales.

Prognostic Significance of Bcl-2 Expression in Non-germinal Center B-cell-Like Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphomas (DLBCLs) are a group of malignant neoplasms with extensive clinical and molecular heterogeneity. Several key genetic aberrations have been identified, such as those involving the MYC, BCL6, and BCL2 genes. Prior studies on the prognostic significance of Bcl-2 protein expression in DLBCL have been contradictory, with some suggesting it has an adverse effect, while others have shown no such association. Bcl-2 is known to be more highly expressed in the non-germinal center B-cell-like (non-GCB) subtype compared to germinal center B-cell-like (GCB) DLBCL. Non-GCB status is associated with a less favorable prognosis. This study aimed to investigate whether the expression of Bcl-2 protein in non-GCB DLBCL influences response to treatment, progression-free survival, or overall survival. METHODS: In this retrospective study, we investigated whether there was a difference in the clinical outcomes of non-GCB DLBCL cases (n = 97) that were confirmed by immunochemistry to demonstrate high levels of Bcl-2 protein expression (>50% neoplastic cells stained) when compared to those who were deemed negative based on this criterion. Response to rituximab-based induction immunochemotherapy, five-year progression-free survival, and five-year overall survival were assessed. RESULTS: There was no statistically significant difference in response to treatment, five-year progression-free survival, or five-year overall survival between the patients who were positive for Bcl-2 (n = 70) compared to those who were considered Bcl-2 negative (n = 27). CONCLUSION: High levels of Bcl-2 protein expression do not appear to be of prognostic significance in non-GCB DLBCL and therefore Bcl-2 may not be a key therapeutic target in the treatment and improvement of clinical outcome in such cases.

Pattern of Clinical Presentation in Patients With Lymphoma.

Introduction Lymphomas take place when cells of the lymphatic system divide and re-divide in an uncontrolled fashion, and lymphomas have been termed as a "diverse group" of cancer, playing a major role in the area of oncology. The clinical behavior and manifestations of lymphomas in the head and neck region usually lack specific characteristics that would enable attribution to a specific lymphoma entity without biopsy and histological evidence. This study aimed to determine the frequency of common clinical features among patients with lymphoma. Methods This descriptive cross-sectional study was conducted at the Department of General Medicine, Lady Reading Hospital, Peshawar, from October 28, 2021 to April 28, 2022. The inclusion criteria consisted of individuals who were recently diagnosed with lymphoma and were between the ages of 10 and 50, regardless of their gender. This study enrolled a total of 186 patients diagnosed with lymphoma and assessed for common signs and symptoms. The data-gathering process included in-depth interviews, evaluations of medical history, physical exams, and initial investigations. The data analysis was done using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). Results The mean age of the patients was 34.5±9.6 years. Out of the total, 115 (61.8%) were men and 71 (38.2%) were women. With regard to symptoms, 134 (72%) had a fever, 80 (43%) had abdominal pain, 102 (54.8%) had vomiting, 49 (26.3%) had a headache, 111 (59.7%) had weight loss, and 17 (9.1%) had a cough. With regard to signs, 33 (17.7%) had painless lymphadenopathy, 58 (31.2%) had jaundice, 157 (84.4%) had anemia, 147 (79%) had hepatomegaly, 160 (86%) had splenomegaly, 24 (12.9%) had ascites, and 16 (8.6%) had abdominal tenderness. Conclusion The varied clinical appearance of lymphoma makes treatment difficult. In severe cases of lymphoma, early and timely diagnosis is crucial for proper and prompt treatment. The signs and symptoms, along with demographic information of patients, thorough medical history, imaging testing, and clinical examination, may indicate lymphoma.

Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report.

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Diffuse large B-cell lymphoma in the uterus with unexpected manifestations: a case report.

BACKGROUND: Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract. CASE PRESENTATION: A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor). CONCLUSION: Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.

The inhibitory and transcriptional effects of the epigenetic repurposed drugs hydralazine and valproate in lymphoma cells.

Lymphoma is a disease that affects countless lives each year. In order to combat this disease, researchers have been exploring the potential of DNMTi and HDACi drugs. These drugs target the cellular processes that contribute to lymphomagenesis and treatment resistance. Our research evaluated the effectiveness of a combination of two such drugs, hydralazine (DNMTi) and valproate (HDACi), in B-cell and T-cell lymphoma cell lines. Here we show that the combination of hydralazine and valproate decreased the viability of cells over time, leading to the arrest of cell-cycle and apoptosis in both B and T-cells. This combination of drugs proved to be synergistic, with each drug showing significant growth inhibition individually. Microarray analyses of HuT 78 and Raji cells showed that the combination of hydralazine and valproate resulted in the up-regulation of 562 and 850 genes, respectively, while down-regulating 152 and 650 genes. Several proapoptotic and cell cycle-related genes were found to be up-regulated. Notably, three and five of the ten most up-regulated genes in HuT 78 and Raji cells, respectively, were related to immune function. In summary, our study suggests that the combination of hydralazine and valproate is an effective treatment option for both B- and T-lymphomas. These findings are highly encouraging, and we urge further clinical evaluation to validate our research and potentially improve lymphoma treatment.

Real-world outcomes with novel therapies in relapsed/refractory diffuse large B-cell lymphoma.

This study used COTA de-identified data (2010-2021) of patients in the US to explore outcomes of novel therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in real-world settings. Demographics, clinical characteristics, and clinical outcomes of patients with R/R DLBCL who received novel treatments including chimeric antigen receptor T-cell (CAR T) therapy and tafasitamab- or polatuzumab-based therapies were evaluated. Overall, 175 patients with R/R DLBCL were analyzed; 73, 69, and 27 received CAR T therapy, polatuzumab-based regimens, and tafasitamab-based regimens, respectively. In patients who had ≥1 prior lines of therapy (i.e. starting second-line or later therapy; 2 L+), CAR T, polatuzumab-based regimens, and tafasitamab-based regimens achieved a median overall survival of 26.5, 7.8, and 6.3 months, respectively. Outcomes were particularly poor for patients with relapse following CAR T, indicating that polatuzumab- and tafasitamab-based regimens in 2 L + R/R DLBCL have suboptimal outcomes in the real world. Additional treatment options are needed.

Insight into Mantle Cell Lymphoma Pathobiology, Diagnosis, and Treatment Using Network-Based and Drug-Repurposing Approaches.

Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the "butterfly effect" emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact.

Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.

Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.

Non-Hodgkin lymphoma presenting with spinal cord compression: A population-based analysis of the NHL-BFM study group.

BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. CONCLUSION: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.

Mitigating infection risks: The promise and challenge of bispecific antibodies in haematological malignancies.

Bispecific antibodies have shown significant clinical efficacy in patients with relapsed/refractory B-cell non-Hodgkin lymphomas and multiple myeloma, expanding treatment options for these patients. While these advancements are promising, it is important to be aware of associated side effects, such as cytokine release syndrome, neutropenia and infections. Gonugunta et al. provide valuable insights into the infection risks linked to the use of bispecific antibodies in haematological malignancies, drawing on both clinical trial data and real-world experiences. Commentary on: Gonugunta et al. Risk of infections with bispecific antibodies in B-cell non-Hodgkin lymphomas and multiple myeloma-The current state. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19633.

Extranodal marginal zone lymphoma of the larynx: A case report and scoping review.

BACKGROUND: This scoping review aims to review cases of extranodal marginal zone lymphoma (MZL) of the larynx to establish best management practices for this rare clinical entity. METHODS: In this paper, we report a case of laryngeal MZL, in accordance with CARE guidelines. We then performed a scoping review according to PRISMA-ScR criteria of published cases of MZL involving the larynx. The following data were collected for each case: age, sex, size, location(s) involved, stage, treatment, follow-up, and recurrence duration. RESULTS: Sixty-six patients with laryngeal MZL, first reported in 1990, were identified. Characterized by its low-grade histological appearance and indolent course, laryngeal MZL is generally confined to the larynx and has an excellent prognosis with radiation used as first-line therapy. CONCLUSIONS: It is imperative for clinicians to consider lymphoma in the differential diagnosis of a laryngeal tumor from any subsite, as certain pathologies may carry high risks of metastasis.

Utility of leukocyte-associated immunoglobulin-like receptor-1 (CD305) in flow cytometric detection of minimal bone marrow involvement by B-cell non-Hodgkin lymphoma.

Multicolor flow cytometry (MFC) is crucial in detecting occult or minimal bone marrow (BM) involvement by non-Hodgkin lymphomas (NHL), which may not be detected using trephine biopsy or imaging studies. Detection of low-level BM involvement can be challenging without definite immunophenotypic aberrancies. We studied the utility of CD305 in MFC detection of minimal BM involvement by B-NHL, especially in the absence of aberrancies by commonly used markers. The study included 1084 consecutive BM samples submitted for the staging of B-NHLs (excluding CLL) over two years. Samples were studied for morphological, immunophenotypic, and histopathological assessment. MFC studies were performed using 10-13 color MFC, including CD305-antibody (clone, DX26). Minimal BM involvement was defined with a cutoff of ≤10% lymphoma cells in viable cells on MFC assessment. Of 1084, 148 samples revealed overt morphological involvement by B-NHL and were excluded from analysis. BM samples of 172/936 patients were morphologically negative but revealed involvement using MFC independently. Corresponding trephine biopsy involvement was detected in only 79/172 (45.9%) patients. On MFC, 23/172 samples showed BM involvement with >10% lymphoma cells, and 149/172 (86.6%) samples revealed minimal involvement. In 54/149 (36.24%) samples, lymphoma cells were detected only with aberrant loss of CD305 expression. In 78 of the remaining 95 samples (82.1%), it provided an immunophenotypic aberrancy addition to other markers and supported the results. CD305 is a highly useful marker in the flow cytometric assessment of minimal BM involvement by B-NHL. MFC is a superior modality to trephine biopsy in detecting low-level BM involvement.

Current landscape of CD3 bispecific antibodies in hematologic malignancies.

Over the past 30 years the incorporation of monoclonal antibody (mAb) treatments into the management of hematologic malignancies has led to significant improvements in patient outcomes. The key limitation of mAb treatments is the necessity for target antigen presentation on major histocompatibility complex (MHC) and costimulatory molecules to elicit a cytotoxic immune response. With the advent of bispecific antibodies (BsAbs), these limitations can be overcome through direct stimulation of cytotoxic T cells, thus limiting tumor cell evasion. BsAbs are rapidly being incorporated into treatment regimens for hematologic malignancies, and there are now seven FDA-approved treatments in this class, six of which have been approved in the past year. In this review we describe the function, complications, and clinical trial data available for CD3 BsAbs in the treatment of lymphoma, myeloma, and leukemia.

Harnessing natural killer cells for refractory/relapsed non-Hodgkin lymphoma: biological roles, clinical trials, and future prospective.

Non-Hodgkin lymphomas (NHLs) are heterogeneous and are among the most common hematological malignancies worldwide. Despite the advances in the treatment of patients with NHLs, relapse or resistance to treatment is anticipated in several patients. Therefore, novel therapeutic approaches are needed. Recently, natural killer (NK) cell-based immunotherapy alone or in combination with monoclonal antibodies, chimeric antigen receptors, or bispecific killer engagers have been applied in many investigations for NHL treatment. The functional defects of NK cells and the ability of cancerous cells to escape NK cell-mediated cytotoxicity within the tumor microenvironment of NHLs, as well as the beneficial results from previous studies in the context of NK cell-based immunotherapy in NHLs, direct our attention to this therapeutic strategy. This review aims to summarize clinical studies focusing on the applications of NK cells in the immunotherapy of patients with NHL.

The development of a prediction model based on random survival forest for the prognosis of non- Hodgkin lymphoma: A prospective cohort study in China.

Background and objective: The pathological staging of non-Hodgkin lymphoma (NHL) is complex, the clinical manifestations are varied, and the prognosis differ considerably. To provide a useful reference for early detection and effective treatment of NHL, we developed a random survival forest (RSF) prognostic model based on machine learning (ML) algorithms using prospective cohort data collected from Chongqing Cancer Hospital from Jan 1, 2017 to Dec 31, 2019 (n = 1449) to compare with the traditional cornerstone method Cox proportional hazards (CPH) model and evaluate the predictability of the model. Methods: Patients were randomly split into a training cohort (TC) and validation cohort (VC) based on 65/35 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extracted the important features. And the RSF was modeled to explore the prognostic factors impacting the overall survival (OS) of patients with NHLs in the TC and validated in the VC. The C-index, the Integrated Brier Score (IBS), Kaplan-Meir method, the receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) were selected to measure performances and discriminations of the models. In addition, individual survival probability predicted for NHL patients. Results: According to the features extracted by LASSO model and univariable Cox model, 16 variables were selected to develop the RSF model with log-rank splitting rule, which were age, ethnicity, medical insurance, Ann Arbor stage, pathology, targeted-therapy, chemo-therapy, peripheral blood neutrophil count to lymphocyte count ratio (NLR), peripheral blood platelet count to lymphocyte count ratio (PLR), serum lactate dehydrogenase (LDH), CD4/CD8, platelet (PLT), absolute neutrophil count (ANC), lymphocyte (LYM), B-symptoms, and (CPR) were important prognostic factors. Compared to the CPH model (C-index = 0.748, IBS = 0.166), the RSF model (C-index = 0.786, IBS = 0.165) is outperformed in predictability and accuracy. The AUC of the RSF model to estimate the 1-, 3-, and 5-year OS in TC were 0.847, 0.847, and 0.809, respectively; while those in the CPH were 0.816, 0.803, and 0.750, respectively. Conclusions: To provide practical implications for the implementation of individualized therapy, the study constructed a high-performed RSF model and reveal that it outperformed the traditional model CPH. And the RSF model ranked the risk variables. In addition, we stratified the risk of NHL patients and estimated individual survival probability based on the RSF model.

Contrast-enhanced ultrasound findings of primary hepatic non-Hodgkin's lymphoma: a case report.

Primary hepatic lymphoma (PHL) is rare, and its early diagnosis is difficult. This article presents a primary hepatic non-Hodgkin's lymphoma (NHL) case report. A 52-year-old woman was admitted to the hospital due to a fever. After undergoing laboratory examination, contrast-enhanced computed tomography (CT), ultrasound, and contrast-enhanced ultrasound (CEUS), only CEUS suggested malignancy. Then, the patient underwent a laparoscopic liver biopsy, which diagnosed NHL. Previous studies have shown that hepatic lymphoma is a hypoglycemic tumor, and the enhanced CT and magnetic resonance imaging (MRI) scans are mostly mildly intensified. At the same time, the two-dimensional and color Doppler ultrasonography are mostly atypical. CEUS has unique advantages in displaying micro-vessels, which can be helpful in the diagnosis of primary hepatic lymphoma.