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B Conclusion: b Our results show that a high level of the M2 macrophage marker sCD163 is a negative prognostic factor in MCL, both in the chemoimmunotherapy and the ibrutinib/lenalidomide eras. B Introduction: b The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed towards the tumor immune microenvironment, where macrophages play an important role. [Extracted from the article]

However, in Era M2, patients achieving EFS24 had similar OS compared to the general population (SMR = 1.35, 95% CI: 0.83-2.09), and lymphoma was no longer the leading cause of death (Figure 1 B&E). Multicohort Study of Conditional Survival and Cause of Death After Achieving Event-Free Survival at 24 Months (EFS24) in Patients With Mantle Cell Lymphoma (MCL) In Era M1, patients achieving EFS24 still had inferior OS compared to the general population (SMR = 2.81, 95% CI: 1.98-3.88), and lymphoma remained the leading cause of death. [Extracted from the article]

Background: The outcome for diffuse large B‐cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R‐CHOP. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known. Method: We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma‐free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population‐based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models. Results: Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14–1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10–2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01–1.64). Among younger patients (≤70), a short‐term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30‐day survival among patients and comparators. Conclusion: DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival. [ABSTRACT FROM AUTHOR]

Expressed on tumor B cells, CD32b triggers rituximab internalization, and tumor CD32b expression correlates inversely with response to rituximab or rituximab-containing therapy in MCL, FL, and DLBCL. However, approximately 15% of patients are refractory to treatment, and 25% relapse within 3 years following treatment. B Introduction: b Anti-CD20 antibodies, such as rituximab, are an essential therapy resource in patients with B-cell lymphomas. [Extracted from the article]

Enhanced ctDNA Profiling Reveals Molecular Determinants of Response and Resistance in Relapsed and Refractory Mantle Cell Lymphoma (NLG-MCL7-VALERIA) B Introduction: b Deciphering molecular determinants of response to targeted treatments and early detection of refractoriness in patients with relapsed and refractory (R/R) mantle cell lymphoma (MCL) could individualize treatment, improve outcomes and limit unnecessary toxicities. Notably, contrasting ctDNA clearance, the analysis of the post-therapy cell-free DNA revealed positive selection of clonal hematopoiesis drivers following therapy exposure, such as I TP53 i mutations in 77% of the patients. [Extracted from the article]

A few patients with MCL present with limited stage disease and for these, involved node radiotherapy may be a well tolerable alternative to immunochemotherapy regimens. How to choose between curative radiotherapy or chemotherapy in low stage MCL? Here, we aim to evaluate progression free survival (PFS) and overall survival (OS) in relation to given treatment and prognostic factors in patients with stage I-II MCL. [Extracted from the article]

B Introduction: b With modern treatments, mantle cell lymphoma (MCL) patients may experience long-lasting remission resulting in a growing population of long-term survivors. Higher rates in patients were observed across all primary treatment groups: Nordic-MCL2 protocol (250 patients, HR SB adj sb = 1.4(1.0-2.0)), R-CHOP single (144 patients, HR SB adj sb = 2.0(1.3-2.9)), R-bendamustine (302 patients, HR SB adj sb = 2.2(1.7-2.7)), lenalidomide (16 patients, HR SB adj sb = 4.3(2.0-9.0)) (Figure 1), R-CHOP/Cytarabine (145 patients, HR SB adj sb = 1.6(1.0-2.5)), and ibrutinib (9 patients, HR SB adj sb = 4.8(1.2-18.7)) contrasted with comparators. B Conclusions: b MCL survivors have an increased risk of SM, particularly patients given primary treatment with R-bendamustine, but also patients treated with other chemotherapies or novel targeted drugs (lenalidomide, ibrutinib), though only few patients were included in the latter group and the results should be interpreted accordingly. [Extracted from the article]

We speculate that the higher survival rate among young high-risk patients may be driven by the introduction of CAR-T in the last few years, whereas the more general and successive improvement among older patients could be due to intensified treatment schemes in the primary as well as relapsed settings. B Introduction: b Most patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are cured with primary immunochemotherapy, but about one in four experience relapsed/refractory (R/R) disease with worsened outcome. In young high-risk patients, the 2-year RS increased from 71% among patients diagnosed 2007-2009, to 83% among patients diagnosed 2019-2021 ( I p i SB overall sb < 0.001). [Extracted from the article]

Background: Comorbidity impacts overall survival amongst patients with diffuse large B-cell lymphoma (DLBCL). However, associations of comorbidity with lymphoma characteristics, treatment selection and lymphoma-specific mortality are less well known.Objective: To examine the impact of comorbidity on DLBCL characteristics, treatment intent and cause of death.Methods: We identified 3905 adult patients diagnosed with DLBCL 2007-2013 through the Swedish Lymphoma Register. We assessed comorbid disease history according to the Charlson comorbidity index (CCI). Comorbidity data and causes of death were collected through register linkage. Associations were estimated using multinomial regression and flexible parametric survival models.Results: Overall, 45% of the patients (n = 1737) had a history of at least one comorbidity at DLBCL diagnosis (cardiovascular disease, diabetes and solid cancer were most frequent), and 997 (26%) had a CCI score of ≥2. The relative probability of presenting with poor performance status (PS > 2) was higher amongst comorbid patients [Relative Risk Ratio (RRR)PS>2 : 2.02, 95% CI: 1.63-2.51]. Comorbid patients had a substantially lower relative probability of receiving curative treatment (RRR: 0.48, 95% CI: 0.38-0.61). Amongst all patients, CCI ≥ 1 was associated with a significantly increased risk of all-cause and lymphoma-specific death after adjustments. Amongst patients selected for curative treatment, comorbidity was associated with an increased risk of all-cause death (HRCCI>1 : 1.54, 95% CI: 1.32-1.80), but not with lymphoma-specific death (HRCCI>1 : 1.05, 95% CI: 0.86-1.28).Conclusion: Comorbidity is associated with inferior DLBCL outcome, mainly due to a lower likelihood of receiving treatment with curative intent. Possibly, more comorbid DLBCL patients could be treated with curative intent if comorbid conditions were optimized in parallel. [ABSTRACT FROM AUTHOR]

Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first-line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders. [ABSTRACT FROM AUTHOR]

25% had low Ig, defined as any deficiency, 18% had low IgG, 37% lymphopenia and 13% both low Ig and lymphopenia. Furthermore, hypogammaglobulinemia was associated with an increased risk of severe infections, indicating that hypogammaglobulinemia is common in DLBCL at diagnosis and may have clinical impact in terms of treatment complications and outcome. [Extracted from the article]

There are some evidences that hypogammaglobulinemia in newly diagnosed diffuse large B cell lymphoma (DLBCL) is a predictor for inferior outcome, but the risk for infection-related admissions specifically related to hypogammaglobulinemia is not known. The aim was to explore if hypogammaglobulinemia in untreated DLBCL in a Swedish cohort was associated with inferior outcome, and to assess the relationship between low immunoglobulin (Ig) levels and infections. Using data from the Swedish Lymphoma Register, we retrospectively identified patients above18 years diagnosed with DLBCL, receiving anthracycline-based curative therapy during 2000-2015 in Southern Sweden with Ig-levels tested at baseline. Data on Ig levels and infections were collected from medical records. Five hundred eighty-five patients were included, median age was 69 years. Hypogammaglobulinemia was detected at baseline in 24%, the most common Ig deficiency was IgG (18%), followed by IgA (10%) and IgM (8%). Hypogammaglobulinemia was associated with inferior overall survival (HR 1.4, 95% CI 1.0-1.8, p-value 0.018), but not when adjusted for International Prognostic Index (IPI). Low levels of Ig were associated with more infections during lymphoma treatment (p-value 0.013), also when adjusted for IPI (p-value < 0.001). Among patients with IgG deficiency, 47% had ≥ 1 infections versus 35% in patients with normal IgG (HR 1.2, p = 0.025). In conclusion, hypogammaglobulinemia was a frequent finding in patients with newly diagnosed DLBCL, with clinical impact in terms of treatment complications and outcome., (© 2024 John Wiley & Sons Ltd.)

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8 cycles of CHOP(-like) therapy and 22% received 3-4 cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4 cycles vs. 6-8 cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4 cycles versus 6-8 cycles of CHOP(-like) therapy were comparable., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real-world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007-2014. Survival and associations with disease characteristics, second-line treatment and fulfilment of chimaeric antigen receptor (CAR) T-cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (≤70 years 9.6 months, >70 years 4.9 months). Early relapse (≤12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second-line treatment and 34% received autologous stem cell transplantation (ASCT). Two-year OS among transplanted patients was 56% (early relapse ≤12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression-free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real-world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Mantle cell lymphoma (MCL) is a rare, often aggressive type of B-cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health-related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ-C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG-MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment. Fifty-one patients were enrolled, median age was 71 years (range 62-84), 37 were men (73%). Pre-treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre-treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long-term HRQOL., (© 2021 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

We characterised patients with mantle cell lymphoma (MCL) with poor prognosis based on differences in immune infiltration. Different expressions of the tumour cell markers Cyclin D1 and sex-determining region Y-box transcription factor 11 (SOX11), and the immune markers cluster of differentiation 3 (CD3), CD4, CD8, CD25, forkhead box protein P3 (FoxP3), T-box transcription factor TBX21 (T-bet), programmed cell death protein 1 (PD-1), programmed-death ligand 1 (PD-L1) and CD163 were investigated for all-cause mortality in 282 patients with MCL and time-to-progression (TTP) in 106 clinical trial patients. With increasing age, a significantly lower infiltration of CD3 + T lymphocytes was seen. T-cell infiltration was independent of cellular tumour antigen p53 (p53) expression, Ki-67, morphology and frequency of tumour cells. The all-cause mortality was higher in patients with PD-L1-expression above cut-off [hazard ratio (HR) 1·97, 95% confidence interval (CI) 1·18-3·25, adjusted for sex and MCL International Prognostic Index (MIPI)] and a higher frequency of CD163 + cells (continuously, HR 1·51, 95% CI 1·03-2·23, adjusting for age, sex, morphology, Ki-67 and p53). In patients treated within the Nordic Lymphoma Group MCL2/3 trials, TTP was shorter in patients with a higher frequency of FoxP3 + cells (HR 3·22, 95% CI 1·40-7·43) and CD163 + cells (HR 6·09, 95% CI 1·84-20·21), independent of sex and MIPI. When combined a higher frequency of CD163 + macrophages and PD-L1 + cells or high CD163 + macrophages and FoxP3 + regulatory T cells indicated worse outcome independent of established risk factors. The T-cell infiltrate was in turn independent of molecular characteristics of the malignant cells and decreased with age., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Survival for patients diagnosed with mantle cell lymphoma (MCL) has improved drastically in recent years. However, patients carrying mutations in tumour protein p53 (TP53) do not benefit from modern chemotherapy-based treatments and have poor prognosis. Thus, there is a clinical need to identify missense mutations through routine analysis to enable patient stratification. Sequencing is not widely implemented in clinical practice for MCL, and immunohistochemistry (IHC) is a feasible alternative to identify high-risk patients. The aim of the present study was to investigate the accuracy of p53 as a tool to identify patients with TP53 missense mutations and the prognostic impact of overexpression and mutations in a Swedish population-based cohort. In total, 317 cases were investigated using IHC and 255 cases were sequenced, enabling analysis of p53 and TP53 status among 137 cases divided over the two-cohort investigated. The accuracy of predicting missense mutations from protein expression was 82%, with sensitivity at 82% and specificity at 100% in paired samples. We further show the impact of p53 expression and TP53 mutations on survival (hazard ratio of 3·1 in univariate analysis for both), and the association to risk factors, such as high MCL International Prognostic Index, blastoid morphology and proliferation, in a population-based setting., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Patients with diffuse large B-cell lymphoma (DLBCL) who fail to complete planned treatment with R-CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R-CHOP for reasons unrelated to non-response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R-CHOP were identified through the Swedish lymphoma register 2007-2014. Of these, 147 (5%) stopped prematurely after 1-3 cycles of R-CHOP for reasons unrelated to non-response, 168 (5%) after 4-5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non-response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index ≥1 were significantly associated with failure to complete planned R-CHOP treatment for other reasons than non-response. Non-completion of treatment strongly correlated with survival. Five-year overall survival for patients who received 1-3 cycles was 26% (95% CI: 19%-33%), 49% (95% CI: 41%-57%) for 4-5 cycles and 76% (74%-77%) for patients who completed treatment. Failure to complete planned R-CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion., (© 2020 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.)

Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000-2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

The prognosis for mantle cell lymphoma (MCL) remains poor. Our aim was to assess the impact of comorbidities on survival and causes of death. For 1,385 MCL patients (1,009 males, 376 females) diagnosed in 2000-2014 (median age 71 years, range 22-96) comorbidities ≤ 10 years of diagnosis were classified according to the Charlson comorbidity index (CCI; 0, 1, 2+). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to compare lymphoma-specific and all-cause mortality rates. Model-based predictions were used to obtain probabilities of death. Overall, 44% had any comorbidity (CCI 1+) and 28% severe comorbidity (CCI 2+). Over a median follow-up of 3·7 years (range 0-16), 633 (46%) died, the majority (76%) from lymphoma. Severe comorbidity was independently associated with higher all-cause [hazard ratio (HR) = 1·52; 95% CI: 1·24-1·85) and lymphoma-specific mortality (HR = 1·31; 95% CI: 1·04-1·65). Particularly among patients with connective tissue, renal and psychiatric diseases, and dementia. Among females with any comorbidity, non-lymphoma deaths represented a larger proportion of all deaths, compared to males with any comorbidity. In general, more efficient lymphoma treatments need to be considered also for patients with severe comorbidity. However, among females with any comorbidity, the likelihood of non-lymphoma death was still considerable, perhaps favouring a more liberal use of a "wait and watch" approach., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Survival has improved among patients with diffuse large B-cell lymphoma (DLBCL) with the addition of anti-CD20 antibody therapy. We aimed to quantify trends and remaining loss in expectation of life (LEL) due to DLBCL at a national population-based level. Patients diagnosed with DLBCL 2000-2013 (N = 7114) were identified through the Swedish Lymphoma Registry and classified according to the age-adjusted International Prognostic Index (aaIPI). The novel measure LEL is the difference between remaining life years among patients and the general population and was predicted using flexible parametric models from diagnosis and among 2-year survivors, by age and sex. Median age at DLBCL-diagnosis was 70 (18-105) years and 54.8% presented with stage III-IV disease. On average, LEL due to DLBCL decreased from 8.0 (95% CI: 7.7-8.3) to 4.6 (95% CI: 4.5-4.6) years over the study period. By risk group, LEL was most reduced among patients with aaIPI ≥2 aged 50-60 years. However, these patients were still estimated to lose >8 years in 2013 (eg, LEL males50years 8.6 years (95% CI: 5.0-12.3)). Among 2-year survivors, LEL was reduced from 6.1 years (95% CI: 5.6-6.5) (aaIPI ≥ 2) and 3.8 years (95% CI: 3.6-4.1) (aaIPI < 2) to 1.1 (95% CI: 1.1-1.2) and 1.0 year (95% CI: 0.8-1.1), respectively. The reduction was observed across all ages. Results for females were similar. By using LEL we illustrate the improvement of DLBCL survival over time. Despite adequate immunochemotherapy, substantial LEL among patients with IPI ≥ 2 points to remaining unmet medical needs. We speculate that observed reduced losses among 2-year survivors indicate a reduction of late relapses., (© 2018 Wiley Periodicals, Inc.)

Comorbidity impacts survival in B-cell lymphoma patients, but the influence in peripheral T-cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression-free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front-line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low-intensity treatments. Among patients aged ≥75 years (n = 214), low-intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front-line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline-based chemotherapy in elderly PTCL patients might be of limited benefit., (Copyright © 2017 John Wiley & Sons, Ltd.)

Anaplastic large cell lymphomas (ALCLs) are rare CD30+ peripheral T-cell lymphomas (PTCLs) classified according to the expression of the anaplastic lymphoma kinase (ALK+) protein or not (ALK-). We have analysed the outcome and risk factors for survival in a population-based bi-national cohort of patients with systemic ALK+ ALCL. A total of 122 adult (≥18 years) patients diagnosed with ALK+ ALCL between 2000 and 2010 were identified from the Danish and Swedish lymphoma registries, representing 0·4% of all lymphomas. The median age of the cohort was 40 years (range 18-85). The 5-year overall survival and progression-free survival (PFS) was 78% and 64%, respectively. Age was strongly associated with outcome, and only bone marrow (BM) involvement was independently associated with poorer PFS in multivariate analysis (Hazard Ratio [HR] = 8·57, P < 0·001). Age stratification of the patients demonstrated an association between treatment with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone) and improved overall survival for patients aged 41-65 years, even when adjusted for risk factors (HR = 0·38, P = 0·047). Our results suggest that the addition of etoposide to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) in the treatment for ALK+ ALCL seems reasonable in this age group., (© 2017 John Wiley & Sons Ltd.)

No randomised study in the rituximab era has been performed specifically to evaluate addition of etoposide to treatment of diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the outcome with three chemotherapy regimens (R-CHOP-21, R-CHOP-14 and R-CHOEP-14) in a population-based cohort in terms of overall survival, adjusted for clinical prognostic factors. Through the Swedish Lymphoma Registry, 3443 patients with DLBCL were identified 2007-2012. Among all patients, there was no evidence of a difference between the regimens, after adjustment for prognostic factors. However, when restricted to patients aged up to 65, R-CHOEP-14 was associated with superior outcome compared to both R-CHOP-21 (hazard ratio: 0.49, 95% confidence interval: 0.3-0.9, p = 0.028) and R-CHOP-14 (hazard ratio: 0.64, 95% confidence interval: 0.4-1.0, p = 0.06), when adjusted for prognostic factors. Results were consistent in an additional stratified analysis with patients grouped according to age and IPI-score. In conclusion, we could show that R-CHOEP-14 was associated with superior overall survival in patients with DLBCL aged up to 65 years, indicating that this may be a valid treatment option for this patient population. To further investigate which patient groups that may benefit the most from treatment intensification, R-CHOEP-14 should be compared to R-CHOP-21 in a randomised setting. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Young patients with diffuse large B-cell lymphoma (DLBCL) are variably treated with rituximab combined with cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP), CHOP-etoposide (R-CHOEP), and anthracycline-based regimens with the addition of high-dose cytarabine/methotrexate (R-HDA/M). Using the nationwide, population-based Swedish Lymphoma Registry, we evaluated outcome, by treatment and Healthcare Region, in all 751 DLBCL patients aged ≤60 years without central nervous involvement, diagnosed in Sweden between 2007 and 2012. Overall survival was estimated using multivariate Cox analysis. In patients with age-adjusted international prognostic index (aaIPI) ≥ 2, the 5-year overall survival (OS) was 70%, 76% and 85% after R-CHOP, R-CHOEP and R-HDA/M, respectively (P = 0·002); the corresponding estimates were 40%, 55%, and 92% in aaIPI = 3 (P = 0·014). There were large therapeutic differences between Sweden's six Healthcare Regions for aaIPI ≥ 2: three were "Moderate" (more R-CHOP) and three "Intensive" (more R-CHOEP and R-HDA/M). Patients with aaIPI ≥ 2 who were treated in the Intensive Regions, showed better OS (P < 0·00005), particularly those with aaIPI = 3 (5-year OS, 62% vs. 30%; P < 0·00005). There were no regional differences in therapy or survival in patients with aaIPI < 2. We conclude that in younger high-risk patients, survival appears superior after more intensive therapy than R-CHOP., (© 2016 John Wiley & Sons Ltd.)

In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL., (© 2016 John Wiley & Sons Ltd.)

Central nervous system (CNS) involvement is rare in patients with Hodgkin lymphoma (HL). Thus, the clinical features and outcomes are not well described. Cases of histologically confirmed CNS HL diagnosed between 1995 and 2015 were retrospectively identified in institutional (n = 7), national (n = 2), and cooperative group (n = 1) databases. We screened 30,781 patients with HL in our combined databases and identified 21 patients meeting eligibility criteria, an estimated frequency of 0.07%. CNS involvement was present at initial diagnosis in 10 patients (48%) and a feature of relapsed/refractory disease in 11 (52%). Among these 11 patients, the median time from initial diagnosis of HL to development of CNS involvement was 1.9 years (range 0.4-6.6) and the median number of prior lines of therapy was 2 (range 1-7). Altogether, treatments included radiation, multiagent systemic chemotherapy, combined modality therapy, and subtotal resection. The overall response rate was 65%. After a median follow-up of 3.6 years (range 0.8-13.2) from diagnosis of CNS HL, the median PFS and OS were 7.6 and 29 months, respectively. CNS involvement as a feature of relapsed/refractory disease was adversely prognostic for both PFS and OS; however, four patients remain alive and free of relapse at 7-78 months follow-up. CNS involvement in HL is exceedingly rare and has a distinct clinical presentation with predilection for parenchymal lesions with dural extension. Around one-quarter of patients, mostly with CNS involvement at initial HL diagnosis, experience prolonged disease-free survival. Am. J. Hematol. 91:894-899, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)