ABSTRACT
Background: Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate Antibody is currently approved in combination with 7 + 3 in low- and intermediate risk acute myeloid leukaemia (AML). These patients are candidate for consolidation with autologous stem cell transplantation (ASCT) particularly when MRD- is obtained. GO can improve the rate of MRD negativity. There are limited data on the effect of its addition on the mobilization of Hemopoietic Stem Cells (HSC). Aims: To assess the feasibility of mobilization of HSC after re-introduction into market of GO at 3mg/m2 in 2019. Methods: We retrospectively studied AML patients undergoing 3+7 + GO induction and Ara-C + Daunorubicine + GO, consolidation (doses are derived from label instructions and ALFA0701 study) and mobilization on day +20 using GCSF 10μg/kg. CD34+ were monitored, and patients were harvested when a threshold of 20 cells/μL was reached in peripheral blood. Results: In 2020 and 2021, also considering constrains caused by COVID-19 pandemics, we attempted mobilization in our 3 Italian centres of 14 patients with a diagnosis of CD33+ de novo-AML. The median age was 52 years (range 29-65 yrs.), 4 were males and 10 females;11 patients carried a mutation of NPM1 and all had a normal karyotype except one with t(10p12;11q14) (Table 1). All received 3+7+GO induction and achieved a CR. Therefore, we started consolidation (total ARA-C 8g/m2) + GO as inpatient. Ten patients (71%) reached the established threshold of 20 CD34+ /μL and were successfully harvested, while 4 patients (29%) failed mobilization. The median day of apheresis was D+26 from the start to chemotherapy (range 22- 39). The median number of circulating CD34+ cells on the day of collection was 35.9 cells/μL (range 20-2153 cells/μL). The median CD34+ harvested was 4.65 x 106/kg (range 1.8- 44.6 x 106/kg). In our cohort, 4 patients (28% of the entire cohort and 40% of the harvested patients) underwent ASCT, 3 achieved favourable engraftment, while in the last patient ASCT is ongoing. Several reasons prevented ASCT in the remaining 6 patients: 3 patients underwent allogeneic SCT (2 had positive MRD on harvested apheresis;1 was reclassified as high-risk ELN2017 due to RUNX1 mutation resulting from NGS panel), 2 refused ASCT and one suffered early relapse. Summary/Conclusion: In our patients, the addition of GO did not impair HSC mobilization and harvesting that was reached in about 71% of cases, similarly to the AML-10 trial of the EORTC and GIMEMA Leukemia Groups where 70% of patients were successfully harvested. Our data are particularly interesting because in the pivotal ALFA0701 study, only one patient underwent Autologous- SCT, but in the control arm. An important limit of our case-series is that only 4 patients were auto-transplanted, so we have scant data on engraftment. In particular, evaluating day to engraftment of platelets would be interesting, given the known increase of thrombocytopaenia in patients treated with GO. In conclusion, mobilization with GO is feasible and further studies are warranted to evaluate the effects of fractioned doses of GO on HSC mobilization and ASCT outcome;the ongoing trial GIMEMA AML1819 - EudraCT number 2019-003871-20 - will prospectively assess the effect of GO, but with lower doses of ARA-C (total ARA-C 6 g/m2). (Table Presented).
ABSTRACT
Aims: The SARS-CoV-2 infection is mostly characterized by acute lung injury. Yet, some COVID-19 patients showed also neurological signs, acute myocardial injury, heart failure, myocarditis, and hypercoagulability, such as pulmonary embolism. Cardiac biomarkers can play an essential role in the diagnosis, management, and prognosis of COVID-19. In fact, during hospitalization, these patients develop biochemical abnormalities, with increasing of all Troponins (TnT), B-type natriuretic peptide (NT-pro-BNP) and creatine kinase-myocardial band (CK-MB) levels. This situation helps us to predict adverse outcomes, especially in patients with cardiovascular comorbidities or risk factors. Data emerged demonstrated a myocardial involvement which determines a high risk of adverse events and increasing of mortality. Methods and results: Lots of meta-analysis emphasize that a great number of hospitalized patients with moderate and severe forms of COVID-19 developed acute myocardial damage, defined as an increase of cardiac biomarkers, such NT-pro-BNP, CK-MB, and of all type of troponins. The highest mortality rate is related with progressively increasing biomarkers levels and with a history of cardiovascular disease. In fact, the biomarkers dosage should be considered as a prognostic marker in all patients with COVID-19 disease at admission, during hospitalization and in the case of clinical deterioration. Our purpose is to evaluate cardiovascular prognostic factors in COVID-19 disease throughout the analysis of cardiac biomarkers to early identify the most serious patients and to optimize their outcomes. Results of aforementioned studies underline how cardiac biomarkers are associated with severe form of COVID- 19 infection. Above all, higher levels of these biomarkers are significantly associated with an increased risk of the mortality in COVID-19 infected patients. Therefore, has been demonstrated COVID-19 infection is more severe in those patients with a previous history of arterial hypertension, cardiovascular diseases. In addition to classical laboratory parameters evaluated in COVID-19 infection, such as C Reactive Protein (CRP), D-dimer, and lactate dehydrogenase (LDH), which are currently used in clinical practice, others biomarkers could potentially be useful for screening, clinical management, and prevention of serious complications. Therefore, it is clinically significant that fluctuating levels of myocardial biomarkers are closely monitored and patients with high levels of myocardial biomarkers are treated promptly to improve prognosis. At the end, on basis of symptoms and cardiac biomarkers patients could be divided in mild, severe and critical. Conclusions: Biomarkers of acute myocardial injury play an important role in predicting worsening prognosis for COVID-19 patients with and without myocardial injury. They are not only predictive of disease severity, but are also helpful for therapeutic management, based on drugs preventing the activation of coagulation processes. It's important, above all, to identify a laboratory score, made by haematological, inflammatory, biochemical, and immunological parameters, may help to stratify COVID-19 positive patients into risk categories for deciding therapeutic management, thus avoiding cardiac compromise which, as we have previously analysed, is an indication of a poor prognosis.
ABSTRACT
Background. During the lockdown period in Italy, from March 11th to May 4th 2020, a progressive increase in COVID-19 cases occurred in all Italian regions, in particular in the Lombardy Region. The current rise in COVID-19 cases has led to an increasing involvement of hospitals, in order to face the Coronavirus outbreak, shifting healthcare resources towards the management of COVID+ patients. This has led, on the other hand, to a progressive decrease in hospital admissions due to conditions not associated with SARS-CoV2 infection. During COVID-19 outbreak period, it has been observed a decrease in hospital admissions for acute myocardial infarction. This phenomenon put in serious difficulty the clinical management of COVID-free patients with cardiovascular disease, at the beginning of phase 2 (starting from May 4 2020). Purpose. In this scenario, we aimed to verify the impact of telemedicine during lockdown, in comparison with the same period in 2019. Materials and method. We analyzed 12-lead ECGs recorded by 5000 country pharmacies, evaluated and stored in one telemedicine platform provided by Health Telematic Network (HTN), in cooperation with our Cardiology Department, Federfarma (Pharmacists' National Association), and Italian National Health Institute. Results. During the lockdown period, were recorded 6,104 ECGs in territorial pharmacies, compared to 17,280 ECGs done in the same period in 2019. Chest pain symptom represented the cause of recording ECG in 298 patients (4.88%) during the lockdown period, compared to 402 patients (2.33%) in the same period in 2019, with an increase of 109.86%. In the Lombardy Region, during lockdown period, were reported 118 accesses to territorial pharmacies for chest pain (about 39.50% of total cases in Italy). Among these, 36 accesses were in the province of Brescia (about 30.50%), whereas 28 of them were in the province of Bergamo (about 23.73%). Among ECGs performed, 8 showed typical abnormalities of acute myocardial infarction with ST elevation (STEMI, 2.68%) in the lockdown period, compared to 7 STEMIs (1.74%) detected in the same period in 2019, with an increase of 54.17%. These patients were referred to Emergency Department (ED) suddenly, for the therapeutic intervention. Conclusion. These data shown that a large number of patients with cardiovascular symptoms preferred to go to territorial pharmacies rather than hospitals during the COVID outbreak period. Telemedicine played a prominent role in managing patients with cardiovascular symptoms at home. Moreover, this service allowed patients with STEMI to access to the hospitals faster, avoiding the risks of a serious diagnostic delay. Furthermore, by analyzing the data of Lombardy Region, it was possible to show how a significant component of access to local pharmacies for chest pain occurred in the region most affected by the COVID-19 outbreak.
ABSTRACT
Background. During the lockdown period in Italy, from March 11th to May 4th 2020, a progressive increase in COVID-19 cases occurred in all Italian regions, in particular in the Lombardy Region. The current rise in COVID-19 cases has led to an increasing involvement of hospitals, in order to face the Coronavirus outbreak, shifting healthcare resources towards the management of COVID+ patients. This has led, on the other hand, to a progressive decrease in hospital admissions due to conditions not associated with SARS-CoV2 infection. At the same time, the regional governments have provided for the suspension of all outpatient activities, with the exception of the non-deferrable one. It was decided to postpone any elective intervention, referring to COVID free hospitals any urgent or emergency intervention. Purpose. We aimed to verify the impact of coronavirus outbreak in the management of patients with high risk of morbidity and mortality, followed at the Cardiology Outpatient Clinic of our hospital, that was a Hub center for COVID patients. Materials and method. We compared the total number of Day Hospital (DH) visits for worsening heart failure (WHF), severe aortic stenosis waiting for Transcatheter Aortic Valve Implantation (TAVI) and atrial fibrillation (AF) requiring electrical cardioversion (ECV) between March 4th and May 4th of 2019 with those that refer to the same period in 2020. Then, we evaluated the same data in the 30 days following the end of the lockdown (May-June 2020). Results. As reported in Figure 1, the number of DH visits during March-May 2019 was approximately double compared to the ones in the same interval time in 2020 (81 vs 34 patients). Instead, in just one month (18/05-18/06/2020) there was a significant increase in the number of accesses for WHF (globally 22), if compared with those (21 in total) during the entire lockdown (lasting three months, from 04/03 to 04/05/2020). Figure 1. Number of MAC accesses in the indicated periods. C = heart failure;T = TAVI;F = atrial fibrillation. March-May 2019 March-May 2020 May-June 2020 Conclusion. These data confirm how the COVID outbreak impacted negatively on the appropriate management and timing of therapeutic intervention for severe cardiovascular disease, in particular those with high risk of events and mortality, especially in the regions with highest number of hospitalizations and deaths for SARS-CoV-2.