Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is > 70 years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living and social support. Comorbidity scoring and geriatric assessment tools are helpful in achieving such multidimensional evaluation in a systematic manner. The introduction of new drugs including novel monoclonal antibodies and kinase inhibitors offers enhanced opportunities for the treatment of elderly patients with CLL. This position paper of a Task Force of the International Society of Geriatric Oncology (SIOG) reviews currently available evidence relevant to such patients. All types of elderly patient (i.e. chronological age > 65–70 years) are considered, from robust (fit) to vulnerable (unfit) to the terminally ill. Among the topics covered are the following: (i) the relationship between chronological age, prognosis and survival, (ii) assessment of biological aging, (iii) biological age as a determinant of treatment feasibility and tolerance and (iv) tailoring of both first and further-line treatment to the circumstances of the individual patient.

Background: Anemia in later life is associated with increased morbidity and mortality. The purpose of this study was to evaluate the prevalence and possible causes of anemia in the elderly in a well defined hospital cohort. Methods: Participants in this cross-sectional, retrospective analysis included all inpatients and outpatients aged ≥64 years with complete blood counts treated at Innsbruck Medical University Hospital between October 1, 2004 and September 29, 2005 (n=19,758, median age 73 years). Results: According to World Health Organization criteria, 21.1% of these patients were anemic, ie, 30.7% and 37.0% at 80+ years and 90+ years, respectively. The prevalence of anemia was significantly correlated with advanced age (r=0.21; P<0.001) and male sex (P<0.001). In anemic patients, renal insufficiency with a glomerular filtration rate <30 mL/min/1.73 m² (11.3% versus 2.1%), hyperinflammation (62.1% versus 31.4%), absolute (14.4% versus 6.9%) or functional (28.2% versus 11.8%) iron deficiency, and folate deficiency (6.7% versus 3.0%) were observed significantly more often than in nonanemic subjects (P<0.001). The pathogenesis of anemia was multifactorial, with decreased renal function (glomerular filtration rate <60 mL/min/1.73 m²), signs of inflammation, and functional iron deficiency detected in 11.4% of anemic patients. Hemoglobin was significantly correlated with elevated C-reactive protein (r=–0.296; P<0.001) and low transferrin saturation (r=0.313; P<0.001). Mean corpuscular volume correlated only weakly with the various anemia subtypes. Cytopenias and morphologic alterations suggestive of underlying myelodysplastic syndromes were found in a substantial proportion of anemic patients, including thrombocytopenia (5.4%), leukopenia (8.26%), and macrocytic alterations (18.4%). Conclusion: Anemia was frequently diagnosed in this series of elderly patients. Partly treatable nutritional deficiencies, such as iron or folate deficiency, were identified as possible causes. A complex and heterogeneous interplay of chronic inflammation, functional iron deficiency, and renal impairment was identified in a large proportion of patients. A hitherto undiagnosed myelodysplastic syndrome can be assumed in a relevant proportion of patients. Morphologic classification based on mean corpuscular volume is inadequate from the standpoint of pathogenesis. New parameters are needed to differentiate the multifactorial pathogenesis of anemia in the elderly.

In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (p < 0.001). In comparison to age- and sex-matched peers, the proportion of problems in usual activities and anxiety/depression was significantly higher in MDS patients (p < 0.001). MDS-related restrictions in the dimension mobility were most prominent in males, and in older people (p < 0.001); in anxiety/depression in females and in younger people (p < 0.001); and in EQ-VAS in women and in persons older than 75 years (p < 0.05). Patients newly diagnosed with IPSS lower-risk MDS experience a pronounced reduction in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with reference populations.

Myelodysplastic syndromes/neoplasms (MDS) are associated with variable clinical presentations and outcomes. The initial response criteria developed by the International Working Group (IWG) in 2000 have been used in clinical practice, clinical trials, regulatory reviews, and drug labels. While the IWG criteria were revised in 2006 and 2018 (the latter focusing on lower-risk disease), limitations persist in their application to higher-risk MDS and in their ability to fully capture clinical benefits of novel investigational drugs or to serve as valid surrogates for longer-term clinical endpoints (e.g., overall survival). Further, issues related to ambiguity and practicality of some criteria lead to variability in interpretation and inter-observer inconsistency in reporting results from the same sets of data. Thus, we convened an international panel of 36 MDS experts and used an established modified Delphi process to develop consensus recommendations for updated response criteria that would be more reflective of patient-centered and clinically relevant outcomes in higher-risk MDS. Among others, the IWG 2023 criteria include changes in the hemoglobin threshold for complete remission (CR), the introduction of CR with limited count recovery (CRL) and CR with partial hematologic recovery (CRh) as provisional response criteria, elimination of marrow CR, and specific recommendations for standardization of time-to-event endpoints and the derivation and reporting of responses. The updated criteria should lead to better correlation between patient-centered outcomes and clinical trial results in an era of multiple emerging new agents with novel mechanisms of action.

Objective: The Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios. Patients and methods: The sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed. Results: In this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001). Conclusions: In this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.