non-Hodgkin Research Articles

Extranodal Mantle Cell Lymphoma Presented as Bilateral Adrenal Masses on 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT.

Mantle cell lymphoma (MCL) is a rare type of B-cell non-Hodgkin lymphoma that commonly presents with constitutional symptoms, lymphadenopathy, and laboratory abnormalities. Although less common, extranodal involvement of MCL may be seen at initial presentation and most commonly occurs in the spleen, liver, bone marrow, and gastrointestinal tract. Adrenal involvement in MCL is extremely rare, and only a few cases have been reported in the literature. Herein, we present 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT findings of a unique case of primary extranodal MCL with gastric and adrenal involvement.

Diffuse large B-cell lymphoma: causes, pathology, and emerging treatments

Diffuse Large B-Cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma, characterized by aggressive behavior and significant heterogeneity. Understanding the causes, pathology, and emerging treatments for DLBCL is essential for improving patient outcomes. This review synthesizes current research on the causes, molecular pathology, and novel treatment strategies for DLBCL, drawing on data from recent clinical trials, genetic studies, and advancements in therapeutic approaches. Genetic mutations such as translocations involving BCL-2, BCL-6, and MYC genes, along with chronic infections and immune deficiencies, are key risk factors for DLBCL. Pathologically, DLBCL can be classified into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes, with differing prognoses. Emerging treatments include targeted therapies like BTK inhibitors (ibrutinib) and BCL-2 inhibitors (venetoclax), immunotherapies such as CAR T-cell therapy, and epigenetic modulators like HDAC inhibitors. Next-generation sequencing (NGS) is revolutionizing personalized medicine in diffuse large B-cell lymphoma (DLBCL) by enabling the identification of specific genetic mutations. Coupled with advancements in molecular pathology, NGS is driving the development of targeted therapies, immunotherapies, and epigenetic modulators. These innovations are collectively transforming the treatment landscape for DLBCL, offering more precise and effective therapeutic options tailored to individual genetic profiles. Continued research and clinical trials are essential for further refining these therapies and enhancing their effectiveness.

Pediatric B-cell Non-Hodgkin Lymphoma: The Impact of Therapy Response and Relapse on Outcome. A Single-center Analysis.

Pediatric patients with primary refractory or relapsed B-cell non-Hodgkin lymphoma (B-NHL) have highly unfavorable prognosis. In this study, we retrospectively analyzed outcomes in pediatric B-NHL patients treated in a single center in Poland from 1995 to 2022, with emphasis on therapy results in patients with progression or relapse. The primary objectives were a 5-year probability of overall survival (pOS) and a 5-year probability of event-free survival (pEFS). The secondary objectives involved the assessment of prognostic factors. A total of 76 children were eligible for the analysis. The 5-year pOS was 76.7%, and the 5-year pEFS was 72.9%. At diagnosis, elevated lactate dehydrogenase activity, the presence of B symptoms, bone marrow, skeletal or mediastinal involvement, and stage IV disease were associated with inferior outcomes. Nine children experienced progression and four relapse. The 5-year pOS for patients with progression was 38.1%. Two patients treated with hematopoietic stem cell transplantation (HSCT) as part of salvage therapy survived. However, only one out of seven patients who were treated without HSCT survived. The 5-year pOS was 0.0% in patients with relapsed disease. The most significant factor related to outcomes in pediatric B-NHL is therapy response, with a high mortality rate in children with refractory disease and relapse. There is no consensus on the salvage therapy approach; however, HSCT appears to be the optimal choice.

Recent Updates of PET in Lymphoma: FDG and Beyond

Lymphoma is one of the most common cancers worldwide, categorized into Hodgkin lymphoma and non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has become an essential imaging tool for evaluating patients with lymphoma in terms of initial diagnosis, staging, prognosis, and treatment response assessment. Recent advancements in imaging technology and methodologies, along with the development of artificial intelligence, have revolutionized the evaluation of complex imaging data, enhancing the diagnostic and predictive power of PET in lymphoma. However, FDG is not cancer-specific, but it primarily reflects glucose metabolism, which has prompted the investigation of alternative PET tracers to address this limitation. Novel PET radiotracers, such as fibroblast activation protein inhibitors targeting the tumor microenvironment, have recently shown promising results in evaluating various malignancies compared to FDG PET. Furthermore, with the rapid advancements in immunotherapy and the favorable imaging properties of 89Zr, immunoPET has emerged as a promising modality, offering insights into the functional and molecular status of the immune system. ImmunoPET can also facilitate the development of new antibody therapeutics and radioimmunotherapy by providing pharmacokinetic and pharmacodynamic data. This review provides comprehensive insights into the current clinical applications of FDG PET in lymphoma, while also exploring novel PET imaging radiotracers beyond FDG, discussing their mechanisms of action and potential impact on patient management.

Follicular lymphoma research: an open dialogue for a collaborative roadmap.

Follicular lymphoma (FL) is the second most common type of lymphoma (20% of all non-Hodgkin lymphomas), derived from germinal centre (GC) B cells, and is characterised by its significant clinical, prognostic and biological heterogeneity, leading to complexity in management. Despite significant biological investigation and indisputable clinical progress since the advent of the immunotherapy era more than 20 years ago, much remains to be done to understand and cure this lymphoma. Today, FL is metaphorically a giant puzzle on the table with patches of sky, landscape and foliage clearly appearing. However, many of the remaining pieces are held by various stakeholders (e.g. clinicians, pathologists, researchers, drug developers) without global agreement on what the gaps are, or any clear blueprint on how to solve the puzzle of understanding the heterogeneity of this disease and create curative and tailored therapies. With the advent of new investigation and drug technologies, together with recent advances in our capacity to manage big data, the time seems ripe for a change of scale. More than ever, this will require collaboration between and within all stakeholders to overcome the current bottlenecks in the field. As for every investigator, we acknowledge that this first draft is necessarily biased, incomplete and some FL expert readers might recognise some remaining gaps not addressed. We hope they will reply to make this effort a collaborative one to assemble all the pieces in the most ideal fashion. As such, this review intends to be a first step and an interactive platform to a collaborative roadmap towards better understanding and care of FL.

3D echocardiography and biomarkers for early diagnosis and prediction of chemotherapy induced right ventricular dysfunction in non-Hodgkin lymphoma patients

Abstract Background RCHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisone) use in non-Hodgkin's lymphoma (NHL) is limited by the risk of cardiotoxicity. Although the prognostic value of right ventricular (RV) function in mortality and morbidity has been well established, its involvement in chemotherapy-induced cardiotoxicity remains unclear. Aim To define new parameters able to detect early RV cardiotoxicity. Methods 51 patients (22 men, 61±14 years) with NHL scheduled for RCHOP, with three dimensional (3D) left ventricular (LV) ejection fraction (EF) >50%, were assessed at baseline, after 3rd and 6th cycle for right ventricular (RV) parameters: 3D EF, two dimensional (2D) global longitudinal strain (GLS) and free wall LS (FWLS), peak systolic annular velocity (S’), tricuspid annulus systolic excursion (TAPSE) and fractional area change (FAC). Biomarkers (troponin I, NT-pro-BNP) were measured. Cardiotoxicity was defined as LVEF reduction below 50% or preserved LVEF with LV LS decrease more than 15% from baseline. Results 15 (29%) of patients developed LV cardiotoxicity (group 1) while 36 did not fulfill this criteria (group 2). There was a significant reduction of RVEF, GLS, and FWLS, but not of RV S’, FAC, and TAPSE, starting with the 3rd cycle, with greater changes in group 1 vs. group 2 (see Table). RVEF reduction correlated with changes of FWLS, GLS, RV S’, and troponin (r=0.612, r=0.513, r=0.362, r=-0.358, respectively; all p<0.05). Reduction of FWLS after the 3rd cycle was the best independent predictor for RVEF decrease after the 6th cycle (R²=0.433, p<0.0001). FWLS decrease with more than 26% predicted cardiotoxicity after the 6th cycle (sensitivity of 81%; specificity of 78%). Conclusion 3D EF, 2D systolic deformation, and troponin I are able to detect early chemotherapy-induced right ventricular cardiotoxicity, and to predict further decline of RVEF in NHL patients. Thus, routine follow-up of RV function, along with the LV function, should be assessed during and after chemotherapy.RV parameters and troponin during RCHOP

Can the presence of aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma be used as a predictor of MACE?

Abstract Background Major adverse cardiovascular events (MACE), commonly defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and heart failure, represent a significant cause of mortality among patients with cancer. With increased rates of both cancer and cancer survivorship, the identification of new predictive markers for the development of MACE in this population is crucial for implementing effective preventive and risk-mitigation strategies. Purpose To determine whether the presence of calcifications in the coronary arteries (CAC) or aorta (CA) of lymphoma patients, as reported in standard-of-care PET-CT (Positron Emission Tomography-Computed Tomography) or chest CT (Computed Tomography) scan, can predict the occurrence of MACE. Methods A Retrospective analysis was conducted on a cohort of patients diagnosed with Hodgkin or non-Hodgkin lymphoma and treated with anthracycline-based chemotherapy. Patients were diagnosed from January 1, 2013, and followed through to June 30, 2023. The reference point for the study was the radiologist’s report of the PET-CT or chest CT conducted before the initiation of anthracycline therapy. Patients who did not undergo a PET-CT or CT before the start of treatment, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CA and CAC was associated with the development of MACE. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results 326 patients were included with a mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was reported in 75 patients (23%) and CA in 18 (6%). In the univariate regression model, a statistically significant association was found between the presence of both CA and CAC with the risk of MACE. CAC showed a stronger association with the development of MACE than CA (HR: 3.7 [1-7.9], p=0.0005 vs HR: 2.9 [1- 8.5], p=0.050). In multivariable analysis CAC emerged as the strongest predictor of MACE (HR: 2.9 [1.3 – 6.4], p=0.01), after accounting for hypertension, diabetes, dyslipidemia, and GFR <60 (Table 1), while the association with CA attenuated (HR: 2.01 [0.7-6.5], p=0.2010) and was no longer significant (Table 2). Conclusion CAC in the standard-of-care PET/-CT scans was a predictor of MACE in lymphoma patients treated with anthracyclines, while the association with CA weakened in multivariable analyses and was likely underpowered given the small number of patients with CA. If replicated, this finding warrants closer surveillance of this group of patients and can be considered as a non-invasive cardiovascular risk marker.

Asymptomatic presentation of diffuse large B-cell lymphoma as isolated submental lymphadenopathy

Non-Hodgkin lymphoma (NHL) is the most common type of lymphoma, Diffuse larger B-cell lymphoma (DLBCL) being most common type of NHL. Patients usually present at later stage with b-symptoms, lymphadenopathy and organomegaly. Isolated asymptomatic lymphadenopathy is a rare presentation. A 50-year-old female presented with complaints of swelling in the sub mental region. It increased in size over 1month without any associated local or systemic symptoms. On examination a firm, non-tender, mobile swelling of around 2×1.5 cm was present at sub mental region. Abdominal examination revealed no organomegaly. Blood picture- HB- 9.7 gm/dl, TLC- 5200/mm3, neutrophils/ lymphocytes/ eosinophil/ basophils-43.4/44.4/5.1/0.4 and Platelets-2.41 lakhs/mm3. Ultrasonography study was suggestive of necrotic lymph node. Fine needle aspiration cytology demonstrated nonspecific reactive lymphadenitis. After routine pre-operative workup patient was taken up for lymph node excision in elective OR under general anesthesia and the excised lymph node was sent for biopsy. A histopathological diagnosis of diffuse large B-cell lymphoma was made and confirmed with Immunohistochemistry (IHC), (CD20-diffuse positive; CD3-focal positive; Cyclin D-negative; BCL6-positive; CD10- focally positive). Post-operative hospital stay was uneventful. Our case was atypical with asymptomatic presentation with isolated lymphadenopathy with suspicious lymphocytosis. Diagnosis was only possible by histopathology.

Is there an association of anthracyclines with HFrEF and/or HFpEF in patients treated for breast cancer or lymphoma after 30 years of follow-up? Insights from the Rochester epidemiology project

Abstract Introduction Anthracyclines (ACs) have been identified as cardiotoxic drugs. They are associated with contractile dysfunction of the heart, which can manifest as heart failure. However, differentiating between HFrEF (left ventricular ejection fractions [LVEF] ≤40%) or HFpEF (LVEF >40%) has been overlooked. Purpose Using a retrospective cohort of patients with breast cancer (BC), Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and controls from the Rochester Epidemiology Project, we evaluated the association of ACs use with risk of HFrEF and/or HFpEF. Methods 797 subjects with BC, HL or NHL diagnosed from 1988 to 2010 were identified, 658 treated with ACs (ACs group) and 139 not treated with ACs (no-ACs group). Controls (n=1526) were subjects without cancer. The median (Q1, Q3) follow up was 11.5 years (7.4, 16.7). Cox proportional hazards regression was used to compare the risk of HFpEF and HFrEF in the three cohorts, adjustment for sex, CV comorbidities (type 2 diabetes [T2D], hypertension [HTN] and dyslipidemia), radiotherapy (RT), and ACs cumulative dose was performed. Results Baseline characteristics are shown in table 1. HFpEF occurred in 29/1526 subjects in the control group, 3/139 in the no-ACs group and in 14/658 in the ACs group. Compared to the control group, there was not an increased risk of developing HFpEF in the no-ACs group (HR 1.67, CI 95%: 0.5 – 5.53, p = 0.39) or in the ACs group (HR 1.83, CI 95%: 0.95 – 3.52, p = 0.06) (Figure 1). Compared with no-ACs group, the ACs group had a similar risk of developing HFpEF (HR 1.09, CI 95%: 0.3 – 3.87, p = 0.88). RT was associated with a lower risk of HFpEF (HR 0.21, CI 95%: 0.06 – 0.75, p = 0.01). In the multivariable analysis, T2D (HR 6.91, CI 95%: 3.07-15.56, p = <0.0001) was associated with higher risk of HFpEF. A cumulative dose of ACs > 250 mg/m2 was not associated with increased risk of HFpEF. HFrEF occurred in 25/1526 subjects in the control group, in 4/139 in the no-ACs group and in 31/658 in the ACs group. Compared to the control group, the ACs group had a significant increase in the risk of HFrEF (HR 4.77, CI 95%: 2.76 – 8.22, p < 0.0001), the no-ACs group did not (HR 2.81, CI 95%: 0.97 – 8.12, p = 0.055) (figure 2). RT was associated with lower risk of HFrEF (HR 0.29, CI 95%: 0.13 – 0.65, p = 0.002). In the multivariable analysis, ACs (HR 4.23, CI 95%: 2.4-7.47, p = < 0.0001) being male (HR 2.45, CI 95%: 1.43 – 4.15, p < 0.0001), smoking history (HR 2, CI 95%: 1.16 – 3.44, p < 0.01), and HTN (HR 3.23, CI 95%: 1.9 – 5.61, p < 0.0001), were associated with higher risk of HFrEF. A cumulative dose of ACs > 250 mg/m2 was not associated with increased risk of HFrEF. Conclusion To our knowledge this is the first study to differentiate between HFpEF and HFrEF in this cohort. ACs were not associated with increased risk of HFpEF. However, ACs were associated with increased risk of HFrEF, but not with a specific dose. These results should be validated in other population cohorts.

Artificial intelligence applied to electrocardiographic images for the risk stratification of cancer therapeutics-related cardiac dysfunction

Abstract Background Traditional risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability and affordability. Purpose To examine an artificial intelligence (AI)-enhanced electrocardiographic (AI-ECG) surrogate for imaging-based risk biomarkers, and its association with CTRCD. Methods Between 2013-2023, across 5 hospitals of a large U.S.-based health system, we identified patients with breast cancer or non-Hodgkin lymphoma (NHL) who received anthracyclines (AC) and/or trastuzumab (TZM), as well as a (negative) control cohort of patients receiving immune checkpoint inhibitors (ICI). We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to ECG images (≥0.1=positive screen) (ref 1) and explored the association between the model’s predictions and: i) global longitudinal strain (GLS) measurements within 15 days; ii) future CTRCD (defined as a new cardiomyopathy, heart failure, or left ventricular ejection fraction (LVEF) decrease to <50%), as well as a more specific secondary outcome of LVEF decrease <40%. In a negative control analysis of patients receiving ICI, we correlated baseline AI-ECG LVSD predictions with downstream myocarditis. Results Higher AI-ECG LVSD predictions were associated with progressively worse GLS (-18% [IQR: -20 to -17%] for AI-ECG predictions <0.1, to -12% [-15 to -9%] for ≥0.5, p<0.001, n=7,271) (A). In 1,308 patients receiving AC/TZM (age 59 [IQR 49-67] years, 999 [76.4%] women, 80 [IQR 42-115] follow-up months) a positive baseline AI-ECG LVSD screen was associated with higher incidence of CTRCD (n=404 events, adjusted HR 2.22 [95%CI: 1.63-3.02]) and/or LVEF <40% (n=72 events, adjusted HR 4.76 [95%CI: 2.62-8.66]) (B). In a negative control analysis of 2,056 patients receiving ICI (age 65 [IQR 57-73] years, 913 (44.4%) women, follow-up 63 [IQR 28-99] months) AI-ECG predictions were not associated with downstream myocarditis (adjusted HR 1.36 [0.47-3.93]). Conclusions AI applied directly to baseline ECG images may stratify the risk of CTRCD associated with anthracycline or trastuzumab exposure.

Prognostic factors and predictive models for primary pulmonary diffuse large B-cell lymphoma: a population-based analysis

ABSTRACT Background Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking. Methods We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions. Results A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL. Conclusion This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making.

A Rare Case of Signet Ring Cell Lymphoma and Review of the Literature

Signet ring cell lymphoma (SRCL) is a non-Hodgkin's lymphoma with a very rare variant. Although this morphology is frequently seen in follicular lymphoma, it can also be observed in the group of diffuse large B-cell lymphomas. A seventy-six year old woman with known diagnosis of gastric adenocarcinoma, tubular type, moderately differentiate presented with a lymphadenopathy with high FDG uptake (SUVmax: 21.3) in PET/CT during follow-up. A tru-cut biopsy was performed for histopathological diagnosis. Diffuse infiltrative singet ring neoplastic cells showed negativity for PanCK, CK7, CK20, S100, SMA, calretinin and vimentin. The panel was then expanded to include SRCL, a rare variant of lymphoma. Additional immunohistochemical evaluation revealed positivity for CD20, CD19, PAX-5 and Bcl-2. Ki-67 proliferation index was about 80%. CD3, CD30, Myc, Bcl-6, ALK, Cyclin-D1, CD23, CD10, CD21, and MUM-1 were negative. EBER was also negative by chromogen in situ hybridization (CISH). Based on these data, diffuse large B-cell lymphoma (DLBCL) was considered. We herein reported a case of signet ring cell lymphoma discussed its clinical and morphological features with regard to the literature.

The cyclin-G associated kinase (GAK) is a novel mitotic kinase and therapeutic target in diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma and the most frequently diagnosed hematologic malignancy in the United States. DLBCL exhibits significant molecular and clinical heterogeneity, and at least a third of patients are left uncured with standard frontline chemoimmunotherapy. As such, there is a critical need to identify novel targeted therapies to improve outcomes. We conducted a phenotypic screen of kinase inhibitors against DLBCL cell lines and non-malignant controls. We identified the cyclin G-associated kinase (GAK) as a tumor-selective, readily druggable target whose inhibition killed DLBCL cell lines, while sparing non-malignant blood cells. Upon investigation of GAK's cellular function, we discovered that inhibition results in G2/M-phase cell cycle arrest. Immunofluorescent confocal microscopy revealed significant chromosome misalignment and spindle distortion in DLBCL cells following GAK-inhibition, disrupting progression through mitosis. Analysis of RNA-seq data from clinical samples showed increased GAK expression associates strongly with RB1 deficiency in DLBCL cases, suggesting dependency on GAK for proper mitotic progression linked to retinoblastoma associated protein (RB) loss of function, a common DLBCL driver. In cell-cycle analyses and under microscopy, RB-deficient DLBCL cells treated with an exquisitely selective GAK inhibitor showed complete arrest at G2/M, pronounced distortion of mitotic spindles, and widespread chromosomal damage. Finally, in vivo studies of DLBCL xenograft-bearing NSG mice achieved a dramatic tumor-burden reduction in response to targeted GAK inhibition. These results reveal a novel cell cycle kinase suitable for therapeutic exploitation in DLBCL patients and linked to the common, undruggable biomarker of RB loss of function.

Impact of Malnutrition on the Length of Stay for Hospitalized Chimeric Antigen Receptor T-cell (CAR-T) Therapy Patients in the United States (2020).

Background Chimeric antigen receptor T-cell (CAR-T) therapy offers a promising treatment for certain malignancies but can be associated with complications. Malnutrition and cachexia are common in cancer patients and may worsen outcomes. This study investigated the impact of malnutrition on the length of hospital stay (LOS) in patients with hematologic malignancies undergoing CAR-T therapy. The analysis focused on different subpopulations, including those with acute lymphoblastic leukemia (ALL), multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), and non-Hodgkin lymphoma (NHL) excluding DLBCL. Methods Utilizing the 2020 National Inpatient Sample (NIS) data, we performed survey-based mean estimation analyses for LOS across various subpopulations of CAR-T therapy patients. These subpopulations were defined by specific diagnoses: ALL, myeloma, DLBCL, and NHL excluding DLBCL. We compared the LOS between patients with and without malnutrition using STATA accounting for the complex survey design. Cachexia was included as disease-induced malnutrition. Results The total CAR-T population used for analyses included 439 patients, and malnutrition was present in 50 (11.39%). The overall CAR-T population demonstrated a significantly longer LOS for patients with malnutrition (30.92 days, 95% CI: 24.30 to 37.54) compared to those without malnutrition (17.97 days, 95% CI: 15.48 to 20.46, p = 0.0002). This trend held true across subgroups. Specifically, the ALL population had a significantly longer LOS with malnutrition (45.25 days, 95% CI: 35.46 to 55.04) compared to non-malnourished patients (27.58 days, 95% CI: 16.74 to 38.42, p = 0.0279). For the DLBCL population, the mean LOS was 24.47 days (95% CI: 19.22 to 29.71) with malnutrition and 17.17 days (95% CI: 13.29 to 21.04, p = 0.0161) without malnutrition. The NHL population excluding DLBCL exhibited a mean LOS of 33.86 days (95% CI: 22.66 to 45.07) for malnourished patients and 17.44 days (95% CI: 14.76 to 20.11, p = 0.0055) for non-malnourished patients. The myeloma population showed a similar trend although not statistically significant, with a mean LOS of 39.00 days (95% CI: -3.54 to 81.54) for malnourished patients and 18.03 days (95% CI: 15.02 to 21.03, p = 0.3337) for non-malnourished patients. These findings highlight significant variations in LOS across different CAR-T-treated cancer subtypes, emphasizing the impact of malnutrition on healthcare resource utilization in oncology. Conclusion Malnutrition is associated with a significantly longer hospital stay among patients undergoing CAR-T therapy. This trend is consistent across various subpopulations, including those with ALL, DLBCL, and NHL (excluding DLBCL). While the impact of malnutrition on LOS was not statistically significant in the myeloma population, this could potentially be attributed to the smaller sample size in this group. Overall, these findings underscore the critical role of nutritional status in managing patients undergoing CAR-T therapy. Future studies should investigate the most effective methods for identifying and treating malnutrition in this patient population to reduce hospital stays and optimize overall patient care.

Clinical characteristics and prognosis of bloodstream infections with carbapenem-resistant Gram-negative organisms in patients with hematological malignancies: A multicenter case-control study in China

To investigate clinical characteristics of hematological malignancy (HM) patients with carbapenem-resistant gram-negative organism (CRO) bloodstream infections (BSI) in China, and to elucidate the prognostic risk factors of CRO BSI. We conducted a multicenter case-control study of 201 HM patients with CRO BSI between 2018-2020. Antimicrobial susceptibility testing and whole genome sequencing were performed for CRO isolates. Independent risk factors for 28-day crude mortality of were analyzed using Cox proportional hazards regression models. The subgroups of major species were also evaluated. The pathogens responsible for CRO BSI in HM patients dominated by ST11 CRKP, ST167 CREC and ST463 CRPA. Most isolates produced carbapenemases with KPC and NDM being the main. CRO isolates had resistance rates to conventional antimicrobials ranging from 55%-100% and poor susceptibility to novel antimicrobials related to carbapenemases and species. The 28-day crude mortality was 24.2%. Non-Hodgkin lymphoma, heart disease, blaKPC-2 positive, empirical antibiotic therapy with linezolid, Pitt bacteremia score >3.5 were risk factors for 28-day mortality and appropriate definitive antibiotic therapy, tigecycline-containing therapy and aminoglycoside-containing therapy were protective factors. blaKPC-2 positive in CRKP and ST463 in CRPA were associated with Pitt bacteremia score > 3.5. Solid tumor and other site infections before BSI were risk factors for ST463 CRPA BSI and Pulmonary infection before BSI was risk factor for KPC-KP BSI. The antimicrobial resistance of CRO isolates for BSI in HM patients is critical. HM patients with CRO BSI should be treated with appropriate definitive antibiotic therapy based on early clarification of pathology and their antimicrobial susceptibility.

Non-Invasive Imaging Including Line-Field Confocal Optical Coherence Tomography (LC-OCT) for Diagnosis of Cutaneous Lymphomas.

Background/Objectives: Primary cutaneous lymphomas (PCL) are a heterogeneous group of non-Hodgkin lymphomas arising from malignant T (CTCL) or B (CBCL) cells, often mimicking other skin conditions. Recently, non-invasive diagnostic imaging modalities, including dermoscopy, Reflectance Confocal Microscopy (RCM), and Line-field Optical Coherence Tomography (LC-OCT), have become increasingly important, supporting clinicians in clinical practice. Hence, our study aimed to describe dermoscopic, RCM, and LC-OCT features of PCL and to explore their role in PCL management. Methods: Between December 2022 and January 2024, 40 lesions of 25 patients with PCL were retrospectively analyzed at the Dermatologic Unit of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, and RCM criteria were assessed and their frequencies were calculated. Results: At dermoscopy, CTCL lesions were characterized by pinkish structureless areas (58,6%) and homogeneous distributed dotted vessels (35,7%), whereas 57.1% of CBCL presented with orange-yellow structureless areas. Considering CTCL, lymphocytes in the epidermis, dermal-epidermal junction, and dermis were detected by LC-OCT in 73.1%, 66.7%, and 51.9% and by RCM in 72.2%, 55.6%, and 61.1% of cases, respectively. The detection of lymphocytes was more precise using RCM than LC-OCT in CTCL (p < 0.001). Dermal infiltration of medium-reflective cells was visible in 80% and 40% of CBCL cases by LC-OCT and RCM, respectively. Conclusions: Non-invasive imaging techniques may support clinicians in managing PCL; however, further studies are mandatory in this field.

Preclinical Aspects of [89Zr]Zr-DFO-Rituximab: A High Potential Agent for Immuno-PET Imaging.

An early diagnosis of cancer can lead to choosing more effective treatment and increase the number of cancer survivors. In this study, the preparation and preclinical aspects of [89Zr]Zr-DFO-Rituximab, a high-potential agent for PET imaging of Non- Hodgkin Lymphoma (NHL), were evaluated. DFO was conjugated to rituximab monoclonal antibody (mAb), and DFO-rituximab was successfully labeled with zirconium-89 (89Zr) at optimized conditions. The stability of the complex was assessed in human blood serum and PBS buffer. Radioimmunoreactivity (RIA) of the radioimmunoconjugate (RIC) was evaluated on CD20-overexpressing Raji cell line and CHO cells. The biodistribution of the radiolabeled mAb was studied in normal and tumorbearing rodents. Finally, the absorbed dose in human organs was estimated. The radiolabeled compound was prepared with radiochemical purity (RCP) >99% (RTLC) and a specific activity of 180±1.8 GBq/g. The RCP of the final complex PBS buffer and human blood serum was higher than 95%, even after 48 h post incubation. The RIA assay demonstrated that more than 63% of the radiolabeled compound (40 ng/ml, 0.5 mL) was bound to 5×106 Raji cells. The biodistribution of the final product in tumor-bearing mice showed a high accumulation of the RIC in the tumor site in all intervals post-injection. Tumor/ non-target ratios were increased over time, and longer imaging time was suggested. The dosimetry data indicated that the liver received the most absorbed dose after the complex injection. [89Zr]Zr-DFO-Rituximab represents a significant advancement in the field of oncological imaging and offers a robust platform for both diagnostic and therapeutic applications in the management of B-cell malignancies.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a 15-Year-old male presenting with orofacial Swelling

BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of non-Hodgkin lymphoma that primarily affects subcutaneous tissues. Its occurrence in the orofacial region is exceptionally uncommon, presenting diagnostic challenges due to symptom overlap with more prevalent orofacial condition.Case presentationThis report details the case of a 15-year-old male who presented with persistent left-sided facial swelling, initially misdiagnosed as facial cellulitis. Diagnostic complexity arose from the similarity of symptoms to common orofacial diseases. Comprehensive diagnostic approaches, including liquid-based thin-layer cytometry, immunohistochemistry, and advanced imaging, were pivotal in identifying SPTCL. The recurrence of symptoms following the cessation of dexamethasone treatment indicated hormone dependency. Surgical intervention and subsequent histopathological analysis confirmed SPTCL, with immunohistochemical profiling playing a critical role in the definitive diagnosis. The patient’s management involved a multidisciplinary approach, leading to a referral to a hematology specialist and subsequent favorable outcomes.ConclusionsThis case underscores the diagnostic challenges of orofacial lymphomas such as SPTCL and highlights the necessity for early, accurate pathological diagnosis. It emphasizes the role of advanced diagnostic techniques and the importance of a comprehensive, multidisciplinary approach in the management of such rare cases. This report contributes to the limited but growing body of literature on SPTCL in the orofacial region, providing insights for clinicians in similar future cases.

Gene expression profiling in B-cell non-Hodgkin lymphomas

Abstract BACKGROUND: Gene expression profiling has become a fundamental tool in cancer diagnosis and management. B-cell non-Hodgkin lymphoma (B-NHL) is a group of malignant neoplasms originating from the lymphoid tissues, mainly the lymph nodes and the gene expression technique was used to unravel its complexity and aid in clinical decision-making. OBJECTIVES: The aims of this study were to find the significance of gene expression profiling focusing on colony-stimulating factor 1 receptor (CSF1R), myeloid differentiation factor 88 (MyD88), and tumor necrosis factor-α (TNF-α) as a promising approach in B-NHL diagnosis and their comparison with healthy controls. PATIENTS, MATERIALS AND METHODS: The current clinical prospective study was mediated from June 1, 2021, to December 30, 2022, of NHL patients in Kurdistan, Iraq. Seventy-three patients were recruited from Nanakali Hospital for Blood Diseases and Cancer, Erbil. The integration of gene expression biomarkers uses quantitative real-time polymerase chain reaction technique to diagnose B-NHL. Specifically, we focused on three key genes MyD88, TNF, and CSF1R whose expression profiles were analyzed in B-NHL patients and controls. We leveraged a dataset to explore gene expression patterns in B-NHL and applied classification algorithms to distinguish between B-NHL patients and controls. RESULTS: The initial results show the overall lower CSF1R expression in B-NHL as compared to the controls and a significant reduction in CSF1R expression in females (≤50 years and &gt;50 years). The result considers lower CSF1R expression in B-NHL males (≤50 years) and higher but not significant in males (&gt;50 years). CONCLUSIONS: These B-NHL-expressed genes may be considered potential diagnostic markers with their meaningful comparisons to control groups, and they could be proposed to guide the management of patients and facilitate their stratification into clinical trials.

Primary Mediastinal Large B-cell Lymphoma – A Case Report

AbstractPrimary mediastinal large B-cell lymphoma (PMBL) is an uncommon and aggressive subtype of non-Hodgkin large B-cell lymphoma that affects patients in the third and fourth decades of life. The objective of the present report is to describe the case of a male patient admitted to the emergency room with symptoms of dyspnea associated with signs of superior vena cava syndrome. The imaging exams revealed two masses in the mediastinum; the definitive diagnosis, established through an anatomopathological examination and immunohistochemistry, was of PMBL, and the patient was referred for chemotherapy.