Physicians’ Perceptions of Clinical Utility of a Digital Health Tool for Electronic Patient-Reported Outcome Monitoring in Real-Life Hematology Practice. Evidence From the GIMEMA-ALLIANCE Platform

Digital health tools are increasingly being used in cancer care and may include electronic patient-reported outcome (ePRO) monitoring systems. We examined physicians’ perceptions of usability and clinical utility of a digital health tool (GIMEMA-ALLIANCE platform) for ePRO monitoring in the real-life practice of patients with hematologic malignancies. This tool allows for the collection and assessment of ePROs with real-time graphical presentation of results to medical staff. Based on a predefined algorithm, automated alerts are sent to medical staff. Participating hematologists completed an online survey on their experience with the platform. Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) agreed to enter the platform and had a median age of 57 years. Twenty-three hematologists with a median age of 42 years and an average of 17 years of experience in clinical practice were surveyed. All hematologists agreed or strongly agreed that the platform was easy to use, and 87%, agreed or strongly agreed that ePROs data were useful to enhance communication with their patients. The majority of physicians (78%) accessed the platform at least once per month to consult the symptom and health status profile of their patients. The frequency of access was independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). In conclusion, our preliminary results support the clinical utility, from the perspective of the treating hematologist, of integrating ePROs into the routine cancer care of patients with hematologic malignancies

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

BackgroundImatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. MethodsA total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. ResultsSecond-generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and & GE;3 concomitant medications. ConclusionsThis observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

Prevalence of allo-immunization anti-HLA and anti-integrin alpha IIb beta 3 in Glanzmann thromboasthenia patients

Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against human leucocyte antigen and integrin alpha IIb beta 3. We have investigated in our GT patients the rate of allo-immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.8 years (range 1-44.5); median age at the time of the study 35.5 years (range 23.6-68.5). In our patients, 121 bleeding episodes occurred (24 severe, 37 moderate, and 60 mild). Ten major and 22 minor surgical procedures have been performed. Two spontaneous deliveries and three caesarian sections with five live births were performed; moreover, one late foetal loss occurred, and one voluntary abortion was performed. Sixteen of 17 patients have been transfused at least once in life with platelets and/or red blood cells (RBC). All transfused patients have been investigated for the presence of anti-HLA and anti-integrin alpha IIb beta 3 allo-antibodies. The positiveness of allo-antibodies has been demonstrated in 4/16 transfused patients (25%): isolated for anti-HLA in two; isolated for anti-integrin alpha IIb beta 3 in one; and combined in one. In spite of the presence of allo-antibodies, platelet transfusions have always been effective and the haemostasis was not compromised

Clinical follow-up of 378 patients with autoimmune hemolytic anemia: prognostic impact of hemoglobin levels, autoantibody class, and reticulocytopenia at onset on the relapse risk and outcome

Autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening, due to autoantibody class/thermal amplitude and bone marrow compensatory response. Here we studied 378 patients (135 M and 243 F, median age 61 yrs, range 19-100), followed-up for 4.3 yrs (range 0.5-27), classified in warm (w)AIHA (DAT positive for IgG and IgG+C), cold agglutinin disease, CAD (C), mixed (IgG+C with high titer cold agglutinins) and atypical (DAT-, IgA+, wIgM). Anemia was categorized in Hb<6, 6-8, 8-10 and >10 g/dl, LDH expressed as fold upper the limit of normality (ULN) and reticulocytes as absolute count and index. The therapy lines were: steroids, rituximab, splenectomy, immunosuppressors, and transfusions/plasma exchange/erythropoietin. Hb was lower in IgG+C wAIHA and atypical cases (p<0.001), LDH higher in IgG+C wAIHA, mixed and atypical forms (p=0.01), and Hb and LDH values were negatively correlated (r=-0.25,p<0.001)[Table1]. Reticulocytes were lowerin CAD, mixed and IgG+C wAIHA (p<0.001) with inadequate reticulocytosis (p=0.01). Moreover, reticulocyte index was lower in cases with Hb<6 g/dL (p<0.001), with inadequate reticulocytosis (87 vs 70%,p=0.01).1st line therapy was administered in all cases but 25 CAD. 2nd line was mostly required in IgG+C wAIHA, mixed, and CAD (p=0.005). Ultra-refractory cases requiring 4 or> lines were mixed, atypical, and CAD. Patients with Hb<8 g/dL frequently required a 2nd line (51 vs 33%, p=0.004; p=0.03), or 3 or > lines (73% vs 26%, p<0.001). The following hazard ratios (HR) emerged from multivariate analysis: 3.2 (95% CI 1.4-7), 2.9 (1.4-6.2), 3.4 (1.6-7.5), for Hb<6, 6-8, and 8-10 g/dL compared to patients with Hb>10. Infections occurred in 14% of cases (mostly mixed AIHA, p=0.02), thrombosis in 10%, and acute renal failure (ARF) in 3% with no relationship with AIHA type/Hb. Evans\u2019 syndrome was frequent in mixed or atypical (p=0.04) and in severe forms (74% with Hb<8 g/dL vs 26%, p=0.005), and associated with higher relapse risk (HR 2.3, 95% CI 1.4-3.9). Seventy patients died, 12 because of AIHA complications. Mortality correlated with infections (HR 5.8),ARF (HR 7.6) and Evans\u2019 syndrome (HR 8.3). In conclusion, we found that anemia severity at onset was the major determinant of relapse risk. The lowest Hb levels were observed in patients with IgG+C WAIHA and atypical cases along with higher LDH levels and inadequate reticulocytosis, advising strict clinical observation in these patients

Clinical follow-up of 378 patients with autoimmune hemolytic anemia: prognostic impact of hemoglobin levels, autoantibody class, and reticulocytopenia at onset on the relapse risk and outcome

Background:Autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening, due to autoantibody class/thermal amplitude, efficiency in activating complement, activity of the reticuloendothelial system, and efficacy of bone marrow compensatory response. Aims: Here we analysed predictors of first relapse, complications, and fatality in a large AIHA series. Methods: We retrospectively studied 378 patients (135m and 243 F, median age 61 yrs, range 19-100) from 10 sites, followed-up for 4.3 yrs (range 0.5- 27). Patients were classified in warm (w)AIHA (DAT positive for IgG and IgG+C), cold agglutinin disease, CAD (C), mixed (IgG+C with high titer cold agglutinins) and atypical (DAT-, IgA+, wIgM). Cases were also grouped in very severe (Hb<6 g/dl), severe (Hb 6-8 g/dl), moderate (Hb 8-10 g/dl) and mild (Hb>10 g/dl). LDH was expressed as fold increase upper the limit of normality (ULN), and reticulocytes as absolute count and reticulocyte index. The following therapy lines were considered a) steroids +/-IvIg, b) rituximab c) splenectomy, d) immunosuppressive drugs (azathioprine, cyclophosphamyde, cyclosporin), and e) transfusions, plasma exchange, erythropoietinResults: Table 1 shows clinical and laboratory characteristics of AIHA cases at onset and distribution of thermal types. Hb values were significantly lower in IgG+C wAIHA and atypical cases (p<0.001), LDH higher in IgG+C wAIHA, mixed and atypical forms (p=0.01), and Hb and LDH values were negatively correlated (r= -0.25, p<0.001). Absolute reticulocytes were reduced in CAD, mixed and IgG+C wAIHA (p<0.001) together with inadequate reticulocytosis (p=0.01). Moreover, the reticulocyte index was lower in cases with Hb<6 g/dL (65 vs 98, p<0.001), along with more frequent inadequate reticulocytosis (87 vs 70%, p=0.01). First line therapy was administered in almost all cases but 25 CAD. A second therapy line was mostly required in IgG+C wAIHA, mixed, and to a lesser extent in CAD (p=0.005). The ultra-refractory cases requiring 4 or more lines of therapy were mainly mixed, atypical and CAD. Considering anemia severity, patients with Hb<8 g/dL more frequently required treatment after first-line (51 vs 33%, p=0.004; p=0.03), or even 3 or more therapy lines (52/71, 73% vs 19/71, 26%, p<0.001). The following hazard ratios (HR) emerged from multivariate Cox regression analysis: HR 3.2 (95% CI 1.4-7), 2.9 (1.4-6.2), 3.4 (1.6-7.5), for Hb <6, 6-8, and 8-10 g/dL compared to patients with Hb >10, respectivelyAs regards complications, infections were observed in 14% of cases, mostly mixed AIHA (p=0.02); thrombosis occurred in 10% and acute renal failure in 3% of patients, with no relationship with AIHA type/Hb values. Evans\u2019 syndrome was more frequent in mixed or atypical cases (p=0.04) and in severe forms (74% with Hb<8 g/dL vs 26%, p=0.005), and was associated with higher relapse risk (HR 2.3, 95% CI 1.4-3.9). Seventy patients died during the followup, and 12 because of AIHA-related acute complications. Higher mortality was observed for infections (HR 5.8, 95% CI), acute renal failure (HR 7.6, 95% CI) and Evans\u2019 syndrome (HR 8.3, 95% CI).Summary/Conclusions: In conclusion, we found that severity of anemia at onset was the major determinant of relapse risk. The lowest Hb levels were observed in patients with IgG+C WAIHA and atypical cases along with higher LDH levels and inadequate reticulocytosis, advising strict clinical observation in these patient