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To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS).We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015.We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS.The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.

Lung cancer is a common cancer in people living with HIV, but the risk of cancer in this group has not been investigated for over a decade. We investigated trends in relative and absolute risk of lung cancer among people living with HIV of various age groups in the USA.In this population-based registry linkage study, we used 2001-16 data from the HIV/AIDS Cancer Match study, which links data from HIV and cancer registries from 13 regions in the USA. We included non-Hispanic White, non-Hispanic Black, and Hispanic individuals living with HIV aged 20-89 years in our study population. Average annual percentage changes in lung cancer rates were estimated with multivariable Poisson regression, and standardised incidence ratios (SIRs) and excess absolute risks were estimated comparing people living with HIV with the general US population. We used non-parametric cumulative incidence curves to estimate the 5-year cumulative incidence of lung cancer and two AIDS-defining cancers (non-Hodgkin lymphoma and Kaposi sarcoma).There were 3426 lung cancers in 4 310 304 person-years of follow-up in our study population. Age-standardised lung cancer incidence rates in people living with HIV declined by 6% per year (95% CI -7 to -5) during 2001-16, with greater declines in the 20-29 age group (-11%, -16 to 6) than in the older age groups (eg, -3% [-6 to 1] in those aged 70-89 years). During 2013-16, the SIR of lung cancer in people living with HIV was 2·01 (95% CI 1·52 to 2·61) in those aged 40-49 years, and 1·31 (1·12 to 1·52) in those aged 60-69 years, whereas the excess absolute risk among people living with HIV was 11·87 (3·95 to 21·89) per 100 000 person-years for those aged 40-49 years and 48·23 (6·88 to 95·47) per 100 000 person-years for those aged 60-69 years. Beginning in 2011, the 5-year cumulative incidence for lung cancer (1·36%, 95% CI 1·17 to 1·53) surpassed that of Kaposi sarcoma (0·12%, 0·06 to 0·17) and non-Hodgkin lymphoma (0·45%, 0·35 to 0·56) for people living with HIV aged 60-69 years.Between 2001 and 2016, the risk of lung cancer decreased for people living with HIV aged 20-69 years, but remained substantially elevated compared with the general population, probably due to a combination of smoking and immunosuppression. For people living with HIV aged 60 years and older, the risk of lung cancer exceeds that of two of the most common AIDS-defining cancers, highlighting the importance of lung cancer among the growing older population of people living with HIV.Intramural Research Program of the US National Cancer Institute.

Mediastinal radiation is associated with increased risk of myocardial infarction (MI) among non-Hodgkin lymphoma (NHL) survivors.To evaluate how preexisting cardiovascular risk factors (CVRFs) modify the association of mediastinal radiation and MI among a national population of NHL survivors with a range of CVRFs.Using Danish registries, we identified adults diagnosed with lymphoma 2000-2010. We assessed MI from one year after diagnosis through 2016. We ascertained CVRFs (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at lymphoma diagnosis. We used multivariable Cox regression to test the interaction between preexisting CVRFs and receipt of mediastinal radiation on subsequent MI.Among 3151 NHL survivors (median age 63, median follow-up 6.5 years), 96 were diagnosed with MI. Before lymphoma, 32% of survivors had ≥1 CVRF. 8.5% of survivors received mediastinal radiation. In multivariable analysis, we found that mediastinal radiation (HR = 1.96; 95% CI = 1.09-3.52), and presence of ≥1 CVRF (HR = 2.71; 95% CI = 1.77-4.15) were associated with an increased risk of MI. Although there was no interaction on the relative scale (Patients with CVRFs have an importantly higher risk of subsequent MI if they have mediastinal radiation. Routine evaluation of CVRFs and optimal treatment of preexisting cardiovascular disease should continue after receiving cancer therapy. In patients with CVRFs, mediastinal radiation should only be given if oncologic benefit clearly outweighs cardiovascular harm.

Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who achieve progression-free survival (PFS) at 24 months (PFS24) after immunochemotherapy (IC) have excellent overall survival (OS) comparable to that of the age- and sex-matched general population. However, a similar landmark has not been established for patients with relapsed or refractory (RR) DLBCL following frontline IC who are subsequently treated with salvage therapy followed by autologous stem cell transplantation (ASCT). To evaluate the role of PFS24 as a landmark after ASCT in patients with RR DLBCL, we identified patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic between July 2000 and December 2017 and University of Iowa between April 2003 and April 2020 from institutional lymphoma and transplantation databases. Clinical characteristics, treatment information, and outcome data were abstracted. PFS, OS, and post-ASCT relapse survival (PRS) were analyzed using Kaplan-Meier method, and cumulative incidences of relapse versus nonrelapse mortality and different causes of death were compared accounting for competing events. A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow-up of 8.0 years (95% confidence interval [CI], 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, the post-ASCT relapse rate was much higher than the nonrelapse mortality rate (48.1% versus 9.1% at 5 years). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and nonrelapse mortality were similar (14.8% and 12.3% at 5 years). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma-related and -unrelated death rates were similar after achieving PFS24. For all patients who had a post-ASCT relapse, median PRS was 0.7 (95% CI, 0.5-0.9) year, and late relapse (2 versus ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] versus 0.5 [0.3-0.7] years, P.001). The study establishes PFS24 as an important landmark associated with post-ASCT outcomes in patients with RR DLBCL after frontline IC.

We estimated years of life lost (YLLs) to all causes of death and YLL lost to cancer among persons with HIV (PWH) in the United States.Linked HIV and cancer registry data from the HIV/AIDS Cancer Match Study were used to identify incident cancers and deaths among PWH in 11 regions of the United States during 2006-2015.Mean YLL (MYLL) to all causes of death and MYLL to cancer during 2006-2015 were derived from the restricted mean survival estimated from Cox proportional hazards regression models. MYLLs were then upweighted to the national population of PWH to obtain all-cause total YLL (TYLL) and cancer-related TYLL in the United Staets during 2006-2015.Among 466 234 PWH in the study population, 25 772 (5.5%) developed cancer during 2006-2015. Nationally, an estimated 134 986 years of life were lost to cancer of all types during 2006-2015 among PWH, representing 9.6% of TYLL to all causes. Non-Hodgkin lymphoma (NHL), Kaposi sarcoma, anal cancer, and lung cancer were the four largest cancer contributors (45% of TYLL to cancer). The largest fraction of TYLL occurred among back PWH, MSM, and PWH aged 40-59 years old.PWH have higher mortality rates after developing cancer. NHL, Kaposi sarcoma and anal and lung cancers were large contributors to YLL to cancer in the United States population of PWH, highlighting opportunities to reduce cancer mortality through improved access to antiretroviral treatment, prevention, and screening.

Radiation therapy can be used with curative intent in patients with low-grade orbital non-Hodgkin's lymphoma (NHL) stages IE and IVE (limited to the bilateral orbits). This study evaluated local control and survival outcomes of patients with unilateral or bilateral orbital lymphoma treated in a provincial population.The study subjects were 176 patients with low-grade orbital or conjunctival lymphoma referred for management from 1980 to 2016. Demographic, tumour and treatment characteristics were abstracted by chart review. Recurrence-free survival (RFS) and overall survival were assessed with competing risks analysis and Gray's test.The median follow-up was 8.5 years (range 0.4-29.5 years). The median age at diagnosis was 65 years (range 20-97 years). The most common histological subtype was mucosa-associated lymphoid tissue (MALT) (73%). Stage IVE accounted for 20.5% of the cohort. Orbital radiation therapy was used in 122 patients with stage IE (87%) and 12 patients with stage IVE (28%). The median dose was 25 Gy (range 2-35 Gy). Other treatments were antibiotics (seven patients), chemotherapy (10 patients), radioimmunotherapy (six patients), surgery (three patients) and observation (16 patients). Within the group treated with orbital external beam radiation therapy (EBRT) there were no local recurrences. Among those with stage IE NHL, EBRT was associated with improved local RFS (P ≤ 0.001) but did not have an impact on contralateral or distant RFS. In patients with stage IVE NHL limited to the bilateral orbit, bilateral EBRT was associated with improved RFS (P = 0.012) but did not affect distant recurrences or overall survival.There were no local recurrences after EBRT for stage IE and IVE orbital low-grade NHL. The treatments offered over the study period varied, but only EBRT for stage IVE disease improved RFS. This supports EBRT as the preferred primary treatment for patients with localised orbital low-grade lymphoma, including those with bilateral disease.

Odronextamab is a hinge-stabilised, fully human IgG4-based CD20 × CD3 bispecific antibody that binds CD3 on T cells and CD20 on B cells. We aimed to evaluate the safety and antitumour activity of odronextamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.This single-arm, multicentre, phase 1, dose-escalation and dose-expansion (ELM-1) trial was conducted at ten academic sites across the USA and Germany. Patients aged 18 years or older with CD20-positive relapsed or refractory B-cell malignancies who previously received CD20-directed antibody therapy and who had at least one measurable lesion, and an ECOG performance status of 0 or 1 were included. Patients received intravenous odronextamab, according to a step-up dosing schedule in cycle 1, followed by treatment once per week at target doses ranging from 0·1 mg to 320 mg during cycles 2-4 (each cycle was 21 days). After cycle 4, maintenance treatment occurred every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint of safety was assessed by the incidence of adverse events and dose-limiting toxicities to determine the maximum tolerated dose or phase 2 dose of odronextamab, or both. Preliminary antitumour activity, as measured by objective response rate, was a secondary endpoint. This study is registered with ClinicalTrials.gov, NCT02290951.From Feb 4, 2015, to Sept 25, 2021, 145 heavily pretreated patients (median of 3 (IQR 2-5] previous therapies) were enrolled (94 to the dose-escalation and 51 to the dose-expansion part of the study). The median age of patients was 67·0 years (IQR 57·0-73·0); 101 (70%) were male and 44 (30%) were female; most participants were White (119 [82%]) and not Hispanic or Latino (132 [91%]). 42 (29%) patients received previous CAR T therapy and 119 (82%) were refractory to the last line of therapy. Median duration of follow-up was 4·2 months (IQR 1·5-11·5). During dose escalation, odronextamab was administered up to the maximum dose of 320 mg once per week and no dose-limiting toxicities were observed. The recommended dose for expansion in patients with follicular lymphoma grade 1-3a was 80 mg and was 160 mg for patients with diffuse large B-cell lymphoma. Cytokine release syndrome and neurological treatment-emergent adverse events were predominantly low grade and did not result in treatment discontinuation. The most common grade 3 or worse treatment-emergent adverse events were anaemia (36 [25%]), lymphopenia (28 [19%]), hypophosphataemia (27 [19%]), neutropenia (27 [19%]), and thrombocytopenia (20 [14%]). Serious treatment-emergent adverse events occurred in 89 (61%) of 145 patients; the most frequent were cytokine release syndrome (41 [28%]), pyrexia (11 [8%]), pneumonia (nine [6%]), and infusion-related reaction (six [4%]). Four deaths were considered related to treatment (gastric perforation in a patient with gastric involvement by lymphoma, lung infection, pneumonia, and tumour-lysis syndrome). Objective response rate was 51% (95% CI 42-59; 72 of 142). In patients with follicular lymphoma who received odronextamab doses of 5 mg or higher, the objective response rate was 91% (95% CI 75-98; 29 of 32) and the complete response rate was 72% (95% CI 53-86; 23 of 32). In patients with diffuse large B-cell lymphoma without previous CAR T-cell therapy who received doses of 80 mg or higher, the objective response rate was 53% (eight of 15) and all responses were complete responses. In patients with diffuse large B-cell lymphoma who had previous CAR T-cell therapy and received doses of 80 mg or higher, the objective response rate was 33% (ten of 30) and complete response rate was 27% (eight of 30).Odronextamab monotherapy showed a manageable safety profile and encouraging preliminary activity, including durable responses in heavily pretreated patients with B-cell non-Hodgkin lymphoma, supporting further clinical investigation in phase 2 and 3 trials.Regeneron Pharmaceuticals.

International audience; Background/Aims: Primary gastrointestinal follicular lymphomas (PGFL) are very rare. Our aim was to analyze the clinical features, management, and long-term outcomes in a prospective series of patients diagnosed with PGFL. Methods: All adult patients with PGFL, consecutively enrolled into the multicenter French study between 1990 and 2017, were evaluated and followed up prospectively after undergoing a complete work-up. Clinical, pathological and endoscopic features, as well as treatment outcomes, were analyzed. Results: Thirty-one patients (16 men, median age 62 years, range 33 to 79 years) with PGFL were included. The median follow-up was 92 months (range, 6 to 218 months). In the majority of patients (n=14), lymphoma was incidentally diagnosed during endoscopy. Otherwise, the most frequent circumstances of diagnosis were abdominal pain (n=7) and dyspepsia (n=5). The duodenum was the most common site of involvement (n=19) and multifocal localizations were seen in seven patients (22%). The most frequent first line strategy was surveillance applied in 22 patients (71%), of whom nine reached spontaneous, complete remission and 11 had stable disease. Seven patients (23%) received chemotherapy as first line treatment, and two underwent resection. Of seven patients who received chemotherapy, four achieved complete remission. In three patients, transformation into a high-grade lymphoma occurred. Conclusions: The diagnosis of PGFL is frequently fortuitous. The most common localization is in the duodenum. The disease has an indolent course and a good prognosis, however, rare cases of transformation into aggressive high-grade lymphoma may occur. An appropriate characterization and follow-up of these lymphomas is mandatory for their optimal management. (Gut Liver 2022;16:207-215

Non-Hodgkin lymphoma (NHL) is a common B/NK/T cell lymphoma. We collected detailed data about the incidence and mortality of NHL from Global Burden of Disease (GBD) Study in 2017 and extensively assessed the disease burden of NHL at the global level and also analysed its current trends according to sex, age, socio-demographic index (SDI), country and region.By obtaining relevant data from Global Burden of Disease Study in 2017, estimated annual percentage changes (EAPCs) of age-standardized rate (ASR) were calculated to assess the current trends of the rate of incidence and mortality.Globally, ASR of incidence in NHL was increased while ASR of mortality and its annual percentage change was relatively stable. EAPCs in the incidence of NHL decreased in the low SDI regions but increased in the high SDI regions. The ratio of male to female mortalities was the highest in the 50-69-year-old age group, especially in the middle and middle-high SDI regions.The incidence of NHL was increased globally, whereas the deaths and its annual percentage change were relatively stable from 1990 to 2017.Key messagesAge-standardized rate (ASR) of incidence in NHL was increased globally from 1990 to 2017.ASR of mortality and its annual percentage change in NHL were relatively stable globally from 1990 to 2017.Estimated annual percentage changes (EAPCs) in the incidence of NHL decreased in the low socio-demographic index (SDI) regions but increased in the high SDI regions.

Primary central nervous system non-Hodgkin lymphomas (PCNS-NHLs) are extranodal B-cell lymphomas with poor prognosis. The role of high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as first-line therapy is still not clear. We retrospectively collected long-term follow up data of 61 consecutive patients with PCNS-NHL at the University Hospital Düsseldorf from January 2004 to December 2016. Thirty-six patients were treated with conventional chemoimmunotherapy (cCIT) only (CT-group). Seventeen patients received an induction cCIT followed by HDT and ASCT. In the CT-group, the overall response rate (ORR) was 61% (CR 47%, PR 14%), and there were 8% treatment-related deaths (TRD). Progression-free survival (PFS) was 31.8 months, and overall survival (OS) was 57.3 months. In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%. After a median follow up of 71 months, 10 patients (59%) were still alive in CR/PR following HDT and ASCT, one patient was treated for progressive disease (PD), and 7 had died (41%, 6 PD, 1 TRD). All patients achieving CR prior to HDT achieved durable CR. In the CT-group, 8 patients (22%) were alive in CR/PR after a median follow-up of 100 months. Twenty-eight patients died (78%, 24 PD, 2 TRD, 2 deaths in remission). In the univariate analysis, the HDT-group patients had significantly better PFS (not reached vs 31.8 months, p = 0.004) and OS (not reached vs 57.3 months, p = 0.021). The multivariate analysis showed HDT was not predictive for survival. Treatment with HDT + ASCT is feasible and offers the chance for long-term survival with low treatment-related mortality in younger patients. In this analysis, ORR, PFS and OS were better with HDT than with conventional cCIT alone. This result was not confirmed in the multivariate analysis, and further studies need to be done to examine the role of HDT in PCNSL.

Most patients with advanced-stage indolent non-Hodgkin lymphoma have multiple relapses. We assessed axicabtagene ciloleucel autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory indolent non-Hodgkin lymphoma.ZUMA-5 is a single-arm, multicentre, phase 2 trial being conducted at 15 medical cancer centres in the USA and two medical cancer centres in France. Patients were eligible if they were aged 18 years or older, with histologically confirmed indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractory disease, previously had two or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients underwent leukapheresis and received conditioning chemotherapy (cyclophosphamide at 500 mg/mBetween June 20, 2017, and July 16, 2020, 153 patients were enrolled and underwent leukapheresis, and axicabtagene ciloleucel was successfully manufactured for all enrolled patients. As of data cutoff (Sept 14, 2020), 148 patients had received an infusion of axicabtagene ciloleucel (124 [84%] who had follicular lymphoma and 24 [16%] who had marginal zone lymphoma). The median follow-up for the primary analysis was 17·5 months (IQR 14·1-22·6). Among patients who were eligible for the primary analysis (n=104, of whom 84 had follicular lymphoma and 20 had marginal zone lymphoma), 96 (92%; 95% CI 85-97) had an overall response and 77 (74%) had a complete response. The most common grade 3 or worse adverse events were cytopenias (104 [70%] of 148 patients) and infections (26 [18%]). Grade 3 or worse cytokine release syndrome occurred in ten (7%) patients and grade 3 or 4 neurological events occurred in 28 (19%) patients. Serious adverse events (any grade) occurred in 74 (50%) patients. Deaths due to adverse events occurred in four (3%) patients, one of which was deemed to be treatment-related (multisystem organ failure).Axicabtagene ciloleucel showed high rates of durable responses and had a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.Kite, a Gilead Company.

Non-Hodgkin lymphoma (NHL) increased continuously since the last century in developed countries. While they are considered as disease in elder ages, a remarkable increasing incidence is also observed in German children and juveniles. The higher rates are interpreted by the changes in classification because diseases such as chronic lymphocytic leukaemia were also identified as NHL. Considerable rates of NHL were found in nuclear workers and liquidators of Chernobyl, i.e. in cases of low-dose chronical exposures. In Germany, we noticed three workers who developed NHL after decontamination of nuclear facilities. The bone marrow is generally considered as target organ for ionizing radiation, but NHL is obviously induced in the whole pool of lymphocytes. Therefore, the dosimetry in cases of typical occupational external and internal exposure must be revised. A high radiation sensitivity for NHL is a possible suspect and likely reason which may partly explain the continuous rise of the diseases in populations underlying the current increases of medical diagnostic exposure. NHL is also induced in children and juveniles with a history of diagnostic X-rays.

Several studies have suggested that estrogens have a protective function against lymphomagenesis. The treatment of breast cancer is driven by subtype classification, and the assessment of hormone receptor status is important for treatment selection. Thus, we evaluated the association between breast cancer and the incidence of NHL. We conducted a retrospective cohort study using a population-based nationwide registry in South Korea. We selected all women with newly diagnosed breast cancer between January 1st, 2002 and December 31st, 2016 who received curative treatment (N = 84,969) and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). Incident breast cancer (time-varying exposure) was the exposure and development of any type of NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mature T/NK-cell lymphomas, anaplastic large cell lymphoma (ALCL), and unspecified types of NHL, was the outcome. During follow-up, 1564 incident cases of NHL occurred. The fully adjusted Hazard Ratio (HR) for NHL associated with the development of breast cancer was 1.64 (95% CI = 1.34–2.00) after adjusting for body mass index, alcohol intake, physical activity, smoking, income, and comorbidity. The adjusted HR for NHL was much higher in participants who were aged

L-type neutral amino acid transporter 1 (LAT1) is a heterodimeric membrane transport protein involved in neutral amino acid transport. LAT1 is highly expressed in various malignant solid tumors and plays an essential role in cell proliferation. However, its role in malignant lymphoma remains unknown. Here, we evaluated LAT1 expression level in tissues from 138 patients with Non-Hodgkin lymphoma (NHL). Overexpression of LAT1 was confirmed in all types of NHL and we found that there is a significant correlation between the level of LAT1 expression and lymphoma grade. The LAT1 expression was higher in aggressive types of lymphomas when compared with static types of lymphomas, suggesting that active tumor proliferation requires nutrient uptake via LAT1. The expression level of LAT1 was inversely correlated with patients’ survival span. Furthermore, pharmacological inhibition of LAT1 by a specific inhibitor JPH203 inhibits lymphoma cell growth. In conclusion, our study demonstrated that LAT1 expression can be used as a prognostic marker for patients with NHL and targeting LAT1 by JPH203 can be a novel therapeutic modality for NHL.

IntroductionRelapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton’s tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R/R DLBCL patients.MethodsWe retrospectively reviewed R/R DLBCL patients who were administered with zanubrutinib plus salvage chemotherapy in our center between January, 2019 and December, 2021. Targeted panel sequencing of 11 lymphoma-related genes was performed on 8 patients with poor responses to zanubrutinib-based chemotherapy.Results27 R/R DLBCL patients were enrolled. Median age at this study was 59 years (range, 15-72). The best overall response rate (ORR) was 74.1% and complete remission rate was 33.3%. With a median follow-up of 11 months (range, 1-17), the median progression-free survival (PFS) was 8.1 months, and the overall survival (OS) was not achieved. The most common grade-3/4 adverse events were neutropenia (70.4%), thrombocytopenia (66.7%), and febrile neutropenia (33.3%). In multivariate analysis, early treatment and overall response after chemotherapy were independent favorable prognostic factors for PFS. Overall response after chemotherapy was an independent favorable factor for OS. Among the 8 patients with poor response to zanubrutinib-based treatment, the majority of patients had NOTCH2 mutations (n=8, 100%) and TP53 mutations (n=7, 87.5%). However, these patients achieved an ORR of 75% at 3 months after CD19-CAR-T cell therapy (including 4 cases of complete remission and 2 cases of partial remission). With a median follow-up of 9 months from CAR-T cell infusion (range, 1-16 months), the median PFS was 14.5 months, and the median OS was not reached. ConclusionWith high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.

A 54-year-old male patient, who presented with multiple lymphadenopathies, bilateral leg edema, and oscheohydrocele, was diagnosed with diffuse large B-cell lymphoma (DLBCL) stage IVB. His lymphadenopathies disappeared after six courses of R-CHOP therapy, which consist of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone); however, right hypopyon and partly remaining testicular soft tissue masses with fluorodeoxyglucose accumulation were observed. Lymphoma cell infiltration was observed in the aqueous humor of the right anterior chamber and testis, which indicates DLBCL progression. Hypopyon disappeared after the first course of intrathecal chemotherapy combined with R-HDMA therapy, which consists of rituximab and high-dose methotrexate/cytarabine, but recurred in the third course. The patient then underwent busulfan and thiotepa (BuTT) therapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) after four courses of R-HDMA therapy. Hypopyon promptly disappeared after BuTT therapy and no hypopyon recurrence was observed 9 months after auto-PBSCT. Therefore, BuTT therapy is effective for hypopyon associated with refractory DLBCL.

Background The incorporation of genetic variables into risk scores for predicting venous thromboembolic events (VTE) could improve their capacity to identify those patients for whom thromboprophylaxis would be most beneficial. Proof‐of‐concept of this is provided by the TiC‐ONCO score for predicting the risk of VTE in patients with solid tumours. Our aim was to develop a similarly improved tool—the TiC‐LYMPHO score—for predicting VTE in patients with lymphoma. Methods In a retrospective observational study of 208 patients with lymphoma, 31 (14.9%) were found to have experienced an episode of VTE either at the time of diagnosis or over the next 6 months. Clinical variables associated with VTE, determined via logistic regression analysis, plus the same genetic variables included in the TiC‐ONCO score, were used to build the TiC‐LYMPHO score algorithm. The sensitivity, specificity, predictive values and AUC of the TiC‐LYMPHO, the Khorana and ThroLy scores were compared in the same population. Results The TiC‐LYMPHO score showed a significantly higher AUC, sensitivity and NPV (0.783, 95.35% and 97.98% respectively) than the other scores. The ThroLy score showed a significantly higher specificity (96.43% vs. 54.49%; p, This is a single‐centre observational study that analyses the utility of combining genetic and clinical variables in a thromboembolism risk score in patients with lymphoma. The TiC‐LYMPHO score showed a significantly higher AUC, sensitivity and NPV (0.783%, 95.35% and 97.98%, respectively) than the other scores. These results show that by incorporating genetic and clinical data into VTE risk assessment, the TiC‐LYMPHO score can categorize patients with lymphoma better in terms of their risk of VTE and allow individualized thromboprophylaxis to be prescribed.

Background Solid organ transplant recipients have an elevated risk of cancer. Quantifying the life-years lost (LYL) due to cancer provides a complementary view of the burden of cancer distinct from other metrics and may identify subgroups of transplant recipients who are most affected. Methods Linked transplant and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987-2014). Data on LYL due to cancer within 10 years posttransplant were derived using mean survival estimates from Cox models. Results Among 221,962 transplant recipients, 13,074 (5.9%) developed cancer within 10 years of transplantation. During this period, the mean LYL due to cancer were 0.16 years per transplant recipient and 2.7 years per cancer case. Cancer was responsible for a loss of 1.9% of the total life-years expected in the absence of cancer in this population. Lung recipients had the highest proportion of total LYL due to cancer (0.45%) followed by heart recipients (0.29%). LYL due to cancer increased with age, from 0.5% among those aged birth to 34 years at transplant to 3.2% among those aged 50 years and older. Among recipients overall, lung cancer was the largest contributor, accounting for 24% of all LYL due to cancer, and non-Hodgkin lymphoma had the next highest contribution (15%). Conclusions Transplant recipients have a shortened lifespan after developing cancer. Lung cancer and non-Hodgkin lymphoma contribute strongly to LYL due to cancer within the first 10 years after transplant, highlighting opportunities to reduce cancer mortality through prevention and screening.

Objective Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of Non-Hodgkin Lymphoma (NHL). The aim of this study was to assess the clinico pathological characteristics of DLBCL specifically, among the affected individuals residing in Northern areas of Pakistan who had not been previously included in major lymphoma studies due to their remote location. Results Mean age of the patients was 49.7 years. Male: female ratio was 1.5:1. Primary site was lymph node in 99 (71.74%) patients, out of which, 36 (26.09%) patients had B symptoms and 19 (13.77%) patients had stage IV disease. 39 (28.26%) patients had primary extra nodal involvement, 4 (2.90%) patients had B symptoms and 3 (2.17%) had stage IV disease. Extra nodal sites involved in primary extra nodal DLBCL were gastrointestinal tract (GIT) 19 (48.72%), tonsils 6 (15.38%), spine 4 (10.26%), soft tissue swelling 3 (7.69%), parotid gland 2 (5.13%), thyroid 2 (5.13%) central nervous system (CNS) 1 (2.56), breast 1 (2.56%) and bone marrow 1 (2.56%). Our study revealed increased percentage of patients with nodal DLBCL in stage IV and with B symptoms. Few patients with primary extra nodal DLBCL had B symptoms and stage IV disease at presentation. GIT was the most common site of involvement in primary extra nodal DLBCL.

Observational studies with long-term follow-up of patients with primary central nervous system lymphoma (PCNSL) are scarce. Patient data over a period of four decades were retrospectively analysed from databases at Not-tingham University Hospitals Trust, UK. The cohort was delineated by two distinct therapeutic eras; the first from 01/01/1982 to 31/12/2010 (n = 147) and the second 01/01/2011 to 31/07/2020 (n = 125). The median age at diagnosis was significantly older in the second era compared to the first (69 and 65 years respectively, P = 0·003). The 3-, 6-and 12-month overall survival (OS) rates in the second era were significantly higher compared to the first, at 85%, 77%, 62% versus 56%, 49%, 38% respectively (log-rank test P < 0·0001). On multivariate analysis, high-dose methotrexate (HD-MTX)-based induction protocols employed in the second era were associated with improved OS compared to those used in the first [hazard ratio (HR) 0·40, 95% confidence interval (CI) 0·28–0·57]. Within the second era, superior OS rates were seen with the use of intensive HD-MTX protocols (including consolidation with high-dose chemotherapy and autologous stem cell transplantation) compared to non-intensive HD-MTX schedules (HR 0·47, 95% CI 0·22–0·99). Initiating chemotherapy within 14 days of biopsy and use of rituximab were independently associated with improved OS and progression-free survival during the second era. These data suggest that prompt treatment initiation and use of intensive HD-MTX-and rituximab-based protocols have resulted in improved survival outcomes for patients.

Chimeric antigen receptor (CAR) T-cells have emerged as an efficacious modality in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Clonal hematopoiesis of indeterminate potential (CHIP), a state in which mutations in hematopoietic cells give rise to a clonal population of cells, is more common in patients exposed to cytotoxic therapies, has been shown to influence inflammatory immune programs, and is associated with an adverse prognosis in patients with NHL and MM receiving autologous transplantation. We therefore hypothesized that CHIP could influence clinical outcomes in patients receiving CAR T-cell therapy. In a cohort of 154 patients with NHL or MM receiving CAR T-cells, we found that CHIP was present in 48% of patients and associated with increased rates of complete response and cytokine release syndrome severity, but only in patients younger than age 60 years. Despite these differences, CHIP was not associated with a difference in progression-free or overall survival, regardless of age. Our data suggest that CHIP can influence CAR T-cell biology and clinical outcomes, but, in contrast to autologous transplantation, CHIP was not associated with worse survival and should not be a reason to exclude individuals from receiving this potentially life-prolonging treatment.

Background Patients with prostate cancer (PC) are at a high risk of developing secondary hematologic malignancies (SHMs) after radiation therapy (RT), while no study has assessed the relationship of different treatment modalities with the occurrence of SHMs after PC at early stage. This study aimed to investigate the risks of developing SHMs in patients with T1/T2 PC undergoing different treatment modalities. Methods Patients with T1/T2 PC were identified from the Surveillance, Epidemiology, and End Results database. Competing risk regression (CRR) model was performed to evaluate the hazard ratios (HRs) of developing SHMs. As SHMs scarcely occur, the relative risk (RR) analysis was employed to compare the risks of different treatment modalities associating with the development of SHMs. Results The CRR analysis showed that undergoing RT was associated with a higher risk of developing SHMs (external beam radiation therapy [EBRT]: HR = 1.21, 95% confidence interval [CI]: 1.10–1.34; radioactive implant [RI]: HR = 1.20, 95% CI: 1.06–1.36). As for different types of SHMs, EBRT, and RI were correlated with decreased risks of developing CLL (RR = 0.67, 0.72; 95% CI: 0.53–0.85, 0.54–0.96, respectively), but with the increased risks of developing NHL (RR = 1.18, 1.23; 95% CI: 1.02–1.35, 1.05–1.44, respectively); EBRT also showed increased risks of developing acute/ chronic myeloid leukemia (AML/CML, RR = 1.54, 1.56; 95% CI: 1.16–2.03,1.05–2.33, respectively); No increased risk of developing SHMs was detected in patients who only underwent prostatectomy. Conclusions Although RT was found to be associated with the increased risks of developing SHMs in patients with T1/T2 PC, this finding cannot be extended to diverse types of SHMs. RT was correlated with the increased risks of the development of NHL, AML, and CML, but with the decreased risk of developing CLL. Prostatectomy did not increase the risk of developing SHMs., Our study used a large population‐based analysis to estimate the risk of different radiation therapy modalities for second hematologic malignancies developing after T1/2 prostate cancer. External beam radiation therapy and radioactive implant were correlated with increased risks of acute/chronic myeloid leukemia but decreased risk of chronic lymphocytic leukemia. The impact of radiation therapy on second hematologic malignancies developing after T1/2 prostate cancer was different in various types of hematologic malignancies.

BACKGROUND: Non-Hodgkin’s lymphoma (NHL) is the most common hematological malignancy in the world. Many etiologic factors have been implicated in the risk of developing NHL, including genetic susceptibility and obesity. Single-nucleotide polymorphisms (SNPs) in Ghrelin (GHRL), an anti-inflammatory hormone, and tumor necrosis factor α (TNF-α), an inflammatory cytokine, have been independently associated with the risk for obesity and NHL. OBJECTIVE: To investigate the association between SNPs in GHRL and TNF-α and the risk for NHL and obesity in Kuwaitis. METHODS: We recruited 154 Kuwaiti NHL patients and 217 controls. Genotyping was performed for rs1629816 (GHRL promoter region), rs35684 (GHRL 3’ untranslated region), and rs1800629 (TNF-α promoter region). Logistic regression analysis was performed to assess the association of the investigated SNPs with NHL and the relationship between the selected SNPs with BMI in each group separately. RESULTS: We show that rs1629816 GG was associated with an increased risk for NHL in our sample (p= 0.0003, OR 1.82; CI: 1.31–2.54). None of the investigated SNPs were associated with obesity, nor was obesity found to be associated with the risk for NHL. CONCLUSIONS: Our study demonstrates an association between rs1629816, a SNP in the GHRL regulatory region, and NHL in Kuwaitis.

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

The purpose of this study was to evaluate the clinical, endoscopic, and radiological characteristics, complications, survival outcomes, and prognostic factors of patients with primary gastrointestinal lymphoma.This study retrospectively analyzed the demographic, laboratory, endoscopic, and radiological characteristics and treatment outcomes of 43 patients with newly diagnosed primary gastrointestinal lymphoma.The median age was 62 years (range: 26-83). The primary lesion location was the gastric in 33 (77%) patients and the intestinal in 10 (23%) patients. The most common lesions were the corpus (33%) and corpus+antrum (24%) in primary gastric lymphoma and the ileum (60%) in primary intestinal lymphoma. The most common endoscopic findings were diffuse infiltrative lesion (23%) and massforming (33%), while the most common computed tomography finding was wall thickening (53%). Wall thickening and mass-forming at computed tomography were greater in primary intestinal lymphoma than in primary gastric lymphoma (P = .034). Complications were observed in 9 (21%) patients and 13 (31%) patients who underwent surgery. Complication and surgery rates were higher in primary intestinal lymphoma than in primary gastric lymphoma (P = .003 and P = .014, respectively). Five-year overall survival and 5-year eventfree survival rates were 75% and 72%, respectively. Univariate analysis showed that intestinal involvement, advanced clinical stage, a high International Prognostic Index score, mass-forming and wall thickening at computed tomography, extranodal involvement, and complication were found to adversely affect survival. Multivariate analysis revealed that intestinal involvement and a high International Prognostic Index score were independent prognostic factors for overall survival and event-free survival.Patients with primary gastrointestinal lymphoma with intestinal involvement and high International Prognostic Index score should be followed closely.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of extra-nodal non-Hodgkin’s lymphoma. Corticosteroids cause transient regression of PCNSL at the radiological and histological level. A growing number of case reports describe histologically confirmed neuroinflammation (sentinel lesions) heralding the development of PCNSL. We present two further cases of sentinel lesions contextualised by a review of past literature. Our aims are to collate existing knowledge on sentinel lesions in PCNSL and explore their pathophysiological significance. Two cases were identified (n = 2) from a cohort of 104 patients with PCNSL referred to a tertiary neurosurgery centre. A literature search identified previously reported cases (n = 14). Median age was 57.5 (range; 26–72); pre-biopsy corticosteroid administration was reported in 50% of cases (n = 8); mean time between biopsies was 10 months (range; 3–60). Common MRI features were homogenous enhancement (10;71.4%) and T2-hyperintensity (11;100%). Histochemical analysis of sentinel lesion biopsy revealed inflammatory CD3/4/5/8-positive T-cells (14; 100%), demyelination (13; 81.3%), rare/scattered CD20-postive B-cells (11;78.6%) and CD68-positive macrophages (10;71.4%). Repeat biopsy confirmed PCNSL in all cases. Waxing and waning CNS inflammation has been identified in 16 patients ultimately diagnosed with PCNSL. Neuro-specialists should be aware of this atypical presentation and maintain a high index of suspicion for lymphoma despite histopathology negative for lymphoma when clinical or radiological features indicate PCNSL.

Background Anecdotal cases of the so-called “wrap-around” appearance in non-Hodgkin lymphoma (NHL) of the spine exist in the medical literature. In this paper, we looked at the prevalence of this imaging feature in our institutional cases. Materials and Methods We screened our institutional database for biopsy-proven NHL. Our inclusion criteria were the histologically confirmed diagnosis of NHL involving any vertebra, available magnetic resonance imaging of the affected site, and a positive wrap-around sign. Exclusion criteria included lymphoma cases without the wrap-around sign and/or histology other than NHL. We subdivided the cases into 3 groups: 1) lymphoma wrapped around the vertebral body; 2) the posterior elements alone; or 3) both the vertebral body and posterior elements. Results Our search identified 147 cases of NHL in which a confirmatory biopsy at the primary tumor site was available. Of those, 23 cases fulfilled the inclusion criteria (16 men and 7 women with average age at diagnosis of 63.3 years), yielding prevalence of 15.6% in our series. Most commonly the lymphoma involved the vertebral body with or without some involvement of the posterior vertebral elements (n = 20, 86.9%), followed by posterior vertebral elements (n = 2, 8.7%). One remaining case (4.4%) had lymphoma involving the anterior vertebral body and posterior elements. Conclusions Findings of our pilot study indicated that the wrap-around sign in cases of NHL could be helpful diagnostically. This sign may be frequently under-recognized, leading to potential for a diagnostic dilemma on imaging. Larger studies are necessary to obtain more precise information about the prevalence of the wrap-around sign.

Background Calvarial lymphoma is an exceedingly rare phenomenon; the clinical presentation and imaging pattern mimic many diseases of the central nervous system. Several treatment approaches have been undertaken with variable use of surgery plus adjuvant chemotherapy and radiation; an optimal treatment algorithm has yet to be defined. The aim of this study was to better characterize management strategies and patient outcomes. Methods An illustrative case was presented and a meta-analysis was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MEDLINE and Embase were searched for cases of calvarial lymphoma. Outcomes between patients who underwent open surgery and biopsy only were compared directly. Results In an analysis from 1976 to 2019, 62 patients with a median age of 60 were included. The most common presentations were subcutaneous scalp mass (89%), headaches (26%), and focal neurological deficits (21%). Osteolytic changes on computed tomography were seen in 69% of patients with extension into either the intracranial or extracranial space in 97% of cases. Surgical excision was performed in 41 patients with a remission rate of 85% and a recurrence rate of 5%, which did not vary significantly from patients treated nonsurgically (remission in 75%, P = 0.479; recurrence in 0%, P = 1.000) Conclusions In patients presenting with a progressively enlarging scalp mass, calvarial lymphoma should be in the differential diagnosis, as it can be effectively managed with a biopsy followed by chemotherapy and radiation. The role for open surgery may be limited.

BACKGROUND Patients with mycosis fungoides (MF) are at increased risk of developing non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung cancer, bladder cancer and melanoma. The characteristics of patients developing these malignancies have not been specifically delineated. In addition, there are no established guidelines for screening MF patients for second malignancies. MATERIALS/METHODS We identified 742 patients with MF who developed second malignancies in the Surveillance Epidemiology and End Result-18 database. RESULTS The majority of second malignancy patients were white and male, mean age 55-67 years at diagnosis of MF, and mean age 61-72 years at diagnosis of second malignancy. The majority of patients diagnosed with second malignancies had early stage MF. MF patients with NHL, lung cancer, and bladder cancer tended to be diagnosed at earlier stages of the second malignancy than patients without MF and demonstrated better 5-year overall survival. There was no improvement in stage at diagnosis or survival for MF patients who were diagnosed with melanoma compared to patients without MF. CONCLUSIONS Improvements in survival in MF/NHL, MF/lung cancer and MF/bladder cancer patients may reflect differences in disease biology secondary to having MF or the importance of increased contact with the healthcare system. MF/melanoma data suggest that patients require regular pigmented-lesion-focused skin examinations. Tools for screening include regular lymph node examinations, pigmented-lesion-focused examinations and detailed review of systems questions. Smoking cessation counseling is key intervention in this population, as is ensuring that all age- and sex-specific cancer screenings are up-to-date (e.g. lung cancer screening, mammography, and colonoscopy). The utility of regular imaging for second malignancy screening and lab testing such as routine urinalysis requires additional study and expert consensus.

OBJECTIVES The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients. METHODS This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016. RESULTS The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n = 731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59 years in 2006-2008 to 62 years in 2015-2016 (P

Non-Hodgkin lymphomas (NHL) are underestimated causes of cancer in West Africa where chronic viral hepatitis and HIV are endemic. While the association with HIV infection has already been characterized, limited information is available on the association between chronic viral hepatitis and NHL in sub-Saharan Africa. A case-control study was conducted in referral hospitals of Abidjan (Cote d’Ivoire) and Dakar (Senegal). Cases of NHL were matched with controls on age, gender and participating site. The diagnosis of NHL relied on local pathological examination completed with immunohistochemistry. HIV, HBV and HCV serology tests were systematically performed. A conditional logistic regression model estimated the associations by the Odds Ratio (OR) with their 95% confidence interval (CI). A total of 117 NHL cases (Abidjan n = 97, Dakar n = 20) and their 234 matched controls were enrolled. Cases were predominantly men (68.4%) and had a median age of 50 years (IQR 37-57). While Diffuse Large B-cell lymphoma were the most reported morphological type (n = 35) among mature B-cell NHL, the proportion mature T-cell NHL (30%) was high. The prevalence figures of HBV, HCV and HIV infection were 12.8%, 7.7% and 14.5%, respectively among cases of NHL. In multivariate analysis, HBV, HCV and HIV were independently associated with NHL with OR of 2.23 (CI 1.05-4.75), 4.82 (CI 1.52-15.29) and 3.32 (CI 1.54-7.16), respectively. Chronic viral hepatitis B and C were significantly associated with NHL in West Africa. Timely preventive measures against HBV infection and access to curative anti-HCV treatment might prevent a significant number of NHL.

International audience; Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.

There is a paucity of data regarding racial disparities in the survival of patients with indolent non-Hodgkin lymphomas (iNHL) in the contemporary time-period. Hence, we sought to determine whether racial disparities exist in the survival of patients with iNHLs in the US. We included 68,059 adult patients with follicular lymphoma (FL, n=41,943), marginal zone lymphoma (MZL, n=22,485), and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM, n=3,631) who were diagnosed in the US between 2000-2017. Race was categorized as White, Black, Asian/Pacific Islander, or American Indian/Alaska Native (API/AI). The primary outcome was relative survival (RS), which was estimated using flexible parametric survival models. RS estimates varied according to race and disease histology but were consistently lower for racial minorities, including those diagnosed during the most recent 5-year time-period of 2012-2017. On multivariable analysis for RS, Black patients with FL had a 32% higher excess mortality rate compared to White patients [adjusted excess hazard ratio (aEHR), 1.32; 95% CI, 1.15-1.51; P

Primary vitreoretinal lymphoma is a great masquerader and provides a diagnostic challenge.It is most frequently misdiagnosed as a chronic uveitis. Steroid treatment for presumed uveitis can interfere with the correct diagnosis of vitreoretinal lymphoma. Herein, we present a case of primary vitreoretinal lymphoma in which the correct diagnosis was delayed by short-term steroids until 2 years later.A 45-year-old woman presented with floaters and blurred vision in her right eye for 3 months. An ocular examination revealed dense vitreous cells. Three months later, she developed headache and suicidal ideation after taking a 3-week medication of oral steroid medication from another eye clinic. Brain magnetic resonance imaging revealed a tumor involving the corpus callosum and periventricular region.Vitreous biopsy and repeated brain biopsies were carried out for the patient.A brain biopsy was performed for the first time, and a vitreous biopsy was performed when steroid medication was suspended for 20 and 41 days, respectively. Both biopsies were negative for the presence of malignant cells. Follow-up magnetic resonance imaging revealed complete remission of the brain tumor. Two years later, the tumor recurred in the optic chiasm. Diffuse large B-cell lymphoma was confirmed by a second brain biopsy.The patient had complete tumor remission after receiving brain radiation therapy and chemotherapy.Vitreoretinal lymphoma is difficult to diagnose owing to its rarity, masquerading presentation, and steroid-induced apoptosis of lymphoma cells. Physicians should consider vitreoretinal lymphoma as an important differential diagnosis in patients presenting with chronic uveitis and use steroids cautiously before making a definitive diagnosis.

The link between gastric mucosa-associated lymphoid tissue lymphoma (LG-MALT) and chronic Helicobacter Pylori (HP) infection had led to a real revolution in the management of the disease.To study the results of the HP eradication therapy and to clarify its place in the tumor response.A descriptive retrospective bicentric study, between January 2007 and December 2016, including patients with LG-MALT treated in the gastroenterology departments of Sahloul hospital in Sousse and Habib Bougtafa hospital in Bizerte, and having received treatment for eradication of HP.Sixty-three patients were included. The male/female sex ratio was 1.42. The average age was 58 years. The symptomatology was dominated by epigastric pain (96.8%). On digestive endoscopy, the most frequent location and appearance were gastric antrum (39.6%) and ulcerations (89%). The lymphoma was classified as stage IE and IIE1 in 81% and 19% of cases, respectively. The HP status was positive in all patients. The HP eradication rate was 82.5% after three anti-HP treatment courses. Complete remission of lymphoma was obtained in 81% of patients at 18 months. Non-response to HP eradication therapy was observed in 19% of patients. Non-responder patients had a longer diagnostic delay (p=0.02), more diffuse endoscopic involvement (p=0.001) and a more frequent appearance of large gastric folds (p=0.001).The course of LG-MALT is determined by the treatment for the eradication of HP. Its success promotes remission of lymphoma.

18F-Fluorodeoxyglucose (FDG) PET-CT is an excellent imaging modality for the evaluation of non-Hodgkin lymphoma (NHL). We report a case of a 45-year-old woman presented with a large right breast mass and suspicious right axillary lymph nodes referred for 18F-FDG PET-CT for staging. 18F-FDG PET-CT images show large hypermetabolic right breast mass infiltrating the skin, multiple hypermetabolic right axillary and subpectoral lymph nodes, along with multiple hypermetabolic bone lesions at axial and appendicular skeleton. Findings are mimicking primary breast cancer with nodal and bone metastases. Biopsy revealed diffuse large B cell lymphoma. 18F-FDG PETCT is helpful in evaluation of disease extent and response evaluation of primary breast lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common type of NHL, accounting for about 40% of NHL cases, and is one of the most aggressive lymphomas. DLBCL is widespread in individuals aged more than 50 years old, with a maximum incidence in the seventh decade, but it may also occur in younger patients. DLBCL may occur in any immune system tissue, including those around the gastrointestinal tract, and even in the stomach, though gastric DLBCL has yet to be sufficiently investigated. This study aimed to understand changes in gastric Diffuse Large B cell lymphoma (gastric DLBCL) development with age. Immunoglobulin (Ig) heavy chain variable region genes were amplified from sections of nine preserved biopsies, from patients whose age varied between 25 and 89 years, sequenced and analyzed. We show first that identification of the malignant clone based on the biopsies is much less certain than was previously assumed; and second that, contrary to expectations, the repertoire of gastric B cell clones is more diverse among the elderly DLBCL patients than among the young.

Non-Hodgkin lymphoma (NHL) is a common haematological cancer that is comprised of approximately 30 subtypes, of which Waldenström Macroglobulinemia (WM) is a rare incurable form. It is typically managed using a watch-and-wait strategy that can contribute to illness uncertainty which may result in fear of cancer recurrence (FCR) and poor health-related quality of life (QOL). However, few studies have examined the correlates of FCR and QOL in NHL patients, including WM patients. One-hundred males and 92 females with a mean age of 62.7 years who were an average of 6.8 years from diagnosis completed the online questionnaire which asked about demographics, medical history, QOL, FCR, stress, anxiety and depression. Few NHL patients reported significant stress or affective distress, most had moderate-high QOL and 41% experienced recent FCR, relative to published cut-off scores. Poorer QOL was related to depression symptoms, FCR, higher illness burden (i.e. comorbidity) and fewer personal resources (i.e. unemployed), whereas FCR was related to shorter time since diagnosis and more depressive symptoms. Results suggest that FCR and depressive symptoms may adversely impact QOL, whereas a recent cancer diagnosis and depression-related pessimism may contribute to FCR.

Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.

The purpose of this retrospective study was to investigate the role in staging and prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma without high-grade transformation (HT). We retrospectively reviewed 115 consecutive patients with histopathologically confirmed gastric MALT lymphoma without HT who underwent pretherapeutic F-18 FDG PET/CT. Kaplan–Meier and Cox proportional-hazards regression analyses were used to identify independent prognostic factors for disease free survival (DFS) among 13 clinical parameters and three PET parameters. In two of 115 patients (1.7%), the clinical stage appeared higher according to F-18 FDG PET/CT. In univariate analysis, Helicobacter pylori (HP) infection (P = 0.023), treatment modality (P

Introduction Superior vena cava (SVC) syndrome (SVCS) is a life-threatening occurrence that necessitates prompt treatment. At present, endovascular stenting is proposed as a first-line treatment to relieve symptoms. We assessed the effectiveness, safety and outcome of SVC stent positioning in patients affected with advanced cancer. Methods Forty-two patients undergoing stent positioning in the SVC for neoplasms from January 2002 to December 2018 form the basis of this retrospective study. Demographic data, risk factors, associated diseases, symptoms at presentation according to the score proposed by Kishi and the type of SVCS according to Sanford and Doty were collected. Minor and major complications were recorded. Suspected stent occlusion was confirmed by means of recurrence of symptoms followed by a confirmatory computed tomography (CT). Results Thirty-four (81%) patients had a nonresectable lung tumour invading or compressing the SVC. Five (12%) patients had a non-Hodgkin's lymphoma, and three (7%) had metastatic lymphadenopathies. Nitinol stents (Memotherm®) were employed in 19 (45%) patients, and steel stents (Wallstent™) in the remaining 23 (55%) patients. Thirty-five (85%) patients died during follow up for disease progression and the overall survival rate at 24 months was 11% (standard error (SE)=0.058). Thirteen patients (32%) had a recurrence of SVCS because of stent thrombosis in three (23%) and extrinsic compression from uncontrolled cancer progression in ten (77%). The overall symptom-free interval at 24 months was 57% (SE=0.095). Conclusions We recommend the use of the endovascular procedure as a first-line treatment in locally advanced or metastatic tumour in the presence of SVCS.

Characterize the population PK and exposure–response (ER) relationships of selinexor in patients with diffuse large B-cell lymphoma (DLBCL) (efficacy endpoints) or other non-Hodgkin’s lymphoma (NHL) patients (safety endpoints) to determine the optimal dose in patients with DLBCL. This work included patients from seven clinical studies, with 800 patients for PK, 175 patients for efficacy and 322 patients for safety analyses. Logistic regression models and Cox-regression models were used for binary and time-to-event endpoints, respectively. Model-based simulations were performed to justify dose based on balance between efficacy and safety outcome. Selinexor pharmacokinetics were well-described by a two-compartment model with body weight as a significant covariate on clearance and central volume of distribution and gender on clearance. Overall response rate (ORR) in patients with DLBCL increased with day 1 Cmax and decreased in patients with higher baseline tumor size (p

Objectives To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R-mini-CYVE) in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Methods We included pretreated adult patients with B-cell NHL who were ineligible for high-dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty. Up to 8 cycles were administered. Results Between 2013 and 2019, 56 patients with diffuse large B-cell lymphoma (n = 45, 80%) and indolent B-cell lymphoma (n = 11, 20%) were included. Median age was 75 (range: 36-88). Nineteen patients (35%) had a performance status ≥2. Patients received a median of 4 cycles of R-mini-CYVE. The objective response and the complete response rates were 50% and 33%, respectively. Median progression-free survival and overall survival times were 5.7 (95% CI: 0.5-10.9) and 14.7 (95% CI: 3.5-25.9) months, respectively. Grade ≥3 anaemia, thrombocytopenia and neutropenia occurred in 44%, 55% and 60% of the patients, respectively. The most frequent non-haematological grade ≥3 adverse events were sepsis (21%), fatigue (13%) and cytarabine-related neurotoxicity (5%). Conclusion R-mini-CYVE demonstrated a meaningful antitumour efficacy and an acceptable safety profile in patients with relapsed/refractory B-cell NHL who were ineligible for HDT.

As the aging society advances, the number of non-Hodgkin lymphoma (NHL) patients is increasing. Aged relapsed or refractory (r/r) NHL patients have limited treatment options. Therefore, a safe and effective regimen is urgently needed for these patients. Thus, we originally developed the MTX-HOPE (methotrexate, hydrocortisone, vincristine, sobuzoxane, and etoposide) regimen for r/r NHL and validated the safety and efficacy of this regimen in a clinical setting. We analyzed the data of 42 r/r NHL patients who received MTX-HOPE in this single-center retrospective cohort study. The median age of the patients was 81 years. The overall response rate was 45.3%. The median overall survival (OS) was 7 months, the one-year OS was 43.7%, and the two-year OS was 40.8%. Grade ≥3 neutropenia and renal dysfunction were observed in 47.6% and 11.9% of patients, respectively, and treatment-related death were not observed. Appropriate supportive care enabled these patients to continue the MTX-HOPE regimen. The proportion of patients who needed hospitalization during MTX-HOPE therapy was only 21.4%. Multivariable analyses with the Cox proportional hazards model revealed that both OS and progression-free survival (PFS) were significantly influenced by high Ki-67 expression in pathology, with response to the MTX-HOPE regimen after three to five cycles as a time-dependent covariate. Our results suggest that MTX-HOPE therapy can be an option for non-aggressive r/r NHL patients. To validate MTX-HOPE therapy, further prospective investigation is needed.

Femoral marrow magnetic resonance imaging (MRI) is a non-invasive, non-irradiated and useful modality for evaluating bone marrow (BM) conditions. Human adult femoral BM is almost uniformly fatty marrow and has the largest volume of a single bone. MRI has an extremely high resolution for fat and water, which allows high-contrast imaging of cellular infiltration into fat tissue. In hematological diseases, femoral BM MRI can clearly detect cell infiltration, which is symmetrically imaged from the proximal to the distal direction of abnormal signal areas. Thus, we investigated the significance of femoral MRI for non-Hodgkin lymphoma (NHL). We analyzed the data of 69 NHL patients who received femoral MRI at diagnosis in this single-center retrospective cohort study. The median patient age was 73 years. MRI patterns were mainly classified as uniform patterns or nonuniform patterns. We also classified the range of cellular marrow as high-grade or low-grade based on whether it had spread to over half of the femur. Both overall survival (OS) and progression-free survival (PFS) were significantly influenced by abnormal femoral marrow MRI. In particular, the patients with cellular femoral marrow lesions had a worse OS and PFS based on log-rank tests. Multivariable analyses with the Cox proportional hazards model revealed that OS and PFS were significantly influenced by cellular marrow diagnosed by femoral MRI. We concluded that femoral marrow MRI is a useful tool for detecting BM involvement and an independent prognostic factor in NHL patients.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is still a consolidation treatment choice for relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) patients and some aggressive B-cell NHL as frontline therapy. Due to the shortage of carmustine, we switched to idarubicin-substituted BEAC (IEAC) conditioning regimen. We retrospectively compared the outcomes of 72 aggressive B-cell NHL patients treated with IEAC or BEAC regimens followed by ASCT as upfront consolidative treatment. The median time to neutrophil and platelet reconstitution showed no difference between IEAC and BEAC groups. IEAC regimen was well tolerated without increase of adverse events. Transplant-related mortality didn’t occur. The overall survival (OS) and progression-free survival (PFS) of IEAC group (33 and 23 months) were a little longer than that of BEAC group (30 and 18 months). However, due to the small sample numbers, there’s no significant difference in OS and PFS between IEAC and BEAC group with DLBCL or MCL. Multivariate analysis showed that AnnArbor staging, IPI score, lactate dehydrogenase level, remission of disease, modified regimen were related with PFS and OS. In conclusion, IEAC regimen was well tolerated and replacement with idarubicin could be an alternative when carmustine was not available.

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.

The implantation of a subgaleal reservoir (ICV port) in order to apply intracerebroventricular (ICV) chemotherapy in patients with leptomeningeal cancer may be complicated by misplacement of the device, pericatheter leucencephalopathy, hemorrhage and iatrogenic ventriculitis/meningitis. Here we analyzed the occurrence of such complications in patients with primary central nervous system lymphoma (PCNSL) treated with systemic and ICV methotrexate (MTX)- and cytarabine (AraC)-based chemotherapy. We retrospectively reviewed the medical records of 94 consecutive patients (1247 installations), who had received an ICV port for intraventricular chemotherapy for treatment of histologically confirmed PCNSL at our institution between September 2005 and October 2018. Infectious and non-infectious complications were systematically recorded including clinical, laboratory and imaging data. In nine/94 patients (9.6%) a misplacement of the ICV port seen on the postoperative computed tomography (CT) scan was corrected immediately and chemotherapy was then continued as planned. In five/94 patients (5.3%) symptomatic non-infectious complications were observed (four patients with symptomatic pericatheter leucencephalopathy, one patient with surgical scar dehiscence with CSF leak). In eight/94 patients (8.5%) asymptomatic white matter lesions around the catheter were visible on cerebral magnetic resonance imaging (MRI) after completion of therapy. The rate of infectious complications was six/94 patients (6.4%). No complication was lethal or required intensive care monitoring. This retrospective study shows that complications of ICV treatment have to be expected in a fraction of patients, however, in this series these complications were manageable and did not result in long-term deficits. This article is protected by copyright. All rights reserved.