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Diffuse large B-cell lymphoma is an aggressive disease occurring primarily in elderly patients. Despite high curative rates with doxorubicin-containing treatment, some elderly patients receive less intensive treatments, mainly due to advanced age, comorbidities, and concerns of cardiotoxicity from doxorubicin-containing regimens. We analyzed 1009 patients aged 75 years or older and 10,090 age- and sex-matched comparisons. We aimed to evaluate long-term cardiovascular side effects in elderly patients treated with doxorubicin. Approximately, 64% of patients received doxorubicin-containing treatment. These patients had a persistently increased risk of new-onset heart failure with a hazard ratio of 1.5 and 1.7 when conditioning on survival without heart failure to 6 and 24 months, respectively. Moreover, we observed an increased risk of venous thromboembolism during the first six months following the lymphoma diagnosis. On the contrary, no difference in risk of developing ischemic heart disease or stroke following doxorubicin-containing treatment was observed. [ABSTRACT FROM AUTHOR]

High-dose prednisolone is used in first-line treatment for lymphoma, but the potential adverse impact on bone health is unclear. Danish patients with diffuse large B-cell lymphoma or follicular lymphoma diagnosed between 2000 and 2012 were matched to the background population. Osteoporotic events (osteoporosis treatment or low-energy fracture) were identified using the Danish National Patient Registry and Prescription Registry. In total, 2589 patients and 12,945 controls were included. Lymphoma patients had increased risk of osteoporotic events compared to the matched population (hazard ratio 1.61 [95% confidence interval 1.40;1.84]). The 5- and 10-year cumulative risks of osteoporotic events for lymphoma patients were 10.0% [8.6;11.4] and 16.3% [13.8;18.7], whereas corresponding risks in the background population were 6.8% [6.3;7.3] and 13.5% [12.4;14.6]. Patients without osteoporotic event in the first two years after treatment were not at higher risk of osteoporotic events in subsequent years. Risk factors for osteoporotic events were female sex and age >70 years. [ABSTRACT FROM AUTHOR]

Richter's transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Approximately, 2–10% of patients with CLL develop RT, most often as diffuse large B-cell lymphoma. To assess the incidence of RT, we examined risk factors for RT and death among patients with RT in a nationwide CLL cohort (from 2008 to 2016). Among 3772 patients, 113 had biopsy-proven RT. With a median follow-up of 4.3 years, the 5-year cumulative incidence of RT was 2.8%. Advanced Binet stage (B/C) (p<.001), unmutated IGHV (p<.001), and del(17p) (p<.001) were independently associated with risk of developing RT. Half of the patients with RT (49%) were treatment-naïve prior to transformation and demonstrated longer survival after RT compared to patients previously treated for CLL (6.1 vs. 2.8 years, p=.03). Whether this finding could be explained by a higher proportion of clonally unrelated RT among treatment-naïve patients, remain to be addressed. [ABSTRACT FROM AUTHOR]

The addition of the antibody rituximab to CHOP (R-CHOP) has improved the outcome of diffuse large B-cell lymphoma (DLBCL) and is the current standard of care [[1]]. On the contrary, preliminary results from a trial randomizing stage II-IV DLBCL patients to R-CHOP14 and R-CHOP14 plus additional rituximab on day 8 during the first four treatment cycles did not confirm a benefit of intensified rituximab in male patients [[12]]. Consistent with this study, a more recent Swedish study including >7000 DLBCL patients reported comparable improvements in life expectancy for male and female patients during the rituximab introduction period, although no direct comparison between male and female patients was performed [[15]]. As the survival in the general population is gender-specific (5-year OS, 94% for a female and 90% for a male Danish person aged 65 in 2010), crude OS differences between male and female patients may be sensitive to excess deaths in male patients unrelated to DLBCL. [Extracted from the article]

We investigated if survival was predicted by nadir neutrophil counts after the first cycle of R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Neutrophil counts (109/L) were categorized in four grades in the nadir time frame. Prognostic indices and comorbidity levels were calculated and used to adjust the Cox regression model. Kaplan–Meier and Cox regression methods were used to estimate and compare survival. We identified 965 patients. Grade 4 neutropenia was present in 432 (45%). Grade 0 patients had a 5-year overall survival of 67%, grade 1–2: 78%, grade 3: 64%, and grade 4: 57%. Compared with grade 0 adjusted hazard ratios (HR) for death were: 0.77 (95% CI 0.49–1.21) for grade 1–2, 1.18 (95% CI 0.82–1.71) for grade 3, and 1.33 (95% CI 1.02–1.73) for grade 4. Grade 4 neutropenia after the 1st cycle of chemotherapy predicted inferior outcome compared with grade 0 and 1–2. Grade 1–2 neutropenia seemed to have superior outcome. [ABSTRACT FROM AUTHOR]

In Hodgkin lymphoma (HL) bleomycin can induce pulmonary toxicity (BPT). BPT consists of respiratory tract symptoms during bleomycin-exposure and radiologic pulmonary lesions without concomitant infection. Older age, bleomycin dose, smoking history and the use of granulocyte-colony stimulating factor (G-CSF) have been suggested as possible risk factors for BPT. It is still debated whether BPT affects overall (OS) and progression-free survival (PFS). We investigated the incidence of BPT along with possible risk factors in 412 HL patients treated in 1990-2014. BPT occurred in 34 patients (8%) and was significantly associated with disseminated disease and B-symptoms. It was more frequent in elderly patients (p =.05) but not significantly correlated with a history of smoking. BPT occurred more often in patients receiving G-CSF (p =.03), particularly the poly-ethylenglycol-bound molecule. All significant risk correlations were limited to the age group >45 years. In the present cohort, BPT did not influence OS or PFS regardless of age. [ABSTRACT FROM AUTHOR]

AbstractUp to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria. [ABSTRACT FROM AUTHOR]