Indolent Lymphoma Research Articles

Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases receiving cytotoxic therapy: results of LEGERITY, a multicenter retrospective-and-prospective observational post-marketing study

Aim. To evaluate the effectiveness and safety of Extimia® BIOCAD (international non-proprietary name: empegfilgrastim) to reduce the incidence and duration of neutropenia, the incidence of febrile neutropenia (FN) and infections associated with FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy.
 Materials and methods. The paper presents the results of a multicenter retrospective-and-prospective observational post-marketing study of the safety and effectiveness of Extimia® BIOCAD (international non-proprietary name: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy. Initially, the study was defined as retrospective-and-prospective. However, only 2 of 671 (0.3%) patients were included retrospectively. Thus, the study is based on the evaluation of prospectively collected data. The analysis describes the characteristics and treatment of 671 patients diagnosed with lymphoma who received one or more cycles of chemotherapy in the LEGERITY study. The endpoints of interest included the incidence of grade 3–4 neutropenia, FN, and grade 3–4 infectious complications, the frequency of antibiotic therapy, and the incidence of all adverse reactions in patients who received at least one dose of the study medication.
 Results. A total of 671 patients were enrolled in the study, the majority having B-cell non-Hodgkin lymphoma (428/671, 64%) and Hodgkin lymphoma (211/671, 31%). The mean age was 54 years (18–84); 35% (236/671) of patients were elderly (over 60). The number of injections of empegfilgrastim for the entire observation period was 3093 (n=671). Adverse events were reported in 57/3093 (1.8%) cases. The most common adverse events were mild to moderate ossalgia and myalgia (27/671, 4%), back pain, and arthralgia (12/671, 1.8%), which did not require drug therapy. Two patients developed serious adverse reactions – CTCAE v.5 grade 4 hypotension events. 529 (78.8%) patients received at least 4 courses of chemotherapy. FN was reported in 14 (2.6%) patients and did not require antimicrobial therapy.
 Conclusion. The final analysis results confirm the high clinical efficacy and safety of the Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim (Extimia®) in patients with indolent and aggressive lymphomas. The data obtained from real-world clinical practice demonstrate a favorable safety and tolerability profile of empegfilgrastim in all age groups, including the elderly population.

An Unusual Occurrence of Immunoproliferative Small Intestinal Disease in Elderly Patient Presenting with Chronic Diarrhea - A Rare Case Report

Immunoproliferative small intestinal disease (IPSID) is a rare type of indolent B-cell lymphoma. It is a variant of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue. It is commonly seen in older children and young adults in the age group of 10-35 years. It is more common in males with Male: Female ratio of 2.4:1. Duodenum and jejunum are the commonly involved areas in small intestine. Colicky abdominal pain and intermittent diarrhoea are the common symptoms. Here by, we report a rare case in a 74-year-old male patient presented with chief complaints of abdominal pain, diarrhea and weight loss for 3 months. CT scan findings revealed thickening of small intestinal wall and mesenteric lymphadenopathy. Upper gastrointestinal endoscopy findings revealed nodular and ulcerative mucosa in the duodenum. Histopathological examination revealed flattening of mucosa with villous atrophy, destruction of crypts and intraepithelial lymphocytic infiltrate is noted. Interstitium shows dense and diffuse collection of lymphoplasmacytic infiltrate. Immunohistochemistry was done and it showed CD20 positive lymphoid cells. Based on the above findings the case was reported as Immunoproliferative small intestinal disease. Clinicians should suspect IPSID in cases presenting with chronic diarrhea and abdominal pain refractory to treatment. Immunoproliferative small intestinal disease has indolent clinical course and it can be cured with antibiotics in early stages. Late stages have high mortality rate and has poor prognosis. Keywords: IPSID, Alphachain disease, B cell lymphoma, duodenum, villous atrophy, lymphoplasmacytic infiltrate

Mesenteric small cell lymphocytic lymphoma presenting as acute intestinal obstruction: A rare case scenario

Small-cell lymphocytic lymphoma is a rare type of B-cell non-Hodgkin lymphoma. It is known as one of the indolent lymphomas. Moreover, sigmoid volvulus as an initial presentation is extremely uncommon. We encountered a unique case of mesenteric small cell lymphocytic lymphoma that presented with sigmoid volvulus as the initial clinical presentation. A 55-year-old male presented with 7-day history of abdominal pain, abdominal distension for 6 days, and non-passage of stool and flatus with recurrent vomiting for 3 days. Abdominopelvic computed tomography revealed a distended small bowel with volvulus of sigmoid colon with twisting of its mesentery with inter-ileal as well as free peritoneal collections of fluid. A manual untwisting counterclockwise of the volvulus followed by resection and anastomosis at a point where the bowel has apparent normal thickness and color along with excisional biopsy of the enlarged lymph node. Histopathology confirmed the diagnosis of small-cell lymphocytic lymphoma. Mesenteric lymphomas are less likely to present with sigmoid volvulus as the initial clinical presentation due to their extraluminal location and also they are indolent in course. Early diagnosis and its management reduce morbidity and mortality.

Diagnostic capabilities of instrumental methods for studying early cardiovascular adverse events in patients with lymphoproliferative disorders, quality and safety issues

Aim. To study the possibilities of instrumental research methods in relation to the earliest detection of cardiovascular events in oncohematological patients receiving antitumor immunochemotherapy, as well as to deter­mine the requirements for documenting adverse events.Material and methods. For the study, 63 patients were prospectively selected with a diagnosis of indolent non-Hodgkin lymphoma, who were indicated for antitumor immunochemotherapy. The patients were examined in three stages (before treatment, after 3 and 6 cycles of therapy) and divided into 2 groups by simple randomization. Cardiovascular toxicity in the main group of patients was assessed using 3D transthoracic echocardiography, analysis of left ventricular (LV) global longitudinal systolic strain and electrocardiography. The control group underwent a standard 3D echocardiography with analysis of LV ejection fraction. Clinical manifestations of cardiovascular events were assessed in all patients during treatment.Results. According to the study, significant changes were obtained in LV ejection fraction on the third visit — a decrease from 58,9±1,07 to 48,1±0,73% (p<0,05) and from 57,7±1,13 to 49,4±0,58% (p<0,05) in patients of the main and control groups and global longitudinal LV strain from |21,1±1,18 to |14,0±1,61 |% (p<0,05) in patients of the main group. A mixed clinical phenotype of cardiovascular toxicity was the most common among all patients. An integrated approach to the early diagnosis of cardiovascular events makes it possible to identify a larger percentage of patients with subclinical myocardial dysfunction.Conclusion. The long period of latent cardiovascular toxicity emphasizes the need for early verification of cardiovascular complications of antitumor therapy and expansion of the established paraclinical diagnostic minimum. In addition, taking into account the accumulated experience, recommendations are presented for the preparation of medical documentation in order to ensure the safety and quality of care.

Venetoclax plus dose-adjusted R-EPOCH (VR-DA-EPOCH) or G-EPOCH bridging to subsequent cellular therapy for the patients with transformed lymphoma a single center clinical experience

Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4–29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.

Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors.

Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with anti-tumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/ refractory mature B-cell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase II dose (RP2D) (clinicaltrials gov. Identifier: NCT02857998). Overall, 134 Chinese patients were enrolled (dose escalation, N=27; dose expansion, N=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d.), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d.. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% confidence interval: 37.5- 64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the dose-expansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased dose-proportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed anti-tumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.

Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia.

Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation-such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) -had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, 50.4 vs 23.5 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.

Health-Related Complications during Follow-Up and Their Impact on Blood Cancer Survivors: Results from the “Aftercare in Blood Cancer Survivors” (ABC) Study

Introduction: Blood cancer survivors are at increased risk for medical complications. Methods: Our questionnaire-based study involved 1,551 blood cancer survivors with a ≥3-year interval since the last intense treatment. Its goal was to quantify health-related complications during follow-up and assess their impact on the patients’ lives. Results: A total of 20.4% of the responding survivors reported a disease relapse, most often in indolent lymphomas. Second primary malignancies occurred in 14.1%, primarily in lymphoma and allogeneic transplantation survivors. The most frequent malignancy was basal cell carcinoma of the skin, but myeloid malignancies, melanoma, bladder, head-and-neck, and thyroid cancer also appeared disproportionately frequent. An increased infection rate was reported by 43.7%, most often after allogeneic transplantation. New cardiovascular diseases were reported by 30.2%, with a high rate of thromboembolic events in multiple myeloma (MM) and myeloproliferative diseases. Polyneuropathies were reported by 39.1%, most often by survivors with a history of MM or aggressive lymphoma. Disease relapse was perceived as the highest burden, followed by second primary malignancy, increased infection frequency, and polyneuropathy. In each area investigated, the range of perceived severities was wide. Conclusions: Health-related complications are frequent during blood cancer follow-up, with significant repercussions on the patients’ lives.

Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.

The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes.

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population-based SEER data (2015-2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population-based SEER rates for indolent B-cell (follicular and marginal zone) and T-cell lymphomas, but were 10%-15% higher than SEER rates for aggressive B-cell subtypes (diffuse large B-cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.

P-20 Primary hyperparathyroidism associated with maltoma of the thyroid gland: imaging challenges

Abstract Introduction Primary hyperparathyroidism (PHP) and malignancies are the most common causes of hypercalcemia. Nevertheless, PHP might be observed in coexisting with malignancies. We aimed to present a patient who underwent surgery for PHP and was diagnosed with thyroid MALToma. Clinical Case A 65-year-old female presented with fatigue for one year. The patient's medical history was unremarkable. On examination, thyroid gland was non-palpable. On laboratory, serum calcium (Ca), phosphorus (P) and parathormone (PTH) levels were 11 mg/dL (R: 8.8-10.6), 2.4 mg/dL (R: 2.5-4.5) and 157 pg/mL, respectively; vitamin-D was 23.63 µg/L and increased urinary Ca (400 mg per-day). She was euthyroid, and thyroid antibody elevated. Ultrasound (US) revealed multiple hypoechoic areas and a lesion (18×14 mm) in the vicinity of inferior right thyroid gland. Parathyroid scintigraphy revealed significant increase of metabolic activity posterior to the right lobe of the thyroid. She underwent right thyroid lobectomy thyroidectomy. Pathology revealed mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid. No parathyroid lesion noted. Then she was referred to our clinic. US revealed hypoechoic areas at remaining thyroid with no extra finding. We performed tru-cut biopsy from thyroid lesion. On immunochemistry, lymphoid cells were diffusely immunoreactive for CD3, CD5, CD20 and CD43 in the ymphocytes. Ki-67 index was 40%. Hence, the diagnosis of MALT lymphoma of the thyroid gland in the background of Hashimoto's thyroiditis. PTH staining of patient's previous pathology specimen was unremarkable. Pretreatment baseline 18F-flurodeoxyglucose PET/CT (FDG) revealed increased uptake (SUVmax: 5.1) in hypodense nodular structure in the posterior left lobe of the thyroid gland (Figure 1). FDG was suggestive of stage IE. Mild 18F-FCH uptake was observed suspected as parathyroid lesion next to the inferior left lobe. 4D-CT showed similar results. All imaging methods and we examined patient via US that revealed hypoechoic lesion with polar blood supply in the left lobe inferior (parathyroid adenoma). The patient were under rituximab 375 mg/m2 per week for 4 cycles. At the end of treatment, there were no sign of residual disease. Reoperation has not been planned due to the improvement of the patient's symptoms, and lymphoma with indolent course. Conclusion 10% of PHP cases may have a concomitant malignancy, while association with lymphoma is even rarer. MALT lymphoma of the thyroid gland is a rare malignancy with an indolent course. The combination of these two rare conditions hard to orchestrate. As in our case, detection of parathyroid lesions becomes more difficult in the background of a low grade lymphoma. Indolent lymphomas have limited sensitivity with FDG. FCH could be more sensitive for discriminating parathyroid lesions and indolent lymphomas. It may be useful to confirm the localization of the PHP in such cases using multiple techniques involving FCH.Figure 1.Pre-treatment avid FCH uptake (A, B) and mild FDG uptake (C, D) related with thyroid MALToma; post-treatment complete remission shown in FDG (E, F); highly vascular paratracheal lesion at 4D-CT (G, H asterixis), the same lesion with mild FCH uptake (I-N arrows) and the same lesion with hypoechoic sonographic appearance evaluated as parathyroid adenoma (O arrow).

Bispecific antibodies in indolent B-cell lymphomas.

The advent of immunotherapy in lymphomas, beginning with Rituximab, have led to paradigm shifting treatments that are increasingly bringing a greater number of affected patients within the ambit of durable disease control and cure. Bispecific antibodies harness the properties of the immunoglobulin antibody structure to design molecules which, apart from engaging with the target tumour associated antigen, engage the host's T-cells to cause tumour cell death. Mosunetuzumab, an anti-CD20 directed bispecific antibody was the first to be approved in follicular lymphoma, this has now been followed by quick approvals of Glofitamab and Epcoritamab in diffuse large B-cell lymphomas. This article reviews contemporary data and ongoing studies evaluating the role of bispecific antibodies in indolent b-cell non Hodgkin lymphomas. This is an area of active research and presents many opportunities in advancing the treatment of indolent lymphomas and potentially forge a chemo-free treatment paradigm in this condition.

Follicular lymphoma with a predominantly diffuse growth pattern with 1p36 deletion: a clinicopathologic analysis of eight cases

Objective: To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion. Methods: Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University (n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital (n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results: There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases. Conclusions: DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.

Epidemiological and histopathological aspects of lymphomas at Zinder National Hospital, Niger

Introduction: Lymphoma is a malignant lymphocytic hemopathy characterized by diffuse lymph node or extranodal infiltration. It occurs at all ages and poses a problem for us in terms of positive diagnosis and management. The objective of this study is to determine the epidemiological and histological aspects of lymphomas at the National Hospital Zinder. Methodology: This was a retrospective cross-sectional study of patient records collected for histopathological examination between November 2019 and December 2023. Included were patients of any age and of both sexes with their histopathological findings available. Results: Lymphomas accounted for 3.47% of all malignancies. The 40 to 60 age group was the most affected with 40.90% (n=9) of cases. The mean age was 45±20.05. The sex ratio was 1.75. Lymph node localization accounted for 68.18% (n=15) of cases. Histological examination confirmed the type of non-Hodgkin lymphoma in 77.27% (n=17) of cases. Phenotype B lymphoma predominates in 86.36% of cases (n=19). Our study showed that indolent lymphoma was the most common histological subtype of non-Hodgkin lymphoma in 31.82% (n=7) of cases. Hodgkin's lymphocytic depleted lymphoma was found in 13.63% (n=3) of cases. Conclusion: The analysis of these results allowed us to appreciate the extent of lymphomas and their multiple implications in our society by highlighting a high frequency of non-Hodgkin's lymphomas in the region.

Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma: a single-institution experience.

Extranodal marginal zone lymphoma (EMZL) encompasses 70% of cases of marginal zone lymphoma. Frontline bendamustine and rituximab (BR) were derived from trials involving other indolent non-Hodgkin's lymphomas. Only one trial has evaluated frontline BR prospectively in EMZL. This retrospective study reports outcomes among EMZL patients receiving frontline BR. Twenty-five patients were included with a median age of 69 years (40-81). Five (20.0%) patients had stage I/II disease, and 20 (80.0%) had stage III/IV disease. The median number of cycles was 6.0 (3.0-6.0). Maintenance rituximab was administered to 10 (41.7%) individuals. Overall response rate (ORR) was 100.0% (60.0% complete response, 40.0% partial response). Medians of overall survival and progression-free survival were not reached. The estimated 2-year progression-free survival was 85.2% and overall survival was 100.0%. Four (16.6%) patients had infections related to treatment; 3 (12.0%) transformed to diffuse large B-cell lymphoma; 5 (20.8%) had a relapse or progression of EMZL; and 3 (12.0%) died unrelated to BR. BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

The relation between hepatitis C viral infection and follicular lymphoma clinical course and outcome in a single-center study

Background Hepatitis C virus (HCV) infection has been related in the etiology of many lymphomas. Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. This comparative retrospective study aimed to identify a relationship between HCV and FL clinicopathologic features and neoplasm outcome. Patients and methods This study was conducted on 103 patients with FL who attended our institution during 2008–2019. Results The prevalence of patients with HCV FL was 49.5% and showed significant B symptoms (P=0.023), advanced stages (P=0.016) with higher Follicular Lymphoma International Prognostic Index scores (P=0.042). Progression-free survival showed no differences regarding the viral infection or histological grades. Median overall survival showed significant improvement with histological grades 1–2 (P&lt;0.0001), low Follicular Lymphoma International Prognostic Index, and HCV negative patients with FL, especially in the younger subgroup. Conclusion HCV positive patients with FL had a significantly more aggressive clinicopathological presentation and shorter overall survival. Thus, early virology screening and eradication of HCV infection in FL patients may improve the neoplasm course.

Clinical Outcome of Patients Receiving Rituximab in Combination with Bendamustine in Indolent B-cell Lymphomas: A Single-center Institutional Study.

Indolent non-Hodgkin's lymphomas (NHLs) are a diverse category of malignancies characterized by a chronic relapsing-remitting disease course. In the modern era, patients usually receive a combination of bendamustine plus rituximab as the initial therapy, otherwise known as an R-Benda regimen. While clinical trials have demonstrated R-Benda to be superior to other regimens, our study aims to provide insight into real-world outcomes of R-Benda therapy. We conducted a retrospective study for January 2015-July 2022 among patients receiving R-Benda for indolent NHLs at the Aga Khan University Hospital, Karachi, Pakistan. All patients underwent pre- and post-treatment assessment through positron emission tomography scan and computed tomography (CT) imaging. The response to treatment was assessed, and the overall survival (OS) and progression-free survival (PFS) were assessed using a Kaplan-Meier survival analysis. We enrolled 118 patients, out of which the majority were elderly males (64%). The 2-year follow-up rate was 76.3% (n = 90), and the median follow-up time was 29 months. The most common histopathology encountered was follicular lymphoma (52%) presenting with stage IV disease (56%). Approximately 73% experienced a complete metabolic response to the treatment. Of these, 31.4% subsequently experienced a relapse. In addition, 17.7% of patients underwent a partial response, while 7% had refractory disease. The mean OS was 140 months (95% CI: 120-160), while the lower quartile value was 50 months. On the other hand, the median PFS was 80 months (95% CI: 43-N/A). Our study demonstrated that patients on R-Benda had good clinical outcomes, with the vast majority living beyond 50 months. Moreover, 76.1% had no disease progression for the first 2 years. It adds to the existing body of literature that demonstrates that in real-world experience, the outcomes of R-Benda treatment are better than those reported by earlier randomized-control trials.

MYD88 mutation-positive indolent B-cell lymphoma with CNS involvement: Bing-Neel syndrome mimickers.

MYD88 p.L265P mutation occurs in over 90% of Waldenström's macroglobulinemia (WM), which is characterized by lymphoplasmacytic lymphoma (LPL) with monoclonal IgM. WM requires careful diagnosis due to overlapping features with other B-cell malignancies. Bing-Neel syndrome (BNS), a rare complication of WM, involves central nervous system (CNS) invasion. This report describes two cases of morphologically low-grade B-cell lymphoma in the bone marrow accompanied by the presence of a large B-cell lymphoma in the brain and a common MYD88 p.L265P mutation, which were eventually established as BNS mimickers. Although the two components in these cases showed the same identical light-chain restriction, different immunoglobulin heavy-chain rearrangement peaks indicated distinct lymphoma stem cells for CNS and bone marrow lesions. These clinical cases emphasize the challenges in diagnosing BNS. Based on the findings, biopsy is recommended for accurate identification of the clonal relationship and MYD88 mutation status.

Laboratórna diagnostika a liečba folikulového lymfómu

In the review article, we analyze the laboratory diagnostics follicular lymphoma (FL). We focus mainly on morphological diagnosis, which we also illustrate. Next, we approach the immunophenotypic, cytogenetic and molecular-biological diagnosis of this indolent lymphoma. We also point to the treatment of FL with a sketch of the current CAR T-cell therapy, which may be a hope for patients if previous procedures fail.

Current standard treatments and future outlook for follicular lymphoma

Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Survival outcomes for FL have improved since the introduction of anti-CD20 monoclonal antibodies, such as rituximab, and median overall survival has reached 15-20 years. However, FL is an incurable disease that subsequently progresses or relapses, and progression-free and overall survival tend to shorten with repeated relapses. For patients with limited-stage disease, radiation therapy is generally the treatment of choice and results in a median survival of approximately nearly 20 years. For advanced-stage patients with low tumor burden, watchful waiting continues to be the appropriate strategy at present. It remains unclear whether rituximab monotherapy might change this watchful waiting approach and result in a benefit from early intervention in patients with low tumor burden. For advanced-stage patients with high tumor burden, chemoimmunotherapy including rituximab or obinutuzumab followed by maintenance therapy is the standard treatment. For relapsed or refractory patients, treatment options such as chemoimmunotherapy, lenalidomide-rituximab, tazemetostat, chimeric antigen receptor T-cell therapies, and CD3/CD20 bispecific antibodies are available or in development. This review presents current standard treatments, recent advances, and future perspectives on the management of FL.