Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL.

Prognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1(T315I) was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL. Monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.

Long-term safety and efficacy of imatinib mesylate (Gleevec®) in elderly patients with chronic phase chronic myelogenous leukemia: results of the AFR04 study.

Data from registries suggest that the median age of chronic myelogenous leukemia (CML) patients is 10-15 years older than that of clinical trials. We conducted a prospective phase II study to evaluate imatinib mesylate (IM, 400 mg daily) in newly diagnosed chronic phase CML (CP-CML) patients. Patients aged 70 years and over diagnosed with CP-CML within 12 months were eligible. Thirty patients were enrolled from April 2002 to October 2004. Median age was 74.8 years (range, 70-90). Male/female ratio was 1.72. At inclusion, comorbidities were reported in all but one patient, Cumulative Illness Rating Scale for Geriatrics comorbidity mean index was 1.47, and 66% of patients had cardiovascular disease. The median daily IM dose was 392 mg (range, 256-445). IM was interrupted in patients with severe comorbidities. Treatment discontinuation was observed in 36.6% of patients. Cumulative incidence of complete cytogenetic response was 71.4 and 78.5% at 12 and 24 months, respectively. A high level of sustained responses was observed in patients with mild or moderate comorbidities. Seven-year estimated overall survival was 80.8% (95% CI: 59.0-91.7). Two-thirds of the patients were still on long-term therapy at cut-off, and no patients had died from progression. This trial was registered at http://www.clinicaltrials.gov as # NCT00219765.

[Management of congestive heart failure in the elderly after hospitalization for acute decompensation Interest of a dedicated territorial geriatric network ; the GERICCO-78 study]. / Prise en charge de l'insuffisance cardiaque chronique chez le sujet âgé fragile après hospitalisation pour décompensation aiguë ; apport d'une cellule de coordination ville-hôpital ; étude GERICCO-78.

AIMS: Heart failure (HF) is the leading cause of hospitalisation in the elderly in France. Early rehospitalisations are common, often through an emergency department. The aim of this study was to assess the impact of a primary care-hospital coordination network, with interventions by coordination nurses (IDEC), on the rehospitalisations after a first hospitalisation for acute decompensation in frail elderly HF patients. METHODS: From 01/10/2019 to 01/10/2021, 237 patients aged > 75 years with frailty criteria, hospitalised in 8 departments of 5 private or public hospitals in the Yvelines Sud health territory were followed by an IDEC (hospital visit, telephone contacts, home visit(s)) within 3 months of their return home. This prospective observational study analysed the rate of consultations to the emergency room, rehospitalisations (total and for acute HF), and the number of events avoided at 90 days after discharge. RESULTS: The mean age of the patients was 87 years, 54% were women, 68% had a left ventricular ejection fraction > 40%, and 70% had atrial fibrillation. Non-cardiac comorbidities were very frequent. At 3-month follow-up, mortality was 9.3% (22/237), only 27 patients (11.3%) consulted the emergency room for acute HF, and the rehospitalisation rate for HF was 19.8%, without difference according to left ventricular ejection fraction. A consultation to the emergency room or a rehospitalisation for heart failure could be avoided for 10% of patients. CONCLUSION: This study suggests that a primary care-hospital coordination network with dedicated coordination nurses is useful for the management of very elderly frail patients following hospitalisation for heart failure, limiting visits to the emergency room and rehospitalisations.

[Management of pneumonia in the elderly]. / Prise en charge d'une pneumonie du sujet agé.

Pneumonias in elderly are frequent and severe. They require an accurate assessment following clinical, biological and radiological steps. Each of them can contribute to give answers to the following questions: does this patient need emergency hospitalisation? Is the infection really bacterial and pulmonary? Should antibiotics be started? Which others treatments should be associated for the infection itself and for comorbid conditions? Concerning prevention, every effort must be done to decrease the incidence of these infections, especially vaccination. Pulmonary infections in nursing home need specific attention: cumulation of bad prognosis factors, risk of epidemic propagation, and vaccination of all people caring patients when required.

Fall related to epileptic seizures in the elderly.

It is well known that both falls and epileptic seizures are very frequent and harmful in the elderly. Moreover, although seizures may cause falls, their relationship is poorly documented in this population. We report four women (mean age: 84.5 years) who presented falls with: late-onset focal seizures of possible parietal (Case 1) or frontal localisation (Case 2), early onset with late aggravation of juvenile myoclonic epilepsy (Case 3), and generalised situation-related myoclonic seizures (Case 4). Falls were presumably associated with tonic posturing of left (Case 1) or right (Case 2) hemibody, to bilateral and massive myoclonic jerks (Cases 3 and 4) with a loss of consciousness (Case 3). The diagnosis of seizures was difficult and routine EEG was unremarkable in Cases 1 and 2, requiring video-EEG monitoring to capture the clinical events. Adequate treatment offered recovery from seizures and falls in all patients. Other mechanisms of seizure-induced falls in older patients and their management are discussed. In conclusion, falls may be caused by different seizure types and appear to be underestimated due to difficulties in seizure diagnosis in the elderly. Recognizing falls related to seizures is important in geriatric practice, as it facilitates adequate management.

Leukocyte Telomere Length in Alzheimer's Disease Patients with a Different Rate of Progression.

BACKGROUND: Age and short leukocyte telomeres have been associated with a higher risk of Alzheimer's disease (AD). Inflammation is involved in AD and it is suggested that anti-inflammatory interleukin-10 (IL-10) may partly antagonize these processes. OBJECTIVE: The aim is to correlate telomere length (TL) in peripheral blood mononuclear cells (PBMC) from patients with AD to disease progression rate. Moreover, we evaluated whether TL was associated with IL-10 production by unstimulated or amyloid-ß (Aß)-stimulated PBMC. METHODS: We enrolled 31 late-onset AD and 20 age-matched healthy elderly (HE). After a two-year follow-up period, patients were retrospectively evaluated as slow-progressing (ADS) (Mini Mental State Examination (MMSE) decline over the two years of follow-up ≤3 points) or fast progressing AD (ADF) (MMSE decline ≥5 points). TL was measured by flow cytometry and in vitro IL-10 production by enzyme-linked immunosorbent assay. RESULTS: TL (mean±SD) for HE, ADS, and ADF was 2.3±0.1, 2.0±0.1, and 2.5±0.1 Kb, respectively. ADS showed a shorter TL compared to HE (p = 0.034) and to ADF (p = 0.005). MMSE decline correlated with TL in AD (R2 = 0.284; p = 0.008). We found a significant difference in IL-10 production between unstimulated and Aß-stimulated PBMC from ADS (40.7±13.7 versus 59.0±27.0; p = 0.004) but not from ADF (39.7±14.4 versus 42.2±22.4). HE showed a trend toward significance (47.1±25.4 versus 55.3±27.9; p = 0.10). CONCLUSION: PBMC from ADF may be characterized by an impaired response induced by Aß and by a reduced proliferative response responsible for the longer telomeres. TL might be a contributing factor in predicting the rate of AD progression.

Interleukin-10 Production in Response to Amyloid-ß Differs between Slow and Fast Decliners in Patients with Alzheimer's Disease.

We investigated IL-10 and IL-6 production in amyloid-ß (Aß) stimulated peripheral blood mononuclear cells (PBMCs) in twenty Alzheimer's disease (AD) patients with slow progression, eleven with fast progression, and twenty age-matched controls. Promoter polymorphisms in IL-10 (position -592, -819, -1082), IL-6 (-174), transforming growth factor-ß1 (TGF-ß1) (-10, -25), interferon-γ (IFN-γ) (-874), and tumor necrosis factor-α (TNF-α) (-308) genes were analyzed. IL-10 production after Aß stimulation was high in PBMCs from slow decliners and almost completely abrogated in fast decliners. Association between AA IFN-γ low-producing genotype and fast progression was demonstrated. Investigations in a larger sample will clarify these findings.