Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s lymphoma.Whether patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully investigated.therapy have cognitive impairment has not been fully investigated.AIM To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.METHODS The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after chemo-therapy.RESULTS The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT groups.CONCLUSION Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

SENEX-mediated CDK4/6 inhibition promotes senescence and confers apoptosis resistance in B-cell non-Hodgkin lymphoma

Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic significance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining specific inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the specific cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.

Primary Non-Hodgkin’s Malignant Lymphoma of the Uterus at the Reference Hospital of Maradi/Niger: A Case Report

Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass in a 50-year-old patient with no previous history of the disease. It was classified as Ann Arbor IV Bb after imaging, given the medullary infiltration and signs of clinical and biological evolutivity: the patient had received two courses of chemotherapy, CHOP protocol. She died 23 days after the second treatment due to a hypertensive crisis.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

Heterochronous multiple primary prostate cancer and lymphoma:A case report

BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma(DLBCL).CASE SUMMARY We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide(50 mg per day)and an extended-release implant of goserelin(1/28 d).Seven years later,rectal DLBCL with lung metastases was found.CONCLUSION Although rare,the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.

Massive bleeding in small intestinal mucosa-associated lymphoid tissue lymphoma associated with COVID-19 infection:a case report

The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated with the gastrointestinal tract,and the involvement of small intestinal is rare.Recent studies have established a close relationship between novel coronavirus 2019(COVID-19)and the occurrence and progression of various diseases.This article presents a rare case of a small intestinal MALT lymphoma.The patient was initially admitted with COVID-19 pneumonia and subsequently developed gastrointestinal bleeding during hospitalization.Medical and endoscopic treatments were ineffective,and an emergency exploratory laparotomy was performed.The affected segment of the small intestine was excised,and a pathological biopsy confirmed the diagnosis of MALT lymphoma.This case underscores the significance of raising clinical awareness of this condition among health care professionals.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Primary early-stage intestinal and colonic non-Hodgkin's lymphoma: Clinical features, management, and outcome of 37 patients

AIM： To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin＇s lymphoma （PICL）. METHODS： A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS： Twenty-five patients presented with Ann Arbor stage Ⅰ PICL and 12 with Ann Arbor stage Ⅱ PICL. Thirty-five patients underwent surgery （including 31 with complete resection）, 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival （OS） rates were 51.9% and 44.5%. The corresponding diseasefree survival （DIS） rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment （P= 0.001）. While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS （P = 0.031） for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemotherapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy.CONCLUSION： Combined surgery and chemotherapy is recommended for treatment of patients with PICL, Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.

A case of primary isolated non-Hodgkin’s lymphoma of the esophagus in an immunocompetent patient

Primary non-Hodgkin’s lymphoma of the esophagus is a rare disease.A case of primary isolated nonHodgkin’s lymphoma of the esophagus in a 77-yearold man without acquired immunodeficiency syndrome is presented.We describe the clinical features and the imaging findings(barium swallow,endoscopic ultrasonography and CT)of a biopsy proven B-cell lymphoma with diffuse transmural involvement of the esophagus wall,which was discovered incidentally.We also briefly review the literature.

Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients

AIM： To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin＇s gastric lymphoma. METHODS： We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS： HLA-DR antigen expression was detected in 33 gastric lymphoma patients （91.7%） and 6 nonmalignant patients （54.5%）. PECAM-1 stained tumor cells of 10 patients （27.8%）, endothelial cells of 9 patients （25%） and inflammatory infiltrate of 4 patients （40%） with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients （47.2%）, while 5 non-malignant patients （50%） were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively （P= 0.009 and P= 0.003）. In the univariate analysis, PECAM-1（＋）/ICAM-3（-） and HLA-DR（-）/ICAM-3（-） patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns （P=0.0041 and P= 0.0091, respectively）. Those patients who were HLA-DR（＋ ）/ICAM-3（＋ ）/PECAM-I（-） （n = 8） had a significantly higher survival rate compared to the rest of the group （n = 24） （P= 0.0289）. CONCLUSION： PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

The expression of cyclooxygenase-2 （COX-2） and p16 in non-Hodgkin＇s lymphomas and its clinical significance

Objective： To investigate the expression of cyclooxygenase-2 （COX-2） and p16 proteins in non-Hodgkin＇s lymphomas （NHL） and their relationship with the genesis and progress of it. Methods： The expression of COX-2 and p16 protein were studied in the lymph nodes tissue from 60 NHL patients and 10 control patients with non-malignant diseases by flow cytometry. Results： Positive rate of COX-2 protein expression in NHL tissues （63.3%, 38/60） was higher than that in normal lymphaden tissues （0, 0/10）. The difference was significant between the two groups （P 〈 0.01）. Expression of COX-2 protein was related with the clinical stage of NHL. In stage Ⅰ ＋ Ⅱ patients, it was significantly lower （35.0% ± 54.6%） than that in stage Ⅲ ＋ Ⅳ patients （84.6% ±87.5%） （P 〈 0.01）. In different sex, age, tumor malignant degree, IPI grade, extranodal involvement and B symptoms groups, the differences of COX-2 expression were not statistically significant （P 〉 0.05）. Positive rate of p16 protein expression （41.7%, 25/60） in NHL＇ was statistically lower than that in normal lymphomas （100%, 10/10） （P 〈 0.01）. Expression of p16 protein was related to malignant degree of NHL. The positive rates of p16 protein in low malignant degree tissues （64.7%, 11/17） was higher than that in high malignant degree tissues （14.3%, 2/14） （P 〈 0.05）. Positive rates of p16 protein of NHL tissues in different sex, age, IPI grade, extranodal involvement, clinical stages and B symptoms were not statistically significant （P 〉 0.05）. The p16 protein expression in COX-2 positive patients was 47.4% （18/38）, and in negative patients it was 31.8% （7/22）. There was no statistically difference between them （P 〉 0.05）. Correlation analysis revealed there was no correlation between expression of COX-2 and p16 protein. Conclusion： Both COX-2 and p16 protein may all have relationship with the genesis and progress of NHL. The expression of COX-2 protein in NHL may be a poor prognostic indicator. COX-2 and p16 protein probably have different mechanisms in the genesis and progress of NHL. Their relationship is firstly put forward in this article and needed further studying.

Primary intestinal non-Hodgkin's lymphoma:A clinicopathologic analysis of 81 patients

AIM:To analyze the clinicopathologic features and the prognosis of primary intestinal lymphoma.METHODS:Patients were included in the study based on standard diagnostic criteria for primary gastrointesti-nal lymphoma,and were treated at Sun Yat-sen Univer-sity Cancer Centre between 1993 and 2008.RESULTS:The study comprised 81 adults.The most common site was the ileocaecal region.Twenty-two point two percent patients had low-grade B-cell lym-phoma.Fifty-one point nine percent patients had high-grade B-cell lymphoma and 25.9% patients had T-cell lymphoma.Most patients had localized disease.There were more patients and more early stage diseases in the latter period,and the origin sites changed.The ma-jority of patients received the combined treatment,andabout 20% patients only received nonsurgical therapy.The wverall survival and event-free survival rates after 5 years were 71.6% and 60.9% respectively.The mul-tivariate analysis revealed that small intestine and ileo-caecal region localization,B-cell phenotype,and normal lactate dehydrogenase were independent prognostic factors for better patient survival.Surgery based treat-ment did not improve the survival rate.CONCLUSION:Refined stratification of the patients according to the prognostic variables may allow indi-vidualized treatment.Conservative treatment may be an optimal therapeutic modality for selected patients.

Non-Hodgkin's Lymphoma Primarily Presenting with Fanconi Syndrome and Acute Kidney Injury

KIDNEY involvement is common in non-Hodgkin＇s lymphoma （NHL） with incidence up to 30%-40% in autopsy studies. However, it us- ually occurs late in the course of the diseaseand is clinically silent. Clinically overt renal disease including acute kidney injury （AKI） as its primary manifestation is rarely reported, moreover, Fanconi syndrome （FS） is extremely rare as the main manifestation in NHL. In this report, we presented a case of NHL primarily presenting with FS and AKI due to diffuse interstitial infiltration of NHL cells and emphasized the important role of renal biopsy, especially renal immunohistochemical analysis in the diagnosis of renal diffuse lymphoma.

Primary gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate

Primary malignant lymphoma of the prostate is exceedingly rare.Here we report a case of a 65-year-old man who presented with increased urinary frequency,urinary urgency,and urinary incontinence for two years.Benign prostatic hypertrophy was suspected at primary impression.Ultrasound revealed a hypoechoic lesion of the prostate.The total serum prostate-specific antigen was within normal range.Positron emission tomography/computerized tomography(PET/CT)showed a hypermetabolic prostatic lesion.Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma.There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging.18F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging,but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Pediatric-type follicular lymphoma in a Crohn’s disease patient receiving anti-α4β7-integrin therapy:A case report

BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces inflammatory lymphocyte trafficking into the intestinal mucosa.This effect is believed to be confined to the colon.CASE SUMMARY We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma.Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens.Rituximab,cyclophosphamide,vincristine,and prednisone chemoimmunotherapy resulted in durable lymphoma remission,and vedolizumab treatment was continued.While the patient’s T-lymphocyte population and immunoglobulin production recovered,the T-lymphocyte mitogen response remained suppressed.CONCLUSION This patient’s NHL may be linked to receiving anti-α4β7 therapy.Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.

Dysentery caused by Balantidium coliin a patient with non-Hodgkin's lymphoma from Turkey

Balantidium coli is the only parasitic ciliate of man. It is a flattened oval organism covered with cilia, and a gullet at the anterior end. It is infrequently pathogenic for man,although epidemic buds in tropical zones have been described. The infection fundamentally affects the colon and causes variable clinic pictures, from asymptomatic to serious dysenteric forms. We present a case of parasitologically diagnosed as causes of diarrhea in a patient with non Hodgkin's lymphoma from Turkey.In order to find out the causative etiologic agent of diarrhea,stool samples were examined by native,lugol and flotation methods and we detected moving trophozoites, which were approximately 60μm long and 35μm wide.These bodies were diagnosed as Balantidium coli This case underlines that Balantidium coli should also be considered as a possible pathogen in immunocompromised patients with diarrhea.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

Hepatitis viruses and non-Hodgkin's lymphoma: A review

Non-Hodgkin's lymphoma(NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.