Inflammatory Back Pain and Psoriasis: Expecting Spondyloarthritis, Discovering Lymphoma.

Inflammatory back pain is a characteristic of spondyloarthritis. It is not, however, an exclusive symptom of inflammatory rheumatic diseases as it can also be associated with non-inflammatory entities. Infrequently, the etiology can be found in neoplastic conditions such as malignant lymphoma. Even in the presence of comorbidities indicatory of underlying rheumatic disease, like psoriasis vulgaris, the clinician should not be led astray. It is essential to pay attention to contradictory findings, as treatment crucially differs depending on diagnosis. Herein, we report on a psoriasis patient who presented with characteristic inflammatory back pain and deceptive imaging results. While the patient was initially thought to suffer from an inflammatory rheumatic disease with axial involvement, it was the accompanying atypical circumstances, particularly her age, that instantly challenged the diagnosis of axial psoriatic arthritis. She was eventually diagnosed with stage IV follicular lymphoma that manifested with rare and exclusively extranodal lesions and spondyloarthritis-like morphology. This case effectively demonstrates the importance of a thorough diagnostic workup and how certain clinical factors, such as the patient's age, should be considered when confronted with inflammatory back pain.

Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity.

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

Review of computer-assisted diagnosis model to classify follicular lymphoma histology.

The field of image processing is experiencing significant advancements to support professionals in analyzing histological images obtained from biopsies. The primary objective is to enhance the process of diagnosis and prognostic evaluations. Various forms of cancer can be diagnosed by employing different segmentation techniques followed by postprocessing approaches that can identify distinct neoplastic areas. Using computer approaches facilitates a more objective and efficient study of experts. The progressive advancement of histological image analysis holds significant importance in modern medicine. This paper provides an overview of the current advances in segmentation and classification approaches for images of follicular lymphoma. This research analyzes the primary image processing techniques utilized in the various stages of preprocessing, segmentation of the region of interest, classification, and postprocessing as described in the existing literature. The study also examines the strengths and weaknesses associated with these approaches. Additionally, this study encompasses an examination of validation procedures and an exploration of prospective future research roads in the segmentation of neoplasias.

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.

Efficacy and safety of MIL62, a novel glycoengineered type â ¡ anti-CD20 monoclonal antibody, combined with lenalidomide in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma: a multicentre, single-arm, phase 1b/2 trial.

Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1-3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2-8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2-22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301). Findings: Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0-12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54). Interpretation: MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024). Funding: Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Long-Term Remission with Novel Combined Immune-Targeted Treatment for Histiocytic Sarcoma Accompanied by Follicular Lymphoma: Case Report and Literature Review.

Histiocytic sarcoma (HS) is an extremely rare but aggressive hematopoietic malignancy, and the prognosis has been reported to be rather unfavorable with a median overall survival of merely 6 months. We presented a 58-year-old female patient complaining of abdominal pain and fever, who was admitted to our institution in September 2021. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan showed enlargement of generalized multiple lymph nodes. Subsequently, laparoscopic retroperitoneal lesion biopsy and bone marrow aspiration were performed. The pathological findings indicated the diagnosis of HS concurrent with follicular lymphoma. The immunohistochemistry (IHC) staining of the tumor lesion revealed a high expression of CD38 and PD-L1 proteins. Furthermore, KRAS gene mutation was identified by means of next-generation sequencing. The patient exhibited poor treatment response to both first- and second-line cytotoxic chemotherapies. Therefore, she underwent six cycles of Daratumumab (anti-CD38 monoclonal antibody), Pazopanib (multi-target receptor tyrosine kinases inhibitor) combined with third-line chemotherapy, followed by involved-site radiotherapy and maintenance therapy with the PD-1 inhibitor Tislelizumab. Long-term partial remission was finally achieved after multi-modality treatment. Duration of remission and overall survival reached 22 and 32 months, respectively. Our case indicated that immuno-targeted treatment coupled with chemotherapy and radiotherapy might constitute a potential therapeutic option for HS.

A Radiation-Free Approach Based on the Whole-Body MRI Has Shown a High Level of Accuracy in the Follow-Up of Lymphoma Patients-A Single Center Retrospective Study.

Background: Recurrence, even after years from the last treatment, characterizes lymphoproliferative disorders. Therefore, patients in complete remission from the disease should be followed up with periodic clinical checks. There is not a consensus on the role of imaging for this aim, because the radiological techniques used at the time of diagnosis expose patients to a risk of ionizing radiation damage. Whole-body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI-DWI) has given similar results to gold standard techniques in detecting lymphoma in the involved sites without ionizing radiation. In this retrospective real-life study, we aimed to assess the accuracy of WB-MRI-DWI during follow-ups of lymphoma patients in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Methods: Lymphoma patients who were subject to at least one WB-MRI-DWI during follow-up between February 2010 and February 2022 were enrolled. Results: Based on our investigation, the calculated sensitivity of WB-MRI-DWI was 100% (95% CI: 99.4-100.0), the specificity was 98.6% (95% CI: 97.4-99.3), PPV was 79% (95% CI: 75.9-81.9), and NPV was 100% (95% CI: 99.4-100.0). Conclusions: Despite the possibility of poor patient compliance and the identification of false positives, WB-MRI-DWI examination demonstrated an excellent sensitivity in ruling out the disease relapse.

Recent updates on treatment options for primary follicular lymphoma of the gastrointestinal tract.

BACKGROUND: Primary gastrointestinal follicular lymphoma is a subtype of follicular lymphoma that originates directly from the gastrointestinal tract. Pathologically, it exhibits substantial similarities with the secondary gastrointestinal involvement observed in nodal follicular lymphoma. However, primary gastrointestinal follicular lymphoma presents clinically distinct features, necessitating divergent considerations in treatment selection compared with nodal follicular lymphoma. AREAS COVERED: This narrative review focused on recent articles (2018-2023) regarding the long-term prognosis and treatment options for gastrointestinal follicular lymphoma. In addition, a brief overview of gastrointestinal follicular lymphomas is provided. EXPERT OPINION: Patients with primary gastrointestinal follicular lymphoma often present with a low tumor burden. Lymphoma lesions typically remain asymptomatic for several years or may undergo spontaneous regression without immediate treatment. Therefore, a 'watch and wait' approach is justified. Conversely, when large tumor masses are identified in the gastrointestinal tract, the potential for tumor bleeding or intestinal obstruction requires timely therapeutic interventions.

Quality of Life Evaluation in Patients with Follicular Cell Lymphoma: A Real-World Study in Europe and the United States.

INTRODUCTION: Follicular lymphoma (FL) is an indolent subtype of non-Hodgkin's lymphoma (NHL), characterized by a long natural course of remissions/relapses. We aimed to evaluate real-world quality of life (QoL) in patients with FL, by line of therapy (LOT), and across countries. METHODS: Data were drawn from the Adelphi FL Disease Specific Programme™, a cross-sectional survey of physicians and their patients in Europe [France, Germany, Italy, Spain, the United Kingdom (UK)], and the United States (US) from June 2021 to January 2022. Patients provided demographics and patient-reported outcomes via the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30). Bivariate analysis assessed QoL versus NHL, across LOT [first line (1L), second line (2L), third line or later (3L+)] and country. RESULTS: Patients (n = 401) had a mean [standard deviation (SD)] age of 66.0 (9.24) years, 58.1% were male, and 41.9%/22.9% were Ann Arbor stage III/IV. Patients with FL mean EORTC global health status (GHS)/QoL, nausea/vomiting, pain, dyspnea, appetite loss, and diarrhea scores were statistically significantly worse (p < 0.05) versus the NHL reference values. Mean (SD) GHS/QoL worsened from 1L [56.5 (22.21)] to 3L+ [50.4 (20.11)]. Physical and role functioning, fatigue, pain, dyspnea, and diarrhea scores also significantly worsened across later LOTs (p < 0.05). Across all functional domains, mean scores were significantly lower (p < 0.05) and almost all symptom scores (excluding diarrhea) were significantly higher (p < 0.05) for European versus US patients. CONCLUSIONS: Patients with FL at later LOTs had significantly worse scores in most QoL aspects than earlier LOTs. European patients had significantly lower functioning and higher symptom burden than in the US. These real-world findings highlight the need for novel FL therapies that alleviate patient burden, positively impacting QoL.

There is little information about the effects of follicular lymphoma and treatments on quality of life as assessed by patients. We surveyed doctors and their patients with follicular lymphoma across France, Germany, Italy, Spain, the United Kingdom, and the United States (US), and asked patients to complete a form reporting their quality of life. A total of 401 patients were included.In general, patients with follicular lymphoma treated across all lines of treatment had worse quality of life and symptoms of nausea and vomiting, pain, shortness of breath, appetite loss, and diarrhea compared to a reference group of patients with non-Hodgkin's lymphoma (NHL). Overall quality of life and physical, role, and social functioning of patients with follicular lymphoma worsened from the first to the third line of treatment. Fatigue, pain, dyspnea, and diarrhea symptom scores also worsened across the lines of therapies. European patients had worse quality of life, functioning, and symptoms compared to US patients. Better treatments are needed to improve symptoms, functions, and quality of life for patients with follicular lymphoma.

Exposure to obinutuzumab does not affect outcomes of SARS-CoV-2 infection in vaccinated patients with newly diagnosed advanced-stage follicular lymphoma.

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

A phase I trial of vaccination with lethally irradiated lymphoma cells admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells for the treatment of follicular lymphoma.

Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.

Symptomatic Follicular Lymphoma: Complete Remission After Chemoimmunotherapy with Bendamustine-Rituximab.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in Western countries after diffuse large B-cell lymphoma. Most patients with FL present with asymptomatic disease. Survival rates have been rising over time mainly due to advancing therapeutic strategiesA-51-year-old male with a history of well-controlled diabetes mellitus treated with insulin presented to the policlinic of hematology-medical oncology with worsening right inguinal lymphadenopathy for >3 months. He had no complaints of prolonged fever, night sweat, or weight loss. Initial physical examination revealed a healthy male with bulky right inguinal lymphadenopathy. The patient was then referred to a surgeon, and excisional biopsy of the enlarged right inguinal lymph nodes was performed. Therefore, stage II bulky symptomatic low-grade FL was established. We administered chemoimmunotherapy with rituximab and bendamustine every 3 weeks for six cycles. The patient tolerated the treatment well and completed six cycles of chemoimmunotherapy, and the follow-up FDG PET/CT showed complete remission of the disease.The patient achieved complete remission after series of chemoimmunotherapy with Bendamustine-Rituximab. Future assessment is still required for this patient to ensure the remission status of the lymphoma.

Subsequent Malignancies After CD19-Targeted Chimeric Antigen Receptor T Cells in Patients With Lymphoma.

Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL. We retrospectively studied 355 patients from 2 different medical centers treated with four different CAR T cell products from 2016 to 2022. The overall cumulative incidence for subsequent malignancies at 36 months was 14% (95% CI: 9.2%, 19%). Subsequent malignancies were grouped into 3 primary categories: solid tumor, hematologic malignancy, and dermatologic malignancy with cumulative incidences at 36 months of 6.1% (95% CI: 3.1%-10%), 4.5% (95% CI: 2.1%-8.1%) and 4.2% (95% CI: 2.1%-7.5%) respectively. Notably, no cases of T cell malignancies were observed. In univariable analysis, increasing age was associated with higher risk for subsequent malignancy. While the overall benefits of CAR T products continue to outweigh their potential risks, more studies and longer follow ups are needed to further demonstrate the risks, patterns, and molecular pathways that lead to the development of subsequent malignancies.

Prolonged water-only fasting in the management of low-grade follicular lymphoma: a case series.

BACKGROUND: Follicular lymphoma typically follows an indolent and relapsing course often requiring several treatment cycles to achieve remission. Some patients opt to use complementary and alternative therapies particularly when observation is a treatment option. CASE PRESENTATION: Here we present a case series of three patients, a 50-year-old, White, Hispanic female, 56-year-old, White, non-Hispanic male, and 49-year-old, White, non-Hispanic male, who elected to undergo one or more prolonged water-only fasting and refeeding interventions to manage low to intermediate grade follicular lymphoma. Fasting was well tolerated in each patient. Each patient also experienced a reduction in the size and avidity of hypermetabolic lymph nodes as independently determined by their respective oncologists. CONCLUSION: The reported cases demonstrate positive outcomes in low-grade follicular lymphoma coinciding with prolonged water-only fasting and exclusively whole-plant-food dietary interventions. These findings highlight the potential of such interventions and warrant further exploration through preliminary observational research.

Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on Behalf of the American Society of Transplantation and Cellular Therapy and the European Society of Blood and Marrow Transplantation.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project.

Time to optimize vaccination strategies in blood cancer patients.

Immune response to vaccinations is dampened in patients with indolent lymphomas due to disease and treatment-related factors. The study by Lim et al. demonstrated impaired humoral response but intact cellular response to the SARS-CoV2 vaccine in patients with follicular lymphoma receiving front-line therapy. The results highlight the importance of several factors in predicting immune response to vaccination and provide estimates of immune response for different clinical scenarios and treatment points. Commentary on: Lim et al. Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19562.

[The Reduction of CD4+ T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy].

OBJECTIVE: To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. METHODS: The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. RESULTS: The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OS（P ＞0.05）. Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. CONCLUSION: The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.