Background:
One of the main obstacles of providing home-based palliative care to transfusion-dependent hematology patients is the lack of home transfusions services. While healthcare professionals ...are concerned with safety and cost of home transfusions, the attitude of the patients toward home transfusions are mostly unknown.
Aim:
To obtain quantitative data regarding the willingness and concerns of transfusion-dependent patients with hematological diseases toward the option of home transfusions.
Design:
A cross sectional survey including a self-administered questionnaire in one of the three main spoken languages in Israel was administered to patients in 17 hospital hematology outpatient clinics between May 2019 and March 2020.
Results:
About 52% of 385 patients that participated in the survey preferred home transfusions to hospital transfusions. Gender, age, education, or type of disease were not associated with preference for home transfusions, nor were hospital location or its size. The likelihood to prefer home transfusions was significantly higher among the Hebrew-speakers and those who had not experienced adverse effects previously. The most significant factor associated with preference of home transfusions was a perceived negative effect of hospital-based transfusion on quality of life. The main reason to reject home transfusions was fear of possible adverse effects and concerns over losing contact with the medical staff at the treating hospital.
Conclusion:
These data suggest that a significant portion of transfusion-dependent patients in Israel view home transfusions as a preferred treatment option and that its successful implementation requires maintaining ongoing contact with the treating hospital.
Objectives
One third of CML patients treated with first line imatinib have suboptimal responses or treatment failures with increased risk for disease progression. Imatinib is actively transported ...into cells by the SLC22A1 transporter (hOCT1) and its genetic variants may affect intracellular drug import. We studied the effect of SLC22A1 genetic variants on long‐term outcomes of imatinib treated patients.
Methods
A total of 167 patients, 94% in chronic phase, were analyzed for rs41267797, rs683369, rs12208357, and rs628031 variants using the Sequenom MassARRAY platform.
Results
Rates of CHR, MCyR, CCyR, and MMolR were not significantly different according to allelic variants. However, patients with AA or GA rs628031 genotypes had a higher incidence of poor response to imatinib compared to the GG genotype (47% compared to 29%, P = 0.06), and a higher rate of KD mutation discovery (8/16 vs. 5/27, P = 0.04), suggesting that secondary resistance was more common in these genotypes. Median EFS was shorter for rs628031 genotype AA/AG compared with the GG genotype (61 months and not reached, respectively, P = 0.05), and 5 yr OS rates were lower for patients with the rs628031 genotypes AA/AG compared with the GG genotype (88% and 97%, respectively, P = 0.03). Patients with AA/GA rs628031 and additional rare genotypes had worse EFS and OS compared to patients with only AA/GA rs628031 (P = 0.02 for EFS and 0.01 for OS). There was no difference in pretreatment SLC22A1 mRNA expression levels in patients with rs628031 genotypes GG/AA or GA.
Conclusions
Studying SLC22A1 genetic variants prior to TKI initiation could influence treatment decisions.
Summary
Somatic point mutations in the PH domain of SH2B3 (LNK), an adaptor protein that is highly expressed in haematopoietic cells, were recently described in patients with myeloproliferative ...neoplasms. We studied the effect of these mutations on the JAK2 signalling pathway in cells expressing either wild type JAK2 or the JAK2 V617F mutation. Compared to wild type SH2B3, PH domain mutants have mild loss of function, with no evidence for a dominant‐negative effect. Mutants retain binding capacity for JAK2, an established SH2B3 target, as well as for the adaptor proteins 14‐3‐3 and CBL. Our data suggest that the loss of SH2B3 inhibitory function conferred by the PH domain mutations is mild and may collaborate with JAK2 V617F and CBL mutations in order to promote either the development or the progression of myeloproliferative neoplasms.
Transfusion guidelines advocate restrictive rather than liberal use of red blood cells (RBC) and are based mostly on randomized trials in intensive care and surgical departments. We aimed to study ...RBC transfusion practice in the medical patients' population.
The data in this study were collected from patients over the age of 18 years admitted to an Internal Medicine department between 2009 and 2014 who received at least one unit of packed red blood cells (RBC). In addition, data on demographics, patients' diagnoses, laboratory tests and number of transfused RBC units were extracted from the electronic health records.
One thousand three hundred and twenty eight patients were included, having mean age of 75 ± 14 years. The median hemoglobin (Hb) trigger for RBC transfusion was 8.0 g/dl (IQR 7.3-8.7g/dl), and most patients received either one (43.4%) or two (33.4%) RBC units. There was no significant difference in Hb trigger between males and females (Hb 8.0 g/dl and 7.9 g/dl, respectively, p = 0.098), and a weak correlation with age (r = 0.108 p = 0.001). Patients with cardiovascular and lung diseases had a statistically significant higher Hb trigger compared to patients without those diagnoses, however the median difference between them was 0.5 g/dl or less.
These "real world" data we collected show a Hb trigger compliant with the upper limit of published guidelines and influenced by medical patients' common diagnoses. Prospective trials addressing patients hospitalized in internal medicine departments could further contribute to transfusion decision algorithms.
Lnk physically interacts with c‐Fms and blunts its activity in‐cluding proliferation of macrophage progenitor cells, M‐CSF stimulated migration, and generaton of ROS.
The M‐CSFR (c‐Fms) participates ...in proliferation, differentiation, and survival of macrophages and is involved in the regulation of distinct macrophage functions. Interaction with the ligand M‐CSF results in phosphorylation of tyrosine residues on c‐Fms, thereby creating binding sites for molecules containing SH2 domains. Lnk is a SH2 domain adaptor protein that negatively regulates hematopoietic cytokine receptors. Here, we show that Lnk binds to c‐Fms. Biological and functional effects of this interaction were examined in macrophages from Lnk‐deficient (KO) and WT mice. Clonogenic assays demonstrated an elevated number of M‐CFUs in the bone marrow of Lnk KO mice. Furthermore, the M‐CSF‐induced phosphorylation of Akt in Lnk KO macrophages was increased and prolonged, whereas phosphorylation of Erk was diminished. Zymosan‐stimulated production of ROS was increased dramatically in a M‐CSF‐dependent manner in Lnk KO macrophages. Lastly, Lnk inhibited M‐CSF‐induced migration of macrophages. In summary, we show that Lnk binds to c‐Fms and can blunt M‐CSF stimulation. Modulation of levels of Lnk in macrophages may provide a unique therapeutic approach to increase innate host defenses.
The myeloproliferative neoplasms (MPN) are clonal diseases that confer an increased risk of thrombohemorrhagic complications. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease ...associated with an increased thrombotic risk. Small PNH clones are prevalent in aplastic anemia and myelodysplastic syndrome patients, but their prevalence in MPN patients is unknown.
Consecutive patients with MPN followed up at a single center were recruited. PNH clones were analyzed in erythrocytes and white blood cells by flow cytometry.
PNH clones were detected in 2% of patients and were more common in JAK2 V617F positive patients. We could not detect any differences in clinical manifestations or complications in patients either with or without PNH clones because of the small patient numbers.
The prevalence of PNH clones in MPN is similar to that described in myelodysplastic syndromes. Whether PNH clones influence MPN phenotype and complications should be studied prospectively in larger patient cohorts and over long-term follow-up.
Paroxysmal nocturnal hemoglobinuria (PNH) and myeloproliferative neoplasm (MPN) are diseases associated with increased thrombosis. PNH clones are commonly found in other hematologic diseases, such as myelodysplastic syndromes and aplastic anemia. The presence of PNH clones was studied in consecutive MPN patients. A prevalence of 2% and an association with the JAK2 mutation was found. Presence of a PNH clone could potentially influence the clinical course of MPN.
Macrophage activation syndrome is the most frequent life-threatening complication of adult-onset Still's disease. This is a nearly fatal case of a young patient, which has been refractory to ...corticoste- roids, anakinra, tocilizumab, cyclosporine A, and etoposide, but eventually responded miraculously to salvage therapy with ruxolitinib. We review recent pertinent data related to the therapeutic value of ruxolitinib for macrophage activation syndrome triggered by adult-onset Still's disease.
Nilotinib is active in imatinib-resistant and -intolerant chronic myeloid leukemia patients and was recently approved for these indications.
Data on the efficacy and safety of nilotinib treatment ...were collected from 2 phase 2 expanded access clinical trials with similar designs (CAMN107AIL01 and ENACT).
Of 88 study patients (58 chronic, 11 accelerated, 19 blast crisis), the best responses to nilotinib were complete hematologic response (CHR) in 27%, partial cytogenetic response in 12%, complete cytogenetic response in 14%, and major molecular response in 19%. Patients achieving at least a CHR during imatinib therapy were more likely to respond to nilotinib, and failure to achieve at least a CHR on imatinib therapy was predictive of progression or lack of response to nilotinib (P=.0021). Responses were not statistically different in subgroup analysis, including that of imatinib intolerance compared with imatinib resistance, presence of ABL kinase domain mutations compared with absence of mutations, and previous treatment with another second-generation tyrosine kinase inhibitor compared no prior treatment. The overall survival and progression-free survival rates at 1 year were 83% and 48% for the entire cohort, 93% and 66% in chronic phase, and 64% and 19% in advanced phase. Adverse hematological events included thrombocytopenia (all events, 27%; grade 3-4, 13%) and leukopenia (all events, 18%; grade 3-4, 10%). The majority of the nonhematological events were mild, the most common being rash, infection, bone pain, headache, nausea, and vomiting.
Nilotinib treatment is an efficient and safe therapy for imatinib-resistant or -intolerant patients. Prior response to imatinib therapy is a predictor for the response to nilotinib.
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