Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients

Background: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. Patients and methods: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. Results: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: −3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (−7.4 and −8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. Conclusion: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impac

Neurocognitive function of lymphoma patients after treatment with chemotherapy

BACKGROUND: Chemotherapy has been shown to cause brain changes and to compromise cognitive function in cancer survivors. Knowledge about this matter is of vital importance for good clinical practice and insights into neurological aging. However, most studies have been conducted among breast cancer patients. Less is known about the effects of chemotherapy on the cognitive function of lymphoma patients. MATERIAL AND METHOD: We studied patients with non-Hodgkin or Hodgkin lymphoma who had been treated with standard dose chemotherapy or with supplementary high dose chemotherapy when standard dose chemotherapy had been unsuccessful. Age- and sex-matched relatives and friends were invited to participate as control participants. All participants underwent a cognitive examination with a battery of validated neuropsychological tests. RESULTS: Matching of patients with control participants was found to be successful. Regression analysis did not reveal worse cognitive functioning of patients (N = 106) compared to matched controls (N = 53) on the overall group level (All Bonferroni-Holm corrected p-values >0.05). However, a subgroup of 16% of patients had deviant performance according to a chance-corrected criterion based on Ingraham and Aiken's probability curves, i.e. 1.5 standard deviations below the norm on three of 14 tests. Exploratory analyses showed that this subgroup of patients was lower educated and had lower estimated premorbid intelligence. CONCLUSION: Chemotherapy may compromise the function of the brain in a subgroup of lymphoma patients. We hypothesize protection of the brain by 'cognitive or brain reserve' as a possible explanation

Rituximab treatment results in impaired secondary humoral immune responsiveness

In lymphoma patients, treatment with chimeric CD20 monoclonal antibodies (rituximab) results in a depletion of normal and malignant B cells, persisting for 6 to 9 months. This B-cell depletion leads neither to a decrease in immunoglobulin levels nor an increase in the number of infectious complications. However, the effect of rituximab treatment on the immune responsiveness is unknown. In 11 patients with relapsed, low-grade lymphoma, we investigated the effect of rituximab treatment on the humoral immune response to primary antigens and 2 recall antigens. After rituximab treatment, the humoral immune response to the recall antigens was significantly decreased when compared with the response before treatment. Already before rituximab treatment, none of these patients was able to mount a response to the primary antigens. These findings are relevant regarding the feasibility of rituximab in maintenance treatment and may also offer a rationale for the treatment of antibody-mediated autoimmune diseases with rituxima

Health-related physical fitness in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation

Objectives We aimed to examine health-related physical fitness and its demographic and clinical correlates in patients recently treated with autologous stem cell transplantation. Design Cross-sectional study. Methods In 109 patients (multiple myeloma: n = 58, lymphoma: n = 51, median age: 55, range: 19–67 years) maximal exercise testing was conducted to assess cardiorespiratory fitness (VO2peak). Upper and lower extremity muscle strength were assessed with hand grip- and fixed dynamometry and body composition with whole body DXA scans. In addition, we assessed the patients’ demographic and clinical characteristics and examined whether they were associated with health-related physical fitness. Results VO2peak was 21.7 (5.5) mL/min/kg, 26% below reference values. Muscle strength was also reduced when compared with reference values (upper extremity: 90%, lower extremity: 80%) and 73% of our population was classified as overweight or obese. Being female and being older were significantly associated with a lower cardiorespiratory fitness (gender: β = −2.7, 95%CI = −4.6;−0.7 mL/min/kg; age: β = −0.2, 95%CI = −0.3;−0.1 mL/min/kg), upper (gender: β = −17.7, 95%CI = −20.1;−15.3 kg; age: β = −0.2, 95%CI = −0.3;−0.1 kg) and lower (gender: β = −58.3, 95%CI = −73.5;− 43.0 Nm; age: β = −1.7, 95%CI = −2.4;−1.1 Nm) extremity muscle strength. Patients who were non-smoking (β = −5.3, 95%CI = −8.7;−1.9), women (β = 7.2, 95%CI = 4.8;9.6) and diagnosed with multiple myeloma (β = 4.6, 95%CI = 2.2;6.9) had a higher percentage body fat. Conclusions The physical fitness deficits in this population indicate the need for targeted interventions. Trial registration Netherlands Trial Register - NTR234

Impact of hyperglycemia on the efficacy of chemotherapy-A systematic review of preclinical studies

Antineoplastic agents can provoke hyperglycemia in cancer patients with and without diabetes mellitus. We systematically reviewed the impact of hyperglycemia on the efficacy of chemotherapy. MEDLINE was searched for preclinical intervention studies which compared chemotherapy response in hyperglycemic and euglycemic conditions. Thirteen preclinical studies, including 23 cell lines and 2 animal experiments were identified. In 14 cell lines and 2 animal studies, chemotherapy response was lower in a hyperglycemic (>15mmol/L) compared to a euglycemic environment (5mmol/L). The response was similar in 4 cell lines. In the remaining 5 cell lines, the hyperglycemic environment potentiated chemotherapy efficacy. Hyperglycemia attenuated the antiproliferative effect of chemotherapy in preclinical experiments, but the results are inconsistent. Whether hyperglycemia influences efficacy of chemotherapy in patients needs to be explore

Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an EORTC cohort study

Background and Objectives. Second cancer has been associated with the treatment of non-Hodgkin's lymphoma (NHL), but few studies have addressed this issue considering specific treatments.Design and Methods. We estimated risk by standardized incidence ratios (SIR) and absolute excess risk (AER) based on general population rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years) treated for aggressive NHL in four successive EORTC (European Organization for Research on Treatment of Cancer) trials.Results. All patients received fully-dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14% high-dose treatment. Half of the patients needed salvage treatment and 37% were followed for more than 10 years. The cause of death was NHL in 79% of the patients; 4% died of second cancer with a median survival 8.9 (0.8-20.5) years. Cumulative incidences (death from any cause being a competing event) were 5% and 11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in young patients high risks were observed for leukemia (SIR 16.7, 95% Cl 1.4-93.1, AER 5.0), Hodgkin's lymphoma (SIR 60.1, 95% Cl 12.4-175.2, AER 15.7), colorectal cancer (SIR 12.5, 95% Cl 2.6-36.5, AER 14.7) and lung cancer (SIR 15.4; 95% Cl 4.2-39.4, AER 19.8), while risk in patients older than 45 years matched that in the normal population. The risk of cancer was significantly raised by smoking and salvage treatment.Interpretation and Conclusions. Half of the patients die of aggressive NHL before living long enough to experience second cancer. Only young patients have a high risk of second cancer during follow-up beyond 10 years.</p

Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an EORTC cohort study

Background and Objectives. Second cancer has been associated with the treatment of non-Hodgkin's lymphoma (NHL), but few studies have addressed this issue considering specific treatments. Design and Methods. We estimated risk by standardized incidence ratios (SIR) and absolute excess risk (AER) based on general population rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years) treated for aggressive NHL in four successive EORTC (European Organization for Research on Treatment of Cancer) trials. Results. All patients received fully-dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14% high-dose treatment. Half of the patients needed salvage treatment and 37% were followed for more than 10 years. The cause of death was NHL in 79% of the patients; 4% died of second cancer with a median survival 8.9 (0.8-20.5) years. Cumulative incidences (death from any cause being a competing event) were 5% and 11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in young patients high risks were observed for leukemia (SIR 16.7, 95% Cl 1.4-93.1, AER 5.0), Hodgkin's lymphoma (SIR 60.1, 95% Cl 12.4-175.2, AER 15.7), colorectal cancer (SIR 12.5, 95% Cl 2.6-36.5, AER 14.7) and lung cancer (SIR 15.4; 95% Cl 4.2-39.4, AER 19.8), while risk in patients older than 45 years matched that in the normal population. The risk of cancer was significantly raised by smoking and salvage treatment. Interpretation and Conclusions. Half of the patients die of aggressive NHL before living long enough to experience second cancer. Only young patients have a high risk of second cancer during follow-up beyond 10 years