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In the last decade, the number of older patients undergoing allogeneic Hematopoietic Cell Transplantation (alloHCT) has increased substantially. Analyzing the long-term outcomes of these patients poses new methodological challenges since their population mortality (the risk of mortality that they would have faced in the absence of their disease and treatment) is non-negligible. Interpreting all non-relapse mortality (NRM) as treatment-related mortality cannot be justified in this older population. An additional problem in the analysis of the causes of death is that individual adjudication as to treatment-related complications is often impossible. Although more common in transplant recipients, both cardiac deaths and cancer also occur frequently in the general population in this age group. For these reasons, we propose to extend the analysis of standard outcomes with statistical methods to estimate the size of population- and treatment-related mortality in heterogeneous populations. We analyzed the outcomes of two large cohorts of patients whose data had been collected by the European Society for Blood and Marrow Transplantation: (1) myelodysplastic syndromes or secondary acute myeloid leukemia (n=6434, median age 56 years), and (2) chronic lymphocytic leukemia (n=2589, median age 55 years). We focused on patients who had survived for two years after alloHCT without relapse or progression. We used integrated methods from relative survival and multi-state models to estimate what proportion of mortality can be attributed to disease relapse and what to the expected general population mortality. A key assumption was that the risk of mortality of the patient cohorts, apart from that associated with the disease and its treatment, was similar to that of the age-, sex-, calendar year- and country-matched general population. The remaining mortality, excess non-relapse mortality, can then be interpreted as closely approximating to treatment-related mortality, where 'treatment' refers both to treatment prior to transplantation and to alloHCT and its sequelae. The figures illustrate the probabilities of these events for the MDS cohort. This non-parametric model was then extended to a Cox model where we also assessed the impact of age and other risk factors on the different components of mortality. Combining relative survival and multi-state models gives more insight into the different causes of mortality and the impact of age and other risk factors on them. We show that for older patients, a substantial part of NRM is actually attributable to population mortality, information which should hopefully lead to more informed discussions regarding the risk of alloHCT and improvement of long-term care. [ABSTRACT FROM AUTHOR]

When analysing patient survival, one is often interested in cause of death. Little is known about the presence of population mortality in advanced melanoma patients. The aim of this study was to assess population mortality after different response states in advanced melanoma patients in the Netherlands, and analyse the contribution of disease and population mortality for different age groups. We selected patients diagnosed between 2013 and 2019 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. A multi-state model with response states integrating population mortality was fitted. One-year landmark analyses were performed to assess outcomes after each response state. Overall, 5119 patients were selected. Five-year probabilities of melanoma-related mortality in patients alive in complete response at one year after diagnosis increased with age, and was 17.2% (95% confidence interval: 13.0–21.4) for patients aged <65 years and 28.7% (95% confidence interval: 24.3–33.1) in patients aged ≥80 years. Population mortality only played a large role for older patients (75 years and above) alive at 1 year after diagnosis with a partial or complete response. Even though survival outcomes of advanced melanoma patients have improved over the last decade, the vast majority of patients still die due to melanoma-related mortality. • Melanoma-related mortality after tumour responses has not been studied so far. • Using multi-state models, the prognostic impact of response states was assessed. • Melanoma-related mortality dominates population mortality in advanced melanoma. • Population mortality plays a role in patients ≥75 years who respond to therapy. [ABSTRACT FROM AUTHOR]

In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregional or distant recurrence in a population-based cohort of older patients analysed by multi-state models. Surgically treated patients ≥70 years diagnosed with stage I-III breast cancer in 2003–2009 were selected from the Netherlands Cancer Registry. A novel multi-state model with locoregional and distant recurrence that incorporates relative survival was fitted. Other-cause and breast cancer mortality were indicated as population and excess mortality. Overall, 18,419 patients were included. Ten-year cumulative incidences of locoregional and distant recurrence were 2.8% (95%CI 2.6–3.1%) and 12.5% (95%CI 11.9–13.1%). Other-cause mortality increased from 23.9% (95%CI 23.7–24.2%) in patients 70–74 years to 73.8% (95%CI 72.2–75.4%) in those ≥80 years. Ten-year probabilities of locoregional or distant recurrence with subsequent breast cancer death were 0.4–1.3% and 10.2–14.6%, respectively. For patients with a distant recurrence in the first two years after diagnosis, breast cancer death probabilities were 95.3% (95%CI 94.2–96.4%), 93.1% (95%CI 91.6–94.6%), and 88.6% (95%CI 86.5–90.8%) in patients 70–74, 75–79, and ≥80 years. In older patients without recurrence, prognosis is driven by other-cause mortality. Although locoregional recurrence is a predictor for worse outcome, given its low incidence it contributes little to breast cancer mortality after diagnosis. For patients who develop a distant recurrence, breast cancer remains the dominant cause of death, even at old age. • Older patients with breast cancer often die from competing causes. • Competing mortality after recurrence has not been extensively studied so far. • Novel multi-state models were used including time after recurrence. • These models can be applied to different datasets as input for clinical decision tools. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the short-term efficacy and safety of antithymocyte globulin treatment (ATG) in elderly patients with acquired aplastic anaemia. Also cited are the combined horse-derived ATG and ciclosporin (CSA) as standard first-line immunosuppressive therapy (IST) for the disease, and the results showing that age should not be an absolute contraindication for using ATG and CSA to treat older patients with acquired aplastic anaemia.