Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHLs.This report aims to explore the efficacy and safety of rituximab combined with Bruton tyrosine kinase inhibitors(BTKis)in the treatment of elderly patients with DLBCL.CASE SUMMARY The clinical data of two elderly patients with DLBCL who received rituximab combined with BTKi in our hospital were retrospectively analyzed,and the literature was reviewed.The patients were treated with chemotherapy using the R-miniCHOP regimen for two courses.Then,they received rituximab in combination with BTKi.CONCLUSION The treatment experience in these cases demonstrates the potential efficacy of rituximab combined with BTKi to treat elderly DLBCL patients,thus providing a new treatment strategy.

Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.

Case Report: Fever of Unknown Origin <br/>—An Unusual Presentation for Diffuse Large B-Cell Lymphoma

A 61-year-old male initially presented with fever of unknown origin. He had extensive work-up over two years including an infectious diseases panel, autoimmune studies, and Rheumatology and Hematology evaluations. The patient was initially diagnosed with Adult Still’s disease and underwent an out-patient right nodal fine-needle aspiration that was indeterminate. After continued failure of treatment for Adult Still’s disease, the patient had surgical resection of a right axillary lymph node that yielded the diagnosis of diffuse large B-cell lymphoma. Further work-up revealed Epstein-Barr virus positivity, the possible trigger behind his mutation for diffuse large B-cell lymphoma and its uncommon presentation. The patient met criteria for central nervous system prophylaxis and received multiple administrations throughout his therapy. He ultimately expired following recurrence of his disease at its initial site but without central nervous system involvement. We report an uncommon presentation of a patient with diffuse large B-cell lymphoma. This lymphoma can have numerous, vague presentations requiring a broad differential diagnosis and may lead to multiple evaluations prior to an ultimate diagnosis. We will also discuss the need for central nervous system prophylaxis, how this patient is qualified for prophylaxis, and how central nervous system prophylaxis benefits, harms, or does not affect patients with diffuse large B-cell lymphoma.

Individualized Treatment and Palliative Care for A90-Year-Old Patient with Primary Gastric Diffuse Large-B Cell Lymphoma:4 Year Follow-up and Inspiration

A 90-year-old man was diagnosed with primary gastric diffuse large B-cell lymphoma(PGDLBL)by PET/CT examination,gastroscopy,biopsy and histopathological analysis at a regular physical check in April,2016.The patient received R-CO chemotherapy(rituximab,cyclophosphamide,and vincristine)and radiotherapy subsequently,with enteral nutritional treatment through 3-cavity nasogastric tube due to development of pyloric obstruction.To satisfy patient's strong desire of eating by himself,we performed surgery of exploratory laparotomy and Roux-en-Y gastric bypass(RGB)to relieve pylorus obstruction.Postoperatively,the patient resumed oral feeding,supplemented by nasogastric tube feeding at 1350-1550 Kcal daily.He is now 94 years old with fairly well nutrition and normal communication.The outcome of 4 year follow-up suggests that nutritional treatment and palliative medicine are important for improving prognosis and life-quality of very elderly patients with end-stage tumors apart from the effective chemotherapy,radiotherapy,and surgery.

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.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Non-anthracycline chemotherapy associated with a poor outcome in elderly Egyptian patients with diffuse large B-cell non-Hodgkin lymphoma

Aim:Rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone(CHOP)is the standard treatment for patients with diffuse large B-cell non-Hodgkin lymphoma(DLBCNHL).Nevertheless,anthracyclines are contraindicated for some patients,e.g.cardiac dysfunction,severe hepatic dysfunction,jaundice.Thus,this study assessed the effectiveness of non-anthracycline chemotherapy regimen cyclophosphamide,vincristine,and prednisone(CVP)in elderly DLBCNHL patients vs.the standard CHOP.Methods:This retrospective study included 418 DLBCNHL patients diagnosed between 2003 and 2006 and followed until March 2014.During this period of time,rituximab was not available for all patients,particularly for patients older than 60 years.Results:CHOP and CVP were administered to 351(84%)and 67(16%)patients,respectively.Older age and comorbidities,particularly cardiovascular and diabetes mellitus,were independent determinants for not receiving CHOP.Patients received more courses of CHOP treatment than that of CVP(6 vs.3 courses;P<0.001)and developed more toxicities(48.4%vs.23.9%;P<0.001),particularly fatigue,alopecia,and gastrointestinal tract toxicities.Complete response rate was higher in CHOP than in CVP(69.9%vs.29.9%;P<0.001).Moreover,early death was significantly higher in CVP group of patients than in CHOP(43.3%vs.8.6%;P<0.001).After a median follow-up of 71 months,the median overall survival(OS)and event-free survival(EFS)were signifi cantly better in CHOP than in CVP(49.5 vs.3.7 months and 32.2 vs.3.5 months;P<0.001 for both,respectively).Older age,poor age-adjusted International Prognostic Index scores,not receiving CHOP or consolidative radiotherapy were independent predictors of poor OS and EFS.Conclusion:Use of the CVP regime to treat DLBCNHL patients who were unfit to the standard CHOP treatment was associated with lower remission rates and poorer EFS and OS in this group of patients.

A retrospective analysis of real-world outcomes of elderly Chinese patients with diffuse large B-cell lymphoma

Background:Elderly patents with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients,and the optimal treatment strategy for this group remains controversial.We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group.Methods:From April 2006 to December 2012,a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College were included in this analysis.Patients were further divided into two age groups (61-69 years and ≥70 years).We compared clinical characteristics and outcomes between groups.Results:Of 349 total patients,204 (58.5%) were aged 61 to 69 years,and 145 (41.5%) patients were aged 70 years or older.Except for the Eastern Cooperative Oncology Group performance status,clinical characteristics were comparable between the two groups.With a median follow-up of 82 (range,1-129) months,the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%,respectively.The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8%(P =0.007),respectively,and the 5-year PFS rates were 51.0% and 38.6%(P =0.034).Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs.37.1%,P < 0.001) and PFS rate (56.6% vs.31.8%,P < 0.001) than chemotherapy alone.For patients aged 61 to 69 years,chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs.46.4%,P =0.002) and PFS rate (60.0% vs.38.1%,P =0.002) than chemotherapy alone.For patients aged ≥70 years,there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate:57.7% vs.25.4%,P < 0.001;5-year PFS rate:51.3% vs.23.9%,P < 0.001) compared with that seen in those who received chemotherapy alone.Multivariate analysis established that stage Ⅲ/Ⅳ disease,elevated lactate dehydrogenase (LDH),initial treatment,and chemotherapy with rituximab were independent risk factors for 5-year OS,and stage Ⅲ/Ⅳ disease,elevated LDH,and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL.Conclusions:In comparison to patients aged 61 to 69 years,those aged ≥70 years have poorer survival.Prolonged survival is obtainable with rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups,indicating that the R-CHOP-like regimen should be considered for this population,even for those aged 70 years or older.

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.

Non Hodgkin’s Lymphoma with Right Atrial Intra Cardiac Metastases

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is the most variant of Non-Hodgkin’s Lymphoma (NHL) and also the most common variant with secondary intracardiac masses. Case summary: 7 years old child presented to emergency with acute decompensated cardiac failure, ascites and tender hepatomegaly. 2D echo evaluation was suggestive of large intracardiac mass in the right atrium almost completely obstructing Tricuspid valve orifice, gross pericardial effusion and dilated Inferior Vena Cava (IVC). Emergency tumor excision surgery was performed which revealed 4 × 4 cm pinkish firm mass arising from anterior Tricuspid annulus which was completely excised. Child was extubated on postoperative day (POD) 0 and was on minimal inotropic support. Ascites reduced significantly on POD1 allowing abdominal palpation which revealed a mass in the epigastric region. This prompted evaluation by pediatrician and oncology workup suggestive of increased 18-Flouro Deoxy Glucose (18-FDG) uptake in the mediastinum, abdomen, bilateral proximal thighs, all mediastinal lymph nodal stations, bilateral lung hilar stations 10R, 10L involving all encasing the heart and great vessels with pleural deposits, Celiac trunk, superior Mesenteric Artery (SMA), Portal vein, IVC and abdominal aorta. Histo pathology Examination (HPE) and Immuno Histo Chemistry (IHC) of intracardiac mass revealed DLBCL which is metastatic in nature. Chemotherapy was started as per (French American British Lymphomes Malins B) FAB LMB-96 protocol with the child currently in the Induction phase having poor prognosis and less survival interval. Conclusion: Surgery can be considered a treatment option for metastatic intracardiac masses during emergency scenarios like cardiogenic shock to relieve obstruction along the pathway of blood flow in the heart even though we may not be able to completely excise the tumor surgically.

CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions

Chimeric antigen receptor(CAR)T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma,mantle cell lymphoma,and follicular lymphoma,with multiple FDA-approved CAR T products now commercially available.Ongoing studies seek to move CAR T-cells to earlier lines of therapy and to characterize the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia.Other areas of active research address CAR T in combination with other lymphoma-directed therapies,and mechanisms of CAR T resistance.This review focuses on the FDA-approved anti-CD19 CAR T products for B-cell lymphomas,management of CAR T-cell-associated toxicities,approaches to bridging therapy,and ongoing clinical trials and future research directions across a broad range of lymphoma histologies.