Different response to imatinib and nilotinib in relationship with the time of administration

Here we describe a case of a young patient with chronic myeloid leukemia at low risk, according to the Sokal index. After cytoreduction with hydroxyurea, the patient started imatinib at standard dose (400 mg/day) obtaining a minor cytogenetic response (Ph+ 42.5%) after six months of treatment.Considering the low imatinib concentration evaluated with the blood level testing, we increased the dose of imatinib at 600 mg/day. After about 3 months treatment the patient presented a partial cytogenetic response (Ph+ 30%). Therefore he was considered suboptimal responder according to European LeukemiaNet (ELN) recommendations 2006. For this reason he switched to second generation tyrosine kinase inhibitor nilotinib, at dose 800 mg/die. After switching to nilotinib the patient reached complete cytogenic response and major molecular response, maintained until last molecular evaluation.This kind of patient shows a different response for imatinib and nilotinib, whereas nilotinib therapy has shown to be safe and efficacy

Mean reticolocyte hemoglobin content index plays a key role to identify children who are carriers of β –thalassemia

Reticulocyte (r) and red blood cell (RBC) indices provide reliable parameters for screening and monitoring iron deficiency anemia (IDA) patients and β-thalassemia trait (BTT) carriers. The aim of this study is to identify a simple method for use to distinguish β-thalassemia trait carriers from IDA and to evaluate the correlation between BTT genetic mutation and MCV values and new discrimination index for the detection of β-thalassemia trait (DI-BTT). We analyzed CHr, MCHCr, MCVr, RBC, mean cellular hemoglobin concentration (MCHC) and mean cellular volume (MCV) indices among a pediatric population of IDA patients (n=90), βthalassemia trait carriers (n=72) and normal controls (NC) (n=131). Furthermore, to distinguish IDA patients from β-thalassemia trait carriers we evaluated clinical utility of new DI for the detection BTTcarriers, using the following polynomial: (RBC × MCHC × 50/MCV)/CHr. We found that CHr, MCVr and DI-BTT mean values were significantly different between βthalassemia trait carriers and IDA patients. CHr, MCVr and DI-BTT plotting curves showed exclusive distribution in β-thalassemia trait carriers. Moreover, DI-BTT was very accurate in differentiating β-thalassemia trait carriers from IDA patients. All BTT patients showed a heterozygous mutation of the β-globin gene including CD39, IVS1.110, IVS1.6 and IVS2.745, IVS2.1 and IVS1.1. The highest MCV values were displayed by those carrying the IVS1.6 mutation. Conclusions: The simultaneous measurement and plotting of CHr and MCVr indices, as well as the DI-BTT allow to distinguish β-thalassemia carriers from IDA patients

Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients

Therapeutic approach for chronic myeloid leukemia (CML) patients has undergone a revolutionary change with the introduction of tyrosine kinase inhibitors, which improved overall survival and quality of life. Optimal therapy adherence has become of paramount importance to maximize the benefits in the long-term outcome. Several evidences have been reported that personal factors, such as social support, psychological and subjective perceptions about the drug used and the future, could influence adherence. We here report the results of a questionnaire specifically designed to evaluate factors influencing adherence and perceptions about the future, distributed to patients during regional Italian meetings. Overall, 1133 patients compiled the questionnaire: median age was 57 years. High rate of adherence was reported, but 42% of interviewed patients admitted that they had occasionally postponed a dose and 58% had discontinued therapy mainly for forgetfulness. The majority of patients discussed with personal physician about the importance of adherence and received sufficient information about illness and treatment, but would like to have discussed more about discomfort, anxiety and fear of the future. Summarizing personal drug compliance and estimating how many days a month, on average, the patients did not take the drug, the majority answered that it was less than 3 days (55%) and only a minority (4%) admitted that it was more than 7 days. Interviewed about discontinuation, 49% of patients answered that wouldn't interrupt because of fear of losing all the results achieved so far. This study suggests a higher level of satisfaction with more information received but the need of improving communication about possible future treatment free remission

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Monitoraggio ematologico mediante determinazione dell'AchE e del Tfr, quali biomarkers di danno tossico da pesticidi nel ratto.

Obiettivi. Sono state studiate le alterazioni ematologiche prodotte da danno tossico indotto in ratti Wistar dall’assunzione di DDE con la dieta, mediante monitoraggio dei parametri ematologici e l'identificazione di biomarkers, quali l’acetilcolinesterasi (AchE) e il recettore per la transferrina (TfR) sulle cellule eritroidi. Materiali e metodi. Ratti Wistar di sesso maschile, di 60 giorni di età e del peso di 400 g, suddivisi in 4 gruppi sperimentali sottoposti rispettivamente a: 1) dieta iperlipidica (40% in grassi) associata a trattamento con DDE (10 mg/Kg per peso corporeo) per 4 settimane (T2); 2) dieta standard (10% in grassi) associata a DDE (10 mg/Kg per peso corporeo) per 4 settimane (T2); 3) dieta iperlipidica (40% in grassi) associata a trattamento con DDE (10 mg/Kg per peso corporeo) per 4 settimane (T2) seguite da 2 settimane di dieta di restrizione (T3); 4) dieta standard (10% in grassi) associata a DDE (10 mg/Kg per peso corporeo) per 4 settimane (T2) seguite da 2 settimane di dieta restrizione (T3). Monitoraggio ematologico su campioni di sangue con litio eparina: determinazione spettrofotometrica dell’Hb, microematocrito, conta cellulare in camera di Bürker, formula leucocitaria, indici eritrocitari, analisi spettrofotometrica dell’AchE, rivelazione in immunocitochimica e in immunofluorescenza dell’AchE e del TfR su apposizioni midollari prima (T0) e dopo (T2-T3) trattamento con DDE. Risultati. Nei ratti di tutti i gruppi sperimentali, tra tempo iniziale (T0) e tempo finale (T2-T3) si è osservato: diminuzione della concentrazione di Hb, dell’Ht, del numero degli eritrociti e dei leucociti, dell’MCHC, e un aumento dell’MCV e dell’MCH; diminuzione dell’attività dell’AchE; riduzione della immunopositività dell’AchE e aumento della immunopositività del TfR nelle cellule eritroidi midollari. Conclusioni. L’assunzione del DDE con la dieta induce anemia macrocitica e citopenia periferica probabilmente conseguente a danno tossico midollare. Inoltre, la riduzione dell’attività enzimatica dell’AchE, la ridotta positività dell’AchE e l’aumentata positività del TfR a seguito di trattamento con DDE, suggeriscono che sia l’AchE che il TfR possano essere impiegati come markers di danno tossico da pesticidi

Nucleated red blood cells and soluble transferrin receptor in thalassemia syndromes: relationship with global and ineffective erythropoiesis

Background: The technology to recognize nucleated red blood cells (NRBC) automatically has only recently been developed. Modern hematology analyzers allow for rapid and accurate NRBC counts. The goal of our study was to evaluate NRBC counts and the concentrations of serum transferrin receptor (sTfR) in patients affected by different thalassemia syndromes and hereditary spherocytosis. We wished to gain a better understanding of the meaning of the presence of NRBC in peripheral blood and the relationship of the two parameters with effective and ineffective erythropoiesis in the different thalassemia syndromes. Methods: NRBC counts in peripheral blood were evaluated in a large group of patients with thalassemia (36 thalassemia major, 55 thalassemia intermedia and 61 Sβ-thalassemia patients) and compared with data from 29 patients with hereditary spherocytosis; in all the patients the concentration of sTfR was evaluated as an index of global erythropoiesis. Results: The NRBC count showed a good relationship with ineffective erythropoiesis: highest counts were observed in the thalassemia syndromes characterized by almost completely ineffective erythropoiesis. NRBCs were absent in patients affected by hereditary spherocitosis, a disease characterized by effective erythropoiesis. Conclusions: The NRBC count can be useful for better defining ineffective erythropoiesis in patients with thalassemia, and can help optimize transfusion therapy in severe thalassemia syndromes. Clin Chem Lab Med 2009;47:1539–42.Peer Reviewe

WENEMOR: Wind tunnel tests for the evaluation of the installation effects of noise emissions of an open rotor advanced regional aircraft

This paper presents the key objectives from an European Union funded collaborative project investigating the noise installation effects for novel regional advanced aircraft concepts using Open Rotor (OR) propulsion systems. The consortium for the project:WENEMOR, will address the topic by carrying out aero-acoustic measurements in the open test section of a large low speed wind tunnel using a complete reduced scale modular model of different configurations of an aircraft with installed counter rotating open rotor systems operating in both pusher and tractor modes. The principal goal of the project is to assess experimentally the noise shielding effectiveness of classic airframe components for different Open Rotor aircraft configurations. A complete 1/7th scale aircraft has been designed and built for installation in the Pininfarina Aerodynamic and Aeroacoustic Research Center Wind Tunnel. The model has two Open Rotors with a contra-rotating fan at the same scale as the airframe. Various positions of the ORs with respect to the airframe will be tested with noise measurements being performed both in the near and the far field. The test campaign will provide, for the first time in Europe, a comprehensive database on noise installation effects for novel regional advanced aircraft concepts using OR propulsion systems. Two accompanying conference papers present preliminary result