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Abstract Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p 40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

Abstract Pharmacotherapy options for chronic lymphocytic leukaemia (CLL) have expanded significantly in recent years. These options include chemotherapy, chemoimmunotherapy and signalling pathway inhibitors. A notable shift in the treatment landscape began with the widespread adoption of ibrutinib in 2016. This analysis of claims data focuses on understanding how the use of novel therapies has evolved in clinical practice over the past decade in Germany. Anonymized claims data (2010–2022) from German statutory health insurance was used, covering patient demographics, treatments, and prescriptions. The study population included patients with two confirmed CLL diagnoses. Treatment patterns were analysed, and survival outcomes were compared using time‐to‐event analyses. In the analysed cohort of 2983 incident CLL patients, 1041 started first‐line therapy between 2011 and 2022, with a median duration of 18 months from diagnosis to the first prescription. Chemoimmunotherapy, the predominant 1L therapy until 2019, decreased significantly, while targeted therapy usage increased from 3% in 2015 to 77% in 2022. Targeted therapies became dominant in patients receiving treatment for relapsed or refractory disease after 2016. Median treatment durations were: 122 days for chemo, 176 days for chemo‐immuno, and 373 days for targeted therapy. The overall survival for patients diagnosed in or after 2016 was significantly better (hazard ratio 0.56, 95% confidence interval, 0.44–0.69)). The adoption of targeted therapies like ibrutinib and venetoclax has transformed CLL treatment in Germany, leading to improved patient outcomes. Additionally, we demonstrate successful adherence to evolving clinical guidelines.

BackgroundImpact of B-cell depletion following treatment with Bruton tyrosine kinase-inhibitors (BTKi) on the outcome of SARS-CoV-2 infection in chronic lymphocytic leukemia (CLL) patients remain controversial. We investigated the impact of BTKi on susceptibility and the severity of COVID-19 in Chinese patients with CLL during the first wave of COVID-19 (Omicron variant).MethodsCLL patients (n=171) visiting the Institute of Hematology, Peoples’ Hospital, China (November 15, 2022- January 20, 2023) were included in the study. Seventeen patients receiving BTKi and venetoclax with or without obinutuzumab were excluded. Data from 117 patients receiving treatment with BTKi were collected using a standardized questionnaire through telephone interviews. Thirty-four patients without CLL-specific treatment served as controls. The data was analysed using IBM SPSS Software version 21 and a P value of

Abstract Background Little is known about the relationship between oral health status and depressive symptoms in adults in England. The aim of this study was to examine the longitudinal association between oral health parameters and depressive symptoms in adults in England. Methods Data were obtained from the English Longitudinal Study of Aging (ELSA), which included information on self-rated oral health, oral impairment in daily life (Oral Impacts on Daily Performances, OIDP), and depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D) in 6790 adults aged ≥ 50 years. Wave 3 data were used as baseline, while Waves 5 and 7 were used for follow-up assessments. Logistic regression was used to determine whether depressive symptoms at baseline anticipated self-rated oral health and OIDP and whether oral health status (at baseline) was associated with the development of depressive symptoms at follow-up assessment. Results Participants with poor self-rated oral health were at higher risk of developing depressive symptoms, even after adjusting for behavioral, clinical, and sociodemographic characteristics (OR = 1.69, 95% CI 1.38–2.07). Similarly, having oral impacts on daily performances were associated with the development of depressive symptoms: The OR for developing depressive symptoms at Wave 5 or 7 was 2.19 (95% CI 1.62–2.96) after adjustment for all covariates. Participants with depressive symptoms at baseline were more likely to report poor self-rated oral health (OR = 1.93, 95% CI 1.52–2.44) or one or more oral impacts (OR = 1.86, 95% CI 1.45–2.40) at follow-up than those without depressive symptoms at baseline, even after adjusting for confounders. Conclusions In the present study, a bidirectional association was found between depressive symptoms and poor oral health in older adults. Maintaining good oral health in older adults may be a protective factor against depressive symptoms. Therefore, more attention should be paid to promoting oral health awareness in older adults, including encouraging regular dental checkups, proper toothbrushing and flossing techniques, and healthy lifestyles.

Abstract Objectives: The goal of the present study was to evaluate the association between depression and ultra-processed food (UPF) consumption as risk factors for developing type 2 diabetes (T2D). Design: A prospective community study. Setting: Baseline data (2009–2010) from CARTaGENE community health study from Quebec, Canada, were used. Food and drink consumption was assessed using the Canadian-Diet History Questionnaire II and grouped according to their degree of processing by the NOVA classification, and participants were categorised into tertiles of UPF (g/d). Depression was defined using either a validated cut-off score on the Patient Health Questionnaire-9 or antidepressant use. The outcome was the incidence of T2D, examined in 3880 participants by linking survey data with administrative health insurance data. Cox regression models estimated the associations between UPF, depression and incident T2D. Participants: 40–69-year-old individuals at baseline. Results: In total, 263 (6·8 %) individuals developed T2D. Participants with high depressive symptoms and high UPF consumption showed the highest risk for T2D (adjusted hazard ratios (aHR) = 1·58, 95 % CI (0·98, 2·68)), compared to those with low depressive symptoms and low UPF consumption. The risk for T2D was similar when high depressive symptoms and antidepressant use were combined with high UPF (aHR 1·62, 95 % CI (1·02, 2·57)). Conclusions: This study shows that co-occurring depression and high UPF consumption were associated with a higher risk for T2D. Early management and monitoring of both risk factors might be essential for diabetes prevention.

Abstract CD19‐directed chimeric antigen receptor (CAR)‐T cell therapy has become a standard treatment for relapsed/refractory diffuse large B‐cell lymphoma (r/r DLBCL). While the benefits of CAR‐T cell treatment are clear in the general patient population, there remains a relative scarcity of real‐world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR‐T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR‐T infusion (

IntroductionThis study aimed to assess the association between depression, ultra-processed food consumption (UPFs), and the risk of developing diabetes-specific complications in adults with type 2 diabetes (T2D).MethodsBaseline data came from the CARTaGENE study, a health survey of adults (40–69 years) in Quebec, Canada. The incidence of T2D complications was examined in N= 683 participants with T2D without complications at baseline by linking survey data with administrative health data. Food and drink consumption was assessed using the Canadian Diet History Questionnaire and categorized by NOVA classification. Participants were categorized into tertiles of UPFs consumption. Depression was defined as having elevated depressive symptoms based on the Patient Health Questionnaire-9 or the use of antidepressant medications. Cox regression models were used to estimate the associations between UPFs, depression, and T2D complications.ResultsIn total, 105 individuals developed diabetes-related complications over a 7-year period. Participants with high depressive symptoms and high UPFs consumption had the highest risk for diabetes complications (adjusted hazard ratio (aHR) 2.07, 95% CI: 0.91 – 4.70), compared to participants with low depressive symptoms and low UPFs consumption. Higher risks for diabetes complications were observed when high depressive symptoms and antidepressant use were combined with high UPFs consumption (aHR 2.59, 95% CI: 1.32 – 5.06).ConclusionThis study indicates that those with co-occurring depression and high UPFs consumption have a greater risk of diabetes complications. Early management and monitoring of both risk factors might be essential to prevent diabetes complications.

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18–60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation. Response was assessed according to the standardized response criteria published in 1999, not including F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET). Primary endpoint was event-free survival (EFS). A total of 695 of 700 patients were eligible for the intention-to-treat analysis. Totally 467 patients qualified for radiotherapy of whom 305 patients were randomized to receive radiotherapy (R-CHOP-21: 155; R-CHOP-14: 150) and 162 to observation (R-CHOP-21: 81, R-CHOP-14: 81). Two hundred twenty-eight patients not qualifying for radiotherapy were randomized for R-CHOP-14 versus R-CHOP-21. After a median observation of 66 months 3-year EFS was superior in the radiotherapy-arm versus observation-arm (84% versus 68%; P = 0.0012), due to a lower rate of partial responses (PR) (2% versus 11%). PR often triggered additional treatment, mostly radiotherapy. No significant difference was observed in progression-free survival (PFS) (89% versus 81%; P = 0.22) and overall survival (OS) (93% versus 93%; P = 0.51). Comparing R-CHOP-14 and R-CHOP-21 EFS, PFS and OS were not different. Patients randomized to radiotherapy had a superior EFS, largely due to a lower PR rate requiring less additional treatment (NCT00278408, EUDRACT 2005-005218-19).

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans. Primary end point was event-free survival (EFS). A subgroup of 131 patients with PMBCLs was included (median age, 34 y; 54% female, 79% elevated lactate dehydrogenase (LDH), 20% LDH >2× upper limit of normal [ULN], and 24% extralymphatic involvement). Eighty-two (R-CHOP-21: 43 and R-CHOP-14: 39) patients were assigned to radiotherapy and 49 (R-CHOP-21: 27, R-CHOP-14: 22) to observation. The 3-year EFS was superior in radiotherapy arm (94% [95% confidence interval (CI), 89-99] versus 78% [95% CI, 66-89]; P = 0.0069), due to a lower rate of partial responses (PRs) (2% versus 10%). PR triggered additional treatment, mostly radiotherapy (n = 5; PR: 4; complete response/unconfirmed complete response: 1). No significant differences were observed in progression-free survival (PFS) (95% [95% CI, 90-100] versus 90% [95% CI, 81-98]; P = 0.25) nor in overall survival (OS) (98% [95% CI, 94-100] versus 96% [95% CI, 90-100]; P = 0.64). Comparing R-CHOP-14 and R-CHOP-21, EFS, PFS, and OS were not different. A prognostic marker for adverse outcome was elevated LDH >2× ULN (EFS: P = 0.016; PFS: P = 0.0049; OS: P = 0.0014). With the limitation of a pre-PET-era trial, the results suggest a benefit of radiotherapy only for patients responding to R-CHOP with PR. PMBCL treated with R-CHOP have a favorable prognosis with a 3-year OS of 97%.

Abstract Background Individuals with mental health problems have many insufficiently met support needs. Across sociocultural contexts, various parties (e.g., governments, families, persons with mental health problems) assume responsibility for meeting these needs. However, key stakeholders' opinions of the relative responsibilities of these parties for meeting support needs remain largely unexplored. This is a critical knowledge gap, as these perceptions may influence policy and caregiving decisions. Methods Patients with first-episode psychosis (n = 250), their family members (n = 228), and clinicians (n = 50) at two early intervention services in Chennai, India and Montreal, Canada were asked how much responsibility they thought the government versus persons with mental health problems; the government versus families; and families versus persons with mental health problems should bear for meeting seven support needs of persons with mental health problems (e.g., housing; help covering costs of substance use treatment; etc.). Two-way analyses of variance were conducted to examine differences in ratings of responsibility between sites (Chennai, Montreal); raters (patients, families, clinicians); and support needs. Results Across sites and raters, governments were held most responsible for meeting each support need and all needs together. Montreal raters assigned more responsibility to the government than did Chennai raters. Compared to those in Montreal, Chennai raters assigned more responsibility to families versus persons with mental health problems, except for the costs of substance use treatment. Family raters across sites assigned more responsibility to governments than did patient raters, and more responsibility to families versus persons with mental health problems than did patient and clinician raters. At both sites, governments were assigned less responsibility for addressing housing- and school/work reintegration-related needs compared to other needs. In Chennai, the government was seen as most responsible for stigma reduction and least for covering substance use services. Conclusions All stakeholders thought that governments should have substantial responsibility for meeting the needs of individuals with mental health problems, reinforcing calls for greater government investment in mental healthcare across contexts. The greater perceived responsibility of the government in Montreal and of families in Chennai may both reflect and influence differences in cultural norms and healthcare systems in India and Canada.

Abstract Background Individuals with mental health problems have multiple, often inadequately met needs. Responsibility for meeting these needs frequently falls to patients, their families/caregivers, and governments. Little is known about stakeholders' views of who should be responsible for these needs and there are no measures to assess this construct. This study’s objectives were to present the newly designed Whose Responsibility Scale (WRS), which assesses how stakeholders apportion responsibility to persons with mental health problems, their families, and the government for addressing various needs of persons with mental health problems, and to report its psychometric properties. Methods The 22-item WRS asks respondents to assign relative responsibility to the government versus persons with mental health problems, government versus families, and families versus persons with mental health problems for seven support needs. The items were modelled on a World Values Survey item comparing the government’s and people’s responsibility for ensuring that everyone is provided for. We administered English, Tamil, and French versions to 57 patients, 60 family members, and 27 clinicians at two early psychosis programs in Chennai, India, and Montreal, Canada, evaluating test–retest reliability, internal consistency, and ease of use. Internal consistency estimates were also calculated for confirmatory purposes with the larger samples from the main comparative study. Results Test–retest reliability (intra-class correlation coefficients) generally ranged from excellent to fair across stakeholders (patients, families, and clinicians), settings (Montreal and Chennai), and languages (English, French, and Tamil). In the standardization and larger confirmatory samples, internal consistency estimates (Cronbach’s alphas) ranged from acceptable to excellent. The WRS scored average on ease of comprehension and completion. Scores were spread across the 1–10 range, suggesting that the scale captured variations in views on how responsibility for meeting needs should be distributed. On select items, scores at one end of the scale were never endorsed, but these reflected expected views about specific needs (e.g., Chennai patients never endorsed patients as being substantially more responsible for housing needs than families). Conclusions The WRS is a promising measure for use across geo-cultural contexts to inform mental health policies, and to foster dialogue and accountability among stakeholders about roles and responsibilities. It can help researchers study stakeholders’ views about responsibilities, and how these shape and are shaped by sociocultural contexts and mental healthcare systems.

Abstract Objectives To understand users’ perceptions about receiving their personalized depression risk score and to gain an understanding about how to improve the efficiency of risk communication from the user perspective. Methods A qualitative study embedded in a randomized controlled trial (RCT) on evaluating the impact of providing personalized depression risk information on psychological harms and benefits. The participants (20 males and 20 females) were randomly selected from the intervention arm of the RCT after the 12-month assessment. The qualitative interviews were conducted through telephone, audio recorded and transcribed verbatim. We conducted a content analysis to describe the content and contextual meaning of data collected from participants. Results The first theme explained the motivation for receiving a risk score. Most participants chose to receive their personalised depression risk score with the goal of improving their self-awareness. The results revealed three sub-themes surrounding perceptions and implication of receiving their risk score: positive, negative, and neutral. Most participants found that receiving their score was positive because it improved their awareness of their mental health, but some participants could see that some people would have negative feelings when getting the score causing them to be more likely to get depression. The final theme focussed on improvements including: the best delivery methods, having resources and strategies, and targeting younger people. Conclusion The most significant motivation for, and benefit of receiving one’s personalized depression risk score was improved awareness of one’s mental health. A comprehensive risk communication program may improve the uptake and maximize the impact on behavior changes and risk reduction.

The incidence of aggressive B-cell lymphomas increases with age, but for elderly or frail patients not eligible for doxorubicin-containing treatment standard therapy remains to be defined. In this prospective, multicenter, phase-2 B-R-ENDA trial, we investigated the feasibility, toxicity, and efficacy of 8 cycles rituximab combined with 6 cycles bendamustine (BR) in elderly or frail aggressive B-cell lymphoma patients: 39 patients aged >80 years and 29 patients aged 61–80 years with elevated Cumulative Illness Rating Scalescore >6 were included. Progression-free survival (PFS) and overall survival (OS) at 2 years were 45% (95% confidence interval [CI], 28%-61%) and 46% (28%-63%) for the patients age >80, as well 32% (13%-51%) and 37% (17%-57%) for frail patients age 64–80, respectively. In a preplanned retrospective analysis, we found no significant differences in PFS and OS comparing the outcome of the 39 patients age >80 years with 40 patients aged 76–80 years treated with 6xR-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and 2 x rituximab in the RICOVER-60 trial (DSHNHL 1999-1, NCT00052936, EU-20243), yet we detected lower rates of infections and treatment-related deaths in the BR-treated patients. We demonstrate that older and frail patients with aggressive B-cell lymphoma who are not able to receive standard CHOP-based therapy can benefit from anthracycline-free therapy as a feasible and effective therapeutic option.

Abstract This cohort study aimed to compare the incidence of type 2 diabetes in adults with depression-related weight gain, depression-related weight loss, depression with no weight change, and no depression. The study sample included 59,315 community-dwelling adults in Ontario, Canada. Depression-related weight change in the past 12 months was measured using the Composite International Diagnostic Interview—Short Form. Participants were followed for up to 20 years using administrative health data. Cox proportional hazards models compared the incidence of type 2 diabetes in adults with depression-related weight change and in adults with no depression. Adults with depression-related weight gain had an increased risk of type 2 diabetes compared to adults no depression (HR 1.70, 95% CI 1.32–2.20), adults with depression-related weight loss (HR 1.62, 95% CI 1.09–2.42), and adults with depression with no weight change (HR 1.39, 95% CI 1.03–1.86). Adults with depression with no weight change also had an increased risk of type 2 diabetes compared to those with no depression (HR 1.23, 95% CI 1.04–1.45). Associations were stronger among women and persisted after adjusting for attained overweight and obesity. Identifying symptoms of weight change in depression may aid in identifying adults at higher risk of type 2 diabetes and in developing tailored prevention strategies.

Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of aggressive lymphoma. Depending on individual risk factors, roughly 60–65% of patients can be cured by chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, patients with primary refractory disease or relapse (R/R) after an initial response are still characterized by poor outcome. Until now, transplant-eligible R/R DLBCL patients are treated with intensive salvage regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) which, however, only cures a limited number of patients. It is most likely that in patients with early relapse after chemoimmunotherapy, chimeric antigen receptor (CAR) T-cells will replace high-dose chemotherapy and ASCT. So far, transplant-ineligible patients have mostly been treated in palliative intent. Recently, a plethora of novel agents comprising new monoclonal antibodies, antibody drug conjugates (ADC), bispecific antibodies, and CAR T-cells have emerged and have significantly improved outcome of patients with R/R DLBCL. In this review, we summarize our current knowledge on the usage of novel drugs and approaches for the treatment of patients with R/R DLBCL.

Abstract Background Self-help may reduce the risk of depression, and risk perception of depression may influence initiating self-help. It is unknown how risk perception is associated with self-help behaviours. The objectives of this study are to (1) describe the self-help strategies used by high-risk Canadians in relation to the accuracy of perceived depression risk, by sex, and (2) identify demographic and clinical factors associated with self-help behaviours. Methods Baseline data from a randomized controlled trial including 358 men and 356 women at high-risk of developing depression were used. Following methods used in cancer research, risk perception accuracy was determined by comparing the participant’s self-perceived and objective risk of developing depression and classifying as accurate, over-estimation and under-estimation based on a ± 10% threshold. The participant’s objective depression risk was assessed using sex-specific multivariable risk predictive algorithms. Frequency of using 14 self-help strategies was assessed. One-way ANOVA testing was used to detect if differences in risk perception accuracy groups existed, stratified by sex. Linear regression was used to investigate the clinical and demographic factors associated with self-help behaviours, also stratified. Results Compared to accurate-estimators, male over-estimators were less likely to “leave the house daily,” and “participate in activities they enjoy.” Male under-estimators were also less likely to “participate in activities they enjoy.” Both male ‘inaccurate’ perception groups were more likely to ‘create lists of strategies which have worked for feelings of depression in the past and use them’. There were no significant differences between self-help behaviours and risk perception accuracy in women. Regression modeling showed negative relationships between self-rated health and self-help scores, irrespective of sex. In women, self-help score was positively associated with age and educational attainment, and negatively associated with perceived risk. In men, a positive relationship with unemployment was also seen. Conclusions Sex differences exist in the factors associated with self-help. Risk perception accuracy, work status, and self-rated health is associated with self-help behaviours in high-risk men. In women, factors related to self-help included age, education, self-rated health status, and perceived risk. More research is needed to replicate findings. Trial registration Prospectively registered at ClinicalTrials.gov ( NCT02943876 ) as of 10/21/16.

Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum–antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers. Overall, 133 patients with SARS-CoV-2 were enrolled in pre- and post-vaccine eras: 84 non-vaccinated and 49 vaccinated, respectively. A mild course of COVID-19 was documented more frequently in vaccinated patients (49% vs. 29%), while the frequency of severe and critical courses occurred in approximately one-half of the non-vaccinated patients (22% vs. 42%, p = 0.023). Particularly, patients with hematologic neoplasms benefited from vaccination in this context (p = 0.031). Admissions to intermediate- and intensive-care units and the necessity of non-invasive and invasive respiratory support were reduced by 71% and 50% among vaccinated patients, respectively. The median length of admission was 11 days for non-vaccinated and 5 days for vaccinated patients (p = 0.002). COVID-19 mortality was reduced by 83% in vaccinated patients (p = 0.046). Finally, the median time from SARS-CoV-2 infection to restarting cancer therapy was 12 and 26 days among vaccinated and non-vaccinated groups, respectively (p = 0.002). Although this study does not have enough power to perform multivariate analyses to account for confounders, it provides data on COVID-19 in non-vaccinated and vaccinated cancer patients and illustrates the potential benefits of COVID-19 vaccines for these patients.

Background This study investigated potential psycho‐bio‐behavioral mediators of the association between adverse childhood experiences (ACEs) and the risk of coronary heart disease (CHD) in adulthood. Methods and Results Participants were 5610 British civil servants (mean age, 55.5; 28% women) from the Whitehall II cohort study without CHD at baseline in 1997 to 1999 (wave 5) when retrospective data on the number of ACEs were collected via questionnaire (range, 0–8). Potential mediators assessed at wave 5 included depression and anxiety symptoms, health behaviors (smoking, alcohol dependence, sleep, and physical activity), and cardiometabolic dysregulations. New diagnoses of CHD (myocardial infarction, definite angina, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty) were assessed from wave 6 (2001) to wave 11 (2012–2013). Logistic regressions examined associations between ACEs, potential mediators, and CHD during the follow‐up period. Natural indirect effects were examined using mediation analysis. A total of 566 (10.1%) participants developed CHD during the follow‐up period. ACEs were associated with an increased likelihood of CHD (odds ratio per ACE, 1.09; 95% CI, 1.00–1.19). Controlling for age and sex, mediation analyses revealed an indirect effect of depression symptoms (natural indirect effects, 1.05; 95% CI, 1.03–1.07), anxiety symptoms (natural indirect effects, 1.12; 95% CI, 1.10–1.15), and a greater number of cardiometabolic dysregulations (natural indirect effects, 1.02; 95% CI, 1.01–1.03) in the association between ACEs and incident CHD. Behavioral factors were not statistically significant mediators. Conclusions Depression symptoms, anxiety symptoms, and cardiometabolic dysregulations partially mediated the association between ACEs and CHD. Regular screening and treatment of symptoms of psychological disorders and cardiometabolic dysregulations may help mitigate the long‐term health burden of ACEs.

Abstract Background Major depressive disorder is one of the most prevalent and disabling forms of mental illness in the general population. One public health strategy that may reduce the disease burden is early identification and prevention - identifying people who are at high risk and intervening to prevent symptoms from progressing into a major depressive episode (MDE). Multivariable risk predictive algorithms (MVRP) have been developed to estimate personalized risk (probability) of an MDE. The purpose of this trial is to answer the questions: (1) Does disclosure of personalized depression risk information promote high-risk individuals to take preventive actions? (2) Will disclosure of personalized depression risk information negatively affect the mental health of those at high risk? Methods We are recruiting 350 high-risk men and 350 high-risk women across the country. Individuals are eligible, if they: (1) are 18 years or older, (2) have not had a depressive episode in the past two months, (3) are at high risk of MDE based on the MVRPs (predicted risk of 6.5% + for men and of 11.2% + for women), (4) can communicate in either English or French, and (5) agree to be contacted for follow-up interviews. The MVRPs were developed and validated using longitudinal data from over 10,000 Canadians across the country. Eligible participants are randomized into (1) the control group, and (2) the group receiving personalized depression risk information. The participants are assessed at baseline, 6 and 12 months regarding accuracy of risk perception, use of self-help strategies and changes in psychological distress and functioning. Qualitative interviews are conducted in sub-samples of the intervention groups to explore how the personalized information affects risk perception, self-help behaviors and mental health. Discussion MVRPs can be used for risk stratification and planning preventive actions. The personalized risk information produced by MVRPs may also empower users to actively engage in self-management. This trial will contribute to the knowledge base about the potential health benefits and psychological harms associated with the provision of personalized depression risk information that will inform future implementation and patient-physician communication in the clinical settings. Trial registration NCT02943876. Date of trial registration: October 21st, 2016.

Introduction Depression has consistently been associated with an increased risk of diabetes in recent meta-analyses. However, depression is a highly heterogeneous construct and people with specific symptoms of depression, such as weight gain and increased sleep, may be at a higher risk of diabetes. Objectives and Approach This work will compare incident diabetes in Ontario adults with recent depressive episodes that included symptoms of weight gain, weight loss, or no weight change and in those with no recent depressive episodes. Participants will be drawn from several waves of the Canadian Community Health Survey and the National Population Health Survey. Past 12-month depressive episodes and weight change during most recent or worst episodes was measured using the CIDI/CIDI short form. Time to incident diabetes will be ascertained through linkage with the Ontario Diabetes Database. Cox proportional hazards regression will assess diabetes incidence by depression and weight change characteristics. Results This study will include 106 084 Ontario adults who participated in the Canadian Community Health Survey (2000/2001, 2002, 2003, 2012) and the National Population Health Survey (1996). Follow-up time will range from 4 to 19 years (until March 2017). Study covariates will include demographic and lifestyle factors, comorbidities, and health care use and will be extracted from the surveys above and from administrative health data. The dataset for this study is currently being prepared by the Institute for Clinical Evaluative Sciences (ICES) and the findings of this analysis will be presented at this conference. Conclusion/Implications The results of this work will provide insight into who, among those with depression, is at highest risk of new-onset diabetes. These results will be relevant to the development of both personalized and population-level diabetes screening and prevention strategies.

Depression and diabetes are independent risk factors for one another, and both are associated with increased risk of cognitive decline. Diabetes patients with lower cognitive function are more likely to suffer poorer health outcomes. However, the role of depression in cognitive decline among people with diabetes is not well understood. This systematic review assessed whether adults with comorbid diabetes and depression or depressive symptoms exhibit greater cognitive decline relative to individuals with diabetes alone. Searches were run in CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, and PubMed (MEDLINE) with no time or language restrictions. Studies were eligible for inclusion if they were of any quantitative study design, included participants aged 18 years or older with diabetes mellitus of which some must have presented with current depression, and measured cognition as an outcome. The Cochrane Collaboration's Risk Of Bias In Non-randomized Studies-of Interventions tool was used for quality assessment of each study and its collected outcome. Fifteen articles were included in the final analysis. The high degree of heterogeneity in exposures, outcomes, and participant characteristics precluded a meta-analysis of any of the studies, and the risk of bias observed in these studies limits the strength of the evidence. Nonetheless, this review found the presence of comorbid depression was associated with poorer cognitive outcomes than for persons with diabetes alone. While large-scale preventive efforts must address epidemic levels of diabetes and its comorbidities, on the patient level healthcare professionals must be cognizant of the added difficulties that depression poses to patients and the extra support required to management diabetes in these cases. This systematic review is registered with the University of York Centre for Reviews and Dissemination under registration number 2015:CRD42015025122.

High depressive symptoms and cardiometabolic abnormalities are independently associated with an increased risk of diabetes. The purpose of this study was to assess the association of co-occurring depressive symptoms and cardiometabolic abnormalities on risk of diabetes in a representative sample of the English population aged 50 years and older. Data were from the English Longitudinal Study of Ageing. The sample comprised of 4454 participants without diabetes at baseline. High depressive symptoms were based on a score of 4 or more on the 8-item binary Centre for Epidemiologic Studies-Depression scale. Cardiometabolic abnormalities were defined as 3 or more cardiometabolic risk factors (hypertension, impaired glycemic control, systemic inflammation, low high-density lipoprotein cholesterol, high triglycerides, and central obesity). Cox proportional hazards regressions assessed the association between co-occurring depressive symptoms and cardiometabolic abnormalities with incidence of diabetes. Multiple imputation by chained equations was performed to account for missing data. Covariates included age, sex, education, income, smoking status, physical activity, alcohol consumption, and cardiovascular comorbidity. The follow-up period consisted of 106 months, during which 193 participants reported a diagnosis of diabetes. Diabetes incidence rates were compared across the following four groups: 1) no or low depressive symptoms and no cardiometabolic abnormalities (reference group, n = 2717); 2) high depressive symptoms only (n = 338); 3) cardiometabolic abnormalities only (n = 1180); and 4) high depressive symptoms and cardiometabolic abnormalities (n = 219). Compared to the reference group, the hazard ratio for diabetes was 1.29 (95% CI 0.63, 2.64) for those with high depressive symptoms only, 3.88 (95% CI 2.77, 5.44) for those with cardiometabolic abnormalities only, and 5.56 (95% CI 3.45, 8.94) for those with both high depressive symptoms and cardiometabolic abnormalities, after adjusting for socio-demographic, lifestyle and clinical variables. These findings suggest that those with high depressive symptoms and cardiometabolic abnormalities are at a particularly increased risk of type 2 diabetes.

Long-term therapies such as disease modifying therapy for Multiple Sclerosis (MS) demand high levels of medication adherence in order to reach acceptable outcomes. The objective of this study was to describe adherence to four disease modifying drugs (DMDs) among statutorily insured patients within two years following treatment initiation. These drugs were interferon beta-1a i.m. (Avonex), interferon beta-1a s.c. (Rebif), interferon beta-1b s.c. (Betaferon) and glatiramer acetate s.c. (Copaxone).This retrospective cohort study used pharmacy claims data from the data warehouse of the German Institute for Drug Use Evaluation (DAPI) from 2001 through 2009. New or renewed DMD prescriptions in the years 2002 to 2006 were identified and adherence was estimated during 730 days of follow-up by analyzing the medication possession ratio (MPR) as proxy for compliance and persistence defined as number of days from initiation of DMD therapy until discontinuation or interruption.A total of 52,516 medication profiles or therapy cycles (11,891 Avonex, 14,060 Betaferon, 12,353 Copaxone and 14,212 Rebif) from 50,057 patients were included into the analysis. Among the 4 cohorts, no clinically relevant differences were found in available covariates. The Medication Possession Ratio (MPR) measured overall compliance, which was 39.9% with a threshold MPR≥0.8. There were small differences in the proportion of therapy cycles during which a patient was compliant for the following medications: Avonex (42.8%), Betaferon (40.6%), Rebif (39.2%), and Copaxone (37%). Overall persistence was 32.3% at the end of the 24 months observation period, i.e. during only one third of all included therapy cycles patients did not discontinue or interrupt DMD therapy. There were also small differences in the proportion of therapy cycles during which a patient was persistent as follows: Avonex (34.2%), Betaferon (33.4%), Rebif (31.7%) and Copaxone (29.8%).Two years after initiating MS-modifying therapy, only 30-40% of patients were adherent to DMDs.

To investigate the effect of the neighbourhood built environment on trajectories of depression symptom episodes in adults from the general Canadian population.We used 10 years of data collection (2000/01-2010/11) from the Canadian National Population Health Study (n = 7114). Episodes of depression symptoms were identified using the Composite International Diagnostic Interview Short-Form. We assessed the presence of local parks, healthy food stores, fast food restaurants, health services and cultural services using geospatial data. We used latent class growth modelling to identify different trajectories of depression symptom episodes in the sample and tested for the effect of neighbourhood variables on the trajectories over time.We uncovered three distinct trajectories of depression symptom episodes: low prevalence (76.2% of the sample), moderate prevalence (19.2%) and high prevalence of depression symptom episodes (2.8%). The presence of any neighbourhood service (healthy food store, fast-food restaurant, health service, except for cultural service) was significantly associated with a lower probability of a depression symptom episode for those following a trajectory of low prevalence of depression symptom episodes. The presence of a local park was also a significant protective factor in trajectory groups with both low and moderate prevalence of depression symptom episodes. Neighbourhood characteristics did not significantly affect the trajectory of high prevalence of depression symptom episodes.For individuals following a trajectory of low and moderate prevalence of depression symptom episodes, the neighbourhood built environment was associated with a shift in the trajectory of depression symptom episodes. Future intervention studies are recommended to make policy recommendations.

BackgroundSelf-rated health (SRH) is a single-item measure that is one of the most widely used measures of general health in population health research. Relatively little is known about changes and the trajectories of SRH in people with chronic medical conditions. The aims of the present study were to identify and describe longitudinal trajectories of self-rated health (SRH) status in people with diabetes.MethodsA prospective community study was carried out between 2008 and 2011. SRH was assessed at baseline and yearly at follow-ups (n=1288). Analysis was carried out through trajectory modeling. The trajectory groups were subsequently compared at 4 years follow-up with respect to functioning.ResultsFour distinct trajectories of SRH were identified: 1) 72.2% of the participants were assigned to a persistently good SRH trajectory; 2) 10.1% were assigned to a persistently poor SRH trajectory; 3) mean SRH scores changed from good to poor for one group (7.3%); while 4) mean SRH scores changed from poor to medium/good for another group (10.4%). Those with a persistently poor perception of health status were at higher risk for poor functioning at 4 years follow-up than those whose SRH scores decreased from good to poor.ConclusionsSRH is an important predictor for poor functioning in diabetes, but the trajectory of SRH seems to be even more important. Health professionals should pay attention to not only SRH per se, but also changes in SRH over time.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD.284 ADHD children were stratified by weight status/BMI according to WHO classification and compared with regard to their neurocognitive characteristics, motivational style, and motor profile as assessed by a comprehensive battery of tests. All comparisons were adjusted for demographic characteristics of relevance including, socioeconomic status (SES).Both Obese and overweight ADHD children exhibited significantly lower SES compared to normal weight ADHD children. No significant differences were observed between the three groups with regards to their neurocognitive, emotional and motor profile.Our findings provide evidence that differences in weight/BMI are not accounted for by cognitive, motivational and motor profiles. Socio-economic characteristics are strongly associated with overweight and obesity in ADHD children and may inform strategies aimed at promoting healthier weight.

Background Although Hodgkin’s lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting.Design and Methods In this phase II study 92 patients with relapsed Hodgkin’s lymphoma and an HLA-identical sibling, a matched unrelated donor or a one antigen mismatched, unrelated donor were treated with salvage chemotherapy followed by reduced intensity allogeneic transplantation. Fourteen patients showed refractory disease and died from progressive lymphoma with a median overall survival after trial entry of 10 months (range, 6–17). Seventy-eight patients proceeded to allograft (unrelated donors, n=23). Fifty were allografted in complete or partial remission and 28 in stable disease. Fludarabine (150 mg/m2 iv) and melphalan (140 mg/m2 iv) were used as the conditioning regimen. Anti-thymocyte globulin was additionally used as graft-versus-host-disease prophylaxis for recipients of grafts from unrelated donors.Results The non-relapse mortality rate was 8% at 100 days and 15% at 1 year. Relapse was the major cause of failure. The progression-free survival rate was 47% at 1 year and 18% at 4 years from trial entry. For the allografted population, the progression-free survival rate was 48% at 1 year and 24% at 4 years. Chronic graft-versus-host disease was associated with a lower incidence of relapse. Patients allografted in complete remission had a significantly better outcome. The overall survival rate was 71% at 1 year and 43% at 4 years.Conclusions Allogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin’s lymphoma. The reduced intensity conditioning approach significantly reduced non-relapse mortality; the high relapse rate represents the major remaining challenge in this setting. The HDR-Allo trial was registered in the European Clinical Trials Database (EUDRACT, https://eudract.ema.europa.eu/) with number 02-0036

Background Research on prognostically relevant immunohistochemical markers in diffuse large B-cell lymphomas has mostly been performed on retrospectively collected clinical data. This is also true for immunohistochemical classifiers that are thought to reflect the cell-of-origin subclassification of gene expression studies. In order to obtain deeper insight into the heterogeneous prognosis of diffuse large B-cell lymphomas and to validate a previously published immunohistochemical classifier, we analyzed data from a large set of cases from prospective clinical trials with long-term follow-up.Design and Methods We performed morphological and extensive immunohistochemical analyses in 414 cases of diffuse large B-cell lymphoma from two prospective randomized clinical trials (NHL-B1/B2, Germany). Classification into germinal center and non-germinal center subtypes of B-cell lymphoma was based on the expression pattern of CD10, BCL6, and IRF4. Multivariate analyses were performed adjusting for the factors in the International Prognostic Index.Results Analyzing 20 different epitopes on tissue microarrays, expression of HLA-DR, presence of CD23+ follicular dendritic cell meshworks, and monotypic light chain expression emerged as International Prognostic Index-independent markers of superior overall survival. Immunoblastic morphology was found to be related to poor event-free survival. The non-germinal center subtype, according to the three-epitope classifier (CD10, BCL6, and IRF4) did not have prognostic relevance when adjusted for International Prognostic Index factors (relative risk=1.2, p=0.328 for overall survival; and relative risk=1.1, p=0.644 for event-free survival).Conclusions The previously reported International Prognostic Index-independent prognostic value of stratification into germinal center/non-germinal center B-cell lymphoma using the expression pattern of CD10, BCL6, and IRF4 was not reproducible in our series. However, other markers and the morphological subtype appear to be of prognostic value.

Background The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin’s lymphoma remains controversial.Design and Methods To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant.Results Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II–IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free.Conclusions This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkin’s lymphoma.

Background The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion.Design and Methods Three hundred and thirty-eight allogeneic transplant teams from 35 primarily European countries were asked to report numbers of fatalities, severe adverse events and hematologic malignancies occurring among their hematopoietic stem cell donors.Results Two hundred and sixty-two of the 338 teams (77.5%) responded to a first survey (1993–2002) and 169 of the 262 responder teams (65%) to a second survey (2003–2005). They had performed a total of 51,024 first allogeneic hematopoietic stem cell transplantations, of which 27,770 were bone marrow and 23,254 peripheral blood. They observed five donor fatalities, one after a bone marrow donation and four after peripheral blood donation (incidence 0.98 per 10,000 donations; 95% CI 0.32–2.29), 37 severe adverse events (7.25/10,000; 95% CI 5.11–9.99), of which 12 in bone marrow donors (4.32/10,000; 95% CI 2.24–7.75) and 25 in peripheral blood donors (10.76/10,000; 95% CI 6.97–15.85; p

Background Growth factors are frequently used to aid peripheral blood progenitor cell mobilization from bone marrow. This phase 2 study examined the efficacy and safety of pegfilgrastim for mobilizing peripheral blood progenitors cells for autologous transplantation.Design and Methods Patients with non-Hodgkin’s lymphoma received one cycle of mobilizing chemotherapy (ifosfamide, carboplatin and etoposide, ICE). Twenty-four hours later they were randomized, double-blind, to receive a single dose of pegfilgrastim 6 mg or 12 mg, or filgrastim 5 μg/kg/day (until the end of leukapheresis). Following leukapheresis (collection phase), patients rested or received one or two ‘salvage’ cycles of ICE. High-dose BEAM chemotherapy was then given before peripheral blood progenitor cell transplantation. The primary end-point was the patients’ mean yield of CD34+ cells/kg during the collection phase.Results Ninety patients were randomized and received a study drug; 63% completed the collection phase. The patients’ mean (95% CI) CD34+ cell harvest per leukapheresis was 0.8 (0.5–1.4), 0.8 (0.5–1.6) and 1.2 (0.7–2.0)×106 cells/kg for the pegfilgrastim 6 mg, pegfilgrastim 12 mg and filgrastim groups, respectively. Twenty (69%), 17 (59%) and 23 (72%) patients in these three groups achieved the targeted minimum harvest (≥2×106 cells/kg). The mean total harvests were 1.7, 1.4 and 2.2×106 cells/kg, respectively. Post-transplantation, the median days to absolute neutrophil count recovery (≥0.5×109/L) were 12, 11, and 11, respectively. Pegfilgrastim and filgrastim were generally well tolerated.Conclusions Pegfilgrastim (6 or 12 mg) was effective for mobilizing peripheral blood progenitors cells in patients with non-Hodgkin’s lymphoma. These data may aid the design of studies to clarify optimal dosing and leukapheresis with pegfilgrastim.

Allogeneic transplantation of hematopoietic stem cells (allo-SCT) is being increasingly used to treat patients with lymphoma. We describe current results of allo-SCT in patients with Hodgkin’s disease, indolent lymphoma including Waldenström’s disease, and aggressive lymphoma including mantle cell lymphoma and mature T-cell lymphomas. A Graft-vs.-Lymphoma (GvL) effect is present in most entities as evidenced by the generally lower relapse rates after allo-SCT and the results of donor lymphocyte infusions. Slowly proliferating diseases like chronic lymphocytic leukemia, indolent lymphomas, and some T-cell lymphomas are particularly sensitive to the effects of allogeneic T-cells while patients with Hodgkin’s disease and aggressive lymphoma may need vigorous debulking before allo-SCT to achieve optimal results. Although reduced-intensity conditioning has lowered transplant-related mortality in most and improved survival in some sub-entities, relapse rates in patients with Hodgkin’s disease and aggressive B-cell lymphomas, as well as in patients with heavily pre-treated and refractory lymphoma, remain high and further improvement is undoubtedly needed. Large prospective studies in well-defined entities are necessary to further clarify the role of allo-SCT in lymphoma.

Background and Objectives Autologous stem cell transplantation (ASCT) is effective in mantle cell lymphoma (MCL). We investigated whether incorporation of rituximab into the high-dose regimen might further improve the results of ASCT in patients with MCL.Design and Methods In a prospective phase II study, patients with newly diagnosed MCL were treated with a sequential dose-escalating therapy comprising standard chemotherapy for remission induction, intensive ara-C-containing chemotherapy for mobilization of stem cells, and myeloablative therapy followed by ASCT. The myeloablative regimen consisted of total body irradiation and high-dose cyclophosphamide supplemented with two doses (375 mg/m3) of rituximab. Outcome parameters (toxicity, clinical and molecular response as assessed by allele-specific IGH real-time quantitative polymerase chain reaction (RQ-PCR), event-free survival, and overall survival) were compared with those of 34 historical controls treated identically but without rituximab.Results Thirty-four patients were accrued. Whereas engraftment, toxicity and clinical response were not different from those in controls, event-free survival was significantly increased with rituximab (not reached vs. 43 months; hazard ratio 0.38; p=0.036). This was associated with a trend for a superior molecular response rate in 11 study vs. 10 control patients with a marker available (73% vs. 30%, p=0.086) despite similar levels of lymphoma contamination of the stem cell inocula infused.Interpretation and Conclusions Incorporation of two standard doses of rituximab into the myeloablative regimen might improve outcome of upfront ASCT for MCL, allowing long-term disease control to an extent previously not reached in this disease.