Eva Futtrup Maksten

Summary: Infectious complications after high‐dose therapy and autologous stem cell transplantation (HDT‐ASCT) for lymphoma are the leading cause of late non‐relapse mortality. Characterizing the risk of infectious complications over time is important for rational follow‐up and because alternatives to HDT‐ASCT exist for some patients. This national cohort study investigated the risk of severe (defined by requiring hospitalization) late infections after 90 days among HDT‐ASCT‐treated patients with lymphoma in remission relative to the Danish background population (comparators) matched on age, sex and comorbidity score. Anti‐cancer treatment after HDT‐ASCT and death were competing events. This study included 781 patients and 3905 comparators. With a median follow‐up of 7.7 years for patients, the incidence rate ratios of severe infections from 90 days until 2 years after HDT‐ASCT was 8.43 (95% confidence interval (CI): 6.98–10.16) and the 2‐year cumulative risk was 23.7% (95% CI: 20.7%–26.7%) for patients and 3.4% (95% CI: 2.9%–4.0%) for comparators. The risk of severe infections remained increased for up to 10 years after HDT‐ASCT. Respiratory tract infections were the most frequent type, with a 2‐year cumulative risk difference of 10.9% (95% CI: 8.6%–13.3%). Patients were more likely to be prescribed anti‐infectives, including broad‐spectrum antibiotics 5–10 years after HDT‐ASCT.

Background/Objectives: Patients with chronic myeloid leukemia (CML) have a long life expectancy due to modern treatment. However, treatment may have adverse effects that hamper work ability. Methods: Patients aged 25–60 years diagnosed in 2002–2020 were included in this nationwide matched cohort study examining work ability from diagnosis (index date), including the need for permanent disability compensation (flexible job or disability pension). Each patient was matched 1:5 on sex, birth year, and level of comorbidity with citizens from the general Danish population without CML. The risks of requiring flexible job and disability pension were calculated by cause-specific hazard ratios (HRs) using Cox proportional hazards regression, and the Aalen–Johansen estimator was used to determine cumulative risks. Results: A total of 489 patients with CML and 2445 matched comparators were included. The median age was 46 years, and males comprised 59.5% of the cohort. Matched comparators were more likely to work at index date and 1, 3, 5, and 10 years after the index date (p < 0.001). The HRs of requiring both flexible job (HR 8.7 (95% confidence interval (CI): 6.1;12.2, p < 0.001)) and disability pension (HR 3.7 (95% CI: 2.8;4.9, p < 0.001)) were higher among patients diagnosed with CML compared to matched comparators. The cumulative risk of requiring flexible job and disability pension also increased in patients with CML compared to matched comparators (p < 0.001). Conclusions: Patients with CML have a reduced work ability compared to the general population. More research is needed to determine the cause of their loss of ability to work.

Purpose: To assess and describe chemotherapy-induced peripheral neuropathy (CIPN), a well-known complication to cancer treatment, using different methodologies in hematological patients. Methods: Patients scheduled for treatment with vincristine, bortezomib, or lenalidomide were included in this longitudinal observational study. The patients were examined for CIPN before treatment (baseline), before each chemotherapy cycle, one month after end of treatment, and one year after baseline using patient-reported outcomes (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Ntx-13 (FACT/GOG-Ntx-13)) and clinician-assessed outcomes (the Common Terminology Criteria for Adverse Events (CTCAE) and the Total Neuropathy Score-clinical version (TNSc©)). Results: A total of 23 patients with 171 examination visits were included between 2020 and 2022. Four patients were treated with vincristine, five with bortezomib, and fourteen with bortezomib and lenalidomide combined. Defining CIPN as a ≥ 10% decrease in the FACT/GOG-Ntx-13, 11 patients (47.8%) developed CIPN during treatment and follow-up. CTCAE score for paresthesia increased from baseline throughout treatment until 1 month after the last treatment (p ≤ 0.045). Overall, the highest proportion of CIPN was present at cycle 3–4 and 1 month after last treatment. Conclusion: This study describes the course of CIPN in patients treated with vincristine, bortezomib, or lenalidomide using both patient-reported and clinician-assessed outcomes. The highest proportion of CIPN was present at cycle 3–4 and 1 month after treatment, at which timepoints clinicians must be especially aware of CIPN. Trial registration: Registered at Clinicaltrials.gov (Trial Registration Number: NCT04393363) on March 19, 2020.

Purpose: This nationwide Danish cohort study compared overall survival (OS) between non-Western immigrant patients and Danish-born patients with lymphoma in Denmark. Furthermore, differences in clinical and socioeconomic variables were compared, and mediators of OS differences were explored to explain possible outcome differences. Patients and Methods: The study included a total of 540 non-Western patients and 16,294 Danish-born patients diagnosed with lymphoma in the period 2000– 2020. Inverse probability weighting and mediation analysis using a natural effects Cox model were used to investigate the causal relationship between immigration status and OS. Results: Indirect effects mediated through differences in performance status and income indicated a trend towards inferior OS for non-Western immigrant patients with HRs of 1.06 (0.99– 1.14) and 1.06 (0.99– 1.14). However, no total causal effect of immigration status on OS was observed overall (HR: 0.94 [0.79– 1.12]) and within subtype-specific analyses, except for classical Hodgkin lymphoma. Conclusion: No significant differences in OS between non-Western immigrant patients and Danish-born patients were discovered. Plain Language Summary: Non-Western immigrant lymphoma patients in Western countries may face multiple challenges, including lower socioeconomic status and insufficient language proficiency, which can make navigating the complexity of modern lymphoma treatment difficult. This study investigated whether the Danish tax-based healthcare system has overcome these challenges and delivered non-Western immigrant patients quality care on the same levels as that of the Danish-born patients. Therefore, using available population based Danish registries, survival between these groups were compared, while adjusting for important clinical differences, and no significant effect of immigration status on survival was found even though non-Western immigrant patients generally had lower socioeconomic status.

Purpose: To explore haematological cancer survivors’ experience of chemotherapy-induced peripheral neuropathy (CIPN) in everyday life. Methods: Data were generated by means of individual semi-structured interviews with 12 haematological cancer survivors who experience CIPN after completion of treatment. Data were analysed using thematic analysis. Results: The thematic analysis yielded an in-depth description of the experience of CIPN symptoms and the influence of the symptoms on everyday life as being unwell despite being cured. Four main themes emerged from the analysis: (1) A diffuse and contradictory sensation which is impossible to ignore in everyday life , (2) Not feeling well, even though I’m cured , (3) Living with CIPN, despite limitations , and (4) An invisible companion, that everybody knows about. Conclusion: The findings shows that survival from haematological cancer does not always equal well-being, as experiencing CIPN has extensive consequences on everyday life. CIPN affects haematological cancer survivors’ transition to an ordinary everyday life, with disturbances in the physical function, daily activities, social relationships, psychological aspects, and work ability. As a diffuse and contradictory symptom, CIPN appears as an invisible companion that leads to a feeling of being alone. Implications for Cancer Survivors: A better and deeper understanding of haematological cancer survivors’ experience of CIPN in everyday life may improve communication, guidance, and treatment of CIPN symptoms. The results suggest a need for interventions and strategies to accommodate the gap in practice and to address the impact of CIPN in everyday life.

Summary: Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin‐containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population‐based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age‐ and sex‐matched comparators from the background population. Median follow‐up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30–3.68]), with a 10‐year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35–26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43–2.76]), with a 10‐year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43–1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B‐symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work‐up of pulmonary symptoms.

Purpose: Most adult patients diagnosed with acute lymphoblastic leukemia (ALL) are below retirement age. The overall survival of patients with ALL has improved with implementation of high intensity pediatric-inspired treatment protocols. However, this treatment comes with a risk of long-term complications, which could affect the ability to work. The aim of this study was to investigate the risk of disability pension (DP) and return to work (RTW) for patients with ALL. Patients and Methods: Patients aged 18– 60 years diagnosed with ALL between 2005 and 2019 were identified in the Danish National Acute Leukemia Registry. Each patient was matched with five comparators from the general population on birth year, sex, and Charlson Comorbidity Index. The Aalen-Johansen estimator was used to calculate the cumulative risk of DP for patients and comparators from index date (defined as 1 year after diagnosis) with competing events (transplantation or relapse, death, retirement pension, or early retirement pension). Differences in cumulative incidences were calculated using Gray’s test. RTW was calculated as proportions one, three, and five years after the index date for patients holding a job before diagnosis. Results: A total of 154 patients with ALL and 770 matched comparators were included. The 5-year cumulative risk of DP was increased fivefold for patients with ALL compared with the general population. RTW was 41.7%, 65.7%, and 60.7% one, three, and five years after the index date, respectively. Conclusion: The risk of DP in patients with ALL increased significantly compared with the general population. Five years after the index date, RTW was 60.7% for patients with ALL.

Purpose: Many patients diagnosed with lymphoma are of working age. Cancer patients are known to have a higher risk of sick leave and disability pension, but this has only been delineated for certain subtypes of lymphoma. Therefore, this study aimed at investigating the overall risk of disability pension for all lymphoma subtypes and at quantifying return to work for patients with lymphoma in work before diagnosis. Patients and Methods: Patients aged 18– 60 years with lymphoma in complete remission (CR) diagnosed between 2000 and 2019 were included in the study. Using national registers, each patient was matched with five comparators from the general population with same sex, birth year, and level of Charlson Comorbidity Index. Risk of disability pension was calculated from 90 days after CR or end of treatment with competing events (death, retirement pension, early retirement pension, relapse for patients, or lymphoma diagnosis for comparators). Return to work for patients was calculated annually until 5 years after diagnosis for patients employed before diagnosis. Results: In total, 4072 patients and 20,360 comparators were included. There was a significant increased risk of disability pension for patients with all types of lymphoma compared to the general population (5-year risk difference: 5.3 (95% confidence interval (CI): 4.4;6.2)). Patients with non-Hodgkin lymphoma were more likely to get disability pension than patients with Hodgkin lymphoma (sex- and age-adjusted 10-year risk difference: 2.9 (95% CI: 0.3;5.5)). One year after diagnosis, 24.5% of the relapse-free patients were on sick leave. Return to work was highest 2 years after diagnosis (82.1%). Conclusion: Patients with lymphoma across all subtypes have a significantly higher risk of disability pension. Return to work peaks at 2 years after diagnosis.