Background: ITP incidence is known to increase in adults aged >60 years and even more in men aged >75 years (Moulis G et al., Blood 2014; 124(22):3308). As population aging and life-expectancy continues to increase worldwide, ITP in the elderly is a growing concern in everyday clinical practice. There are only a few studies regarding the features of ITP in patients (pts) aged >60-65 years and data are even scarcer in pts aged ≥75 years Aims: To describe real world characteristics at diagnosis and evaluate disease outcome in a group of pts aged 60-74 years (Group-1) as compared to very old pts (≥75 years; Group-2) with primary ITP, using data from the national database (ITP registry) operated under the auspices of the Hellenic Society of Hematology Methods: The Greek ITP registry recruits pts (n=1560, to date) nationally through a network of 25 sites. In the present study we retrospectively analyzed data from pts with primary ITP aged ≥60 years, who were diagnosed from 1979 to 2021. Results: The total number of evaluable pts was 298. Group-1 consisted of 180 and Group-2 of 118 pts. The mean age at diagnosis was 68 years (60.1-74.9) in Group-1 and 81 years (75.2-97.1) in Group-2. The female to male ratio did not differ between the 2 groups. The median platelet count at diagnosis was significantly higher in Group-1 (20x109/L, interquartile range: 5-44x109/L) than in Group-2 (11x109/L, interquartile range: 5-32x109/L; P=0.0096). Comorbidity rates did not differ between Group-1 and Group-2, with the exception of hypertension and chronic kidney disease, which were less frequently reported in Group-1 (P=0.0092 and P=0.0179, respectively). Concurrently used medications as a whole and also vitamin-K antagonists were reported less frequently in Group-1 (P=0.03 and P=0.049, respectively). Bleeding manifestations at diagnosis were comparable across the two age-groups. The choice of diagnostic procedure did not differ between Goup-1 and Group-2, with the exception of anti phospholipid antibody and anti nuclear antibody testing which were performed more frequently in Group-1 (P=0.048 and P=0.0002, respectively). Similar rates of positive laboratory test results were reported in the two age-groups. Fewer pts received treatment at diagnosis in Group-1 (P=0.023). Overall response rate did not differ between the two Groups. A similar proportion of Group-1 and Group-2 patients were treated with corticosteroids, intravenous IgG or both, rituximab, anti-D, immunoglobulin or thrombopoietin receptor agonists. Splenectomy was performed in 2.8% of Group-1 pts but in none of Group-2 pts. At 1 year after diagnosis, a similar proportion of Group-1 and Group-2 pts had developed chronic ITP. Summary/Conclusion: Very elderly pts (Group-2) presented with lower platelet counts at diagnosis and required ITP treatment more frequently than elderly pts (Group-1). Furthermore, Group-2 pts suffered more often from hypertension and chronic kidney disease and used more often anticoagulant agents. On the other hand, the 2 age-groups did not differ in the frequency or the location of bleeding. Age did not seem to particularly influence the diagnostic workup or the choice of treatment, with the exception of splenectomy which was not performed in Group-2 patients. The outcome of the disease was comparable in the 2 age-groups, as suggested by the similar treatment response rates and chronic ITP frequencies. Further investigation is warranted to full characterize the very elderly pts with ITP and unravel the unmet need of this cohort in order to optimize management.
Abstract Background Patients with higher-risk (HR) myelodysplastic syndrome (MDS), ineligible for allogeneic hematopoietic stem cell transplantation (alloHSCT), require prompt therapeutic interventions, such as treatment with hypomethylating agents (HMAs) to restore normal DNA methylation patterns, mainly of oncosuppressor genes, and consequently to delay disease progression and increase overall survival (OS). However, response assessment to HMA treatment relies on conventional methods with limited capacity to uncover a wide spectrum of underlying molecular events. Methods We implemented liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess 5’ methyl-2’ deoxycytidine (5mdC), 5’ hydroxy-methyl-2’-deoxycytidine (5hmdC) levels and global adenosine/thymidine ([dA]/[T]) ratio in bone marrow aspirates from twenty-one HR MDS patients, pre- and post-HMA treatment. Additionally, targeted methylation analysis was performed by interpretation of NGS-methylation (MeD-seq) data obtained from the same patient cohort. Results LC/MS-MS analysis revealed a significant hypomethylation status in responders (Rs), already established at baseline and a trend for further DNA methylation reduction post-HMA treatment. Non-responders (NRs) reached statistical significance for DNA hypomethylation only post-HMA treatment. The 5hmdC epigenetic mark was approximately detected at 37.5–40% among NRs and Rs, implying the impairment of the natural active demethylation pathway, mediated by the ten-eleven (TET) 5mdC dioxygenases. R and NR subgroups displayed a [dA]/[T] ratio < 1 (0.727 − 0.633), supporting high frequences of 5mdC transition to thymidine. Response to treatment, according to whole genome MeD-seq data analysis, was associated with specific, scattered hypomethylated DMRs, rather than presenting a global effect across genome. MeD-seq analysis identified divergent epigenetic effects along chromosomes 7, 9, 12, 16, 18, 21, 22, X and Y. Within statistically significant selected chromosomal bins, genes encoding for proteins and non-coding RNAs with reversed methylation profiles between Rs and NRs, were highlighted. Conclusions Implementation of powerful analytical tools to identify the dynamic DNA methylation changes in HR MDS patients undergoing HMA therapy demonstrated that LC-MS/MS exerts high efficiency as a broad-based but rapid and cost-effective methodology (compared to MeD-seq) to decode different perspectives of the epigenetic background of HR MDS patients and possess discriminative efficacy of the response phenotype to HMA treatment.
Background: The landscape of first-line treatment for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy has changed remarkably after venetoclax approval. Accumulating real-world data further apprises us with more knowledgeable use. To assess the efficacy and safety challenges in the real-life setting of the combination of hypomethylated agent (HMA) and venetoclax, we conducted a multi-center retrospective study. Methods: Forty adult AML patients treated with the combination of HMA and venetoclax as a first-line treatment after full approval (2020) were included. To confirm VIALE-A results, this group was compared to a historical cohort of 17 chemotherapy-ineligible AML patients treated with HMA monotherapy before 2020. Results: The combination of HMA-venetoclax achieved a composite complete response rate of 86.8% (p < 0.001), median overall survival, and event-free survival of 33.8 and 19.7 months, respectively, in a median follow-up of 17.8 months (pos < 0.001, HR = 0.276, CI: 0.132–0.575, pEFS = 0.004, HR = 0.367, CI: 0.174–0.773). High rates of neutropenia (90%) and consequent infection rates (57.5%) were noted. Only 55% of our patients received antifungal prophylaxis, as its use remains controversial, and invasive fungal infections were presented in 7.5%. Conclusions: Evidently, venetoclax-HMA yields high response rates and profound survival benefits in real life and has changed our approach to alternative chemotherapy options.
