Home care of acute leukaemia patients: From active therapy to end-of-life and palliative care. The 3-year experience of a single centre

Purpose: The aim of the study was to evaluate the feasibility and the potential effects of the Haematological Home Care (HHC) programme for acute leukaemia (AL) patients, either in active chemotherapy or in the terminal phase of disease. Methods: We retrospectively assessed a group of AL patients assisted at home in terms of number of hospitalisations, accesses to emergency department and place of death. We also used historical data to evaluate potential effects of HHC. Results: The study group consisted of 44 patients, 36 of whom (82%) required palliative treatment, and eight (18%) had ongoing active chemotherapy. The mean number of hospitalisations was 0.64 (range 0-7) per patient, and the number of emergency department (ED) visits was 0.82 (range 0-4) per patient. Place of death was at home for 51.4% of patients and in hospital for 40.5%. Considering a historical group of 17 patients assisted at home the rate of hospitalisations and ED visits were 2.53 (range 0-9) and one (range 0-3), respectively. Place of death was home and hospital in 6% and 65%, respectively. Conclusions: Haematological Home Care for AL patients is feasible and has potential positive effects in terms rate of hospitalisations and place of death

CCL20/CCR6 chemokine/receptor expression in bone tissue from osteoarthritis and rheumatoid arthritis patients: different response of osteoblasts in the two groups

Subchondral bone remodeling in osteoarthritis (OA) and rheumatoid arthritis (RA) is mainly characterized by the formation of osteophytes/fibrosis and by the presence of infiltrating cells associated to bone resorption. In this study we analyzed CC (cysteine cysteine motif) chemokine ligand (CCL)20 and CC chemokine receptor (CCR)6 function in subchondral bone tissue and osteoblasts isolated from OA and RA patients. CCL20/CCR6 expression was evaluated by immunohistochemical techniques in bone tissue from OA and RA patients. CCL20-functional tests were performed on osteoblasts isolated from OA and RA patients to evaluate enzymatic response and cell proliferation. Moreover, we assessed Akt phosphorylation as the major signaling pathway for CCL20. In bone tissue biopsies we found that osteoblasts from both OA and RA patients expressed CCR6 while CCL20 was expressed only by RA osteoblasts. Both CCR6 and CCL20 were highly expressed in osteocytes and mononuclear cells from only RA patients. CCL20-stimulated OA osteoblasts showed a significant increase in beta-N-acetylhexosaminidase release compared to RA. Conversely, a significant increase in cellular proliferation was found only in CCL20-stimulated RA osteoblasts associated to Akt phosphorylation. These data were confirmed in bone tissue biopsies. This study demonstrates a different expression of CCL20-positive osteoblasts in OA versus RA disease that seem to be associated with the presence of infiltrating mononuclear cells. Moreover, CCL20 stimulation resulted in a greater proliferative response in RA osteoblasts compared to OA osteoblasts, mediated by Akt signaling, while OA osteoblasts showed increased enzymatic activity, thus suggesting a differential role of this chemokine in OA and RA

Anagrelide treatment and cardiovascular monitoring in essential thrombocythemia. A prospective observational study

In this prospective observational single-center study, 55 patients with essential thrombocythemia who were candidates for second line treatment with anagrelide (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure, heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in-depth CV screening, 54 out of 55 patients were deemed to be fit for ANA treatment. Thirty-eight of the 55 patients received ANA treatment for a median of 36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2 arterial hypertension, 2 acute myocardial infarction) that were not predicted by the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non-cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did not appear to be necessary in ET patients to evaluate their suitability for ANA treatment, and, moreover, was not able to predict the occurrence of CV adverse events during ANA treatment. Nevertheless, the CV adverse events (mostly palpitations and edema) were easily managed by the hematologists, and required the cardiologist involvement in very few selected cases

Association of IMWG frailty score with health-related quality of life profile of patients with relapsed refractory multiple myeloma in Italy and the UK: a GIMEMA, multicentre, cross-sectional study

Background The clinical management of patients with relapsed or refractory multiple myeloma is challenging and there is a paucity of tools to help clinicians make more informed decisions for the most suitable treatment options. We aimed to investigate the clinical utility of the International Myeloma Working Group (IMWG) frailty score in the setting of relapsed or refractory multiple myeloma, by examining its ability to capture different patient-reported health-related quality of life profiles. Methods We did a cross-sectional analysis of a prospective observational study of patients with relapsed or refractory multiple myeloma in Italy and the UK (30 hospitals across northern, central, and southern Italy, and one hospital in London, UK). Inclusion criteria were age 18 years or older and patients who had received at least one previous line of therapy and no more than five lines. Participants were excluded if they had a psychiatric disorder or major cognitive dysfunction, or any grade 3 or higher adverse event within 2 weeks before study entry. On study initiation, physicians had to assess frailty according to the IMWG criteria, which included the Charlson Comorbidity Index, the Katz Activity of Daily Living, and the Lawton Instrumental Activities of Daily Living. Patients were asked to complete patient-reported outcome measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) and its validated multiple myeloma module (QLQ-MY20). A multivariable linear regression model was used to assess the mean differences in health-related quality of life scores between frailty groups to account for key potential confounding factors. Findings Overall, between Nov 13, 2017, and Nov 15, 2021, 415 patients with relapsed or refractory multiple myeloma, with a median age of 69 center dot 8 years (IQR 62 center dot 8-75 center dot 2) were enrolled. The median time since diagnosis was 4 center dot 4 years (IQR 2 center dot 5-7 center dot 1) and most patients (351 [85%]) had received at least two previous lines of therapy. According to the IMWG frailty score, 200 (48%) were classified as fit, 112 (27%) were classified as intermediate-fit, and 103 (25%) patients were classified as frail. Each frailty group was associated with a distinct health-related quality of life profile, with most notable differences between fit and frail patients. The largest clinically meaningful adjusted differences between fit and frail patients by the EORTC QLQ-C30 questionnaire were observed for physical functioning (Delta=-19 center dot 0 [95% CI -25 center dot 6 to -12 center dot 5; p<0 center dot 0001), fatigue (Delta=16 center dot 7 [9 center dot 7 to 23 center dot 7]; p<0 center dot 0001), insomnia (Delta=13 center dot 4 [4 center dot 1 to 22 center dot 6]; p=0 center dot 0047), and dyspnoea (Delta=12 center dot 5 [4 center dot 6 to 20 center dot 4]; p=0 center dot 0021). The most prevalent clinically important symptom in the overall population was pain; however, its prevalence varied between IMWG frailty groups at 70 center dot 9% in frail patients, 55 center dot 9% in intermediate-fit patients, and 50 center dot 5% in fit patients. Interpretation Our findings show the clinical utility of the IMWG frailty score in the setting of relapsed or refractory multiple myeloma, in helping to distinguish between groups of patients with distinct health-related quality of life profiles. Further research is needed to examine the value of patient-reported outcome data in improving assessment of frailty in the setting of relapsed or refractory multiple myeloma

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality.

OBJECTIVES We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. METHODS Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). RESULTS The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. CONCLUSIONS Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality

Pharyngeal microbial signatures are predictive of the risk of fungal pneumonia in hematologic patients

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.This work was supported by FunMeta Project (ERC-2011-AdG 293714), MicroTher(ERC-2018-PoC-813099), and Gilead (IN-IT-131-4525-518872.9) to L.R. and the GrantAgency of the Czech Republic (GACR No 17-24592Y) and the Czech Ministry ofEducation, Youth and Sports (CETOCOEN PLUS CZ.02.1.01/0.0/0.0/15_003/0000469;LM2015051 and CETOCOEN EXCELLENCE Teaming 2 project CZ.02.1.01/0.0/0.0/18_046/0015975; and Horizon2020 project 857560) to Z.S