Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter crosssectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs Krzysztof Czyżewski and Jan Styczyński contributed equally to this work.
No epidemiological data exist so far on invasive mucormycosis (IM) in Polish hematopoietic cell transplantation (HCT) and pediatric hemato-oncology (PHO) centers. The objective of this study was to analyze the incidence, clinical course, therapy, and outcome of IM in pediatric and adult patients undergoing HCT and children with hemato-oncological diseases in Poland. A total number of 12425 at-risk patients were retrospectively analyzed, and the period between 2010 and 2019 was included. Patients were analyzed in three groups: nontransplant children with malignancies, children undergoing HCT, and adults after HCT. Twenty-one patients were diagnosed with IM, including 15 children (10 non-HCT, 5 HCT) and 6 HCT adults. Proven IM was confirmed in 18 patients, probable in 2 patients, and possible in 1 patient. Proven IM was diagnosed in 7.1% of all patients with invasive fungal diseases (IFDs), including 8.1% among PHO patients, 5.4% among pediatric HCT patients, and 7.0% among adult HCT patients. Clinically, pneumonia was diagnosed in 10 (47.6%) patients, involvement of the paranasal sinuses was found in 3 (14.3%) patients, gastrointestinal disease was noted in 2 (9.5%) patients, and disseminated mucormycosis was found in 6 (28.6%) patients. The probability of overall survival in IM patients was 0.50 ± 0.11. Infection-related mortality (IRM) was 10% for pediatric nontransplant IM patients and 82% for transplant IM (pediatric + adult) patients (p = 0.004). Among the transplant patients, all adults died within 120 days. IRM for pediatric HCT patients was 60% (p = 0.038). The only prognostic factor was HCT, which adversely influenced survival in IM patients.
The recommended pharmacological therapy for patients with coronary artery disease (CAD) treated by coronary artery bypass grafting (CABG) is acetylsalicylic acid (ASA). To improve the antiplatelet effect, supplementation with flavonoids is also recommended. The aim of this study was to estimate anti-aggregation properties of diosmin, in combination with ASA, pre- and postoperatively and assess the relationship of this therapy with inflammatory processes in CAD patients undergoing CABG. The study patients (n = 26) took diosmin (1000 mg/day); the control patients (n = 27) took a placebo. The therapeutic period for taking diosmin was from at least 30 days before to 30 days after CABG. All patients also took 75 mg/day ASA. Platelet aggregation and IL-6, CRP, and fibrinogen concentrations were determined before and 30 days after surgery. Results showed that diosmin did not enhance the anti-aggregation effect of ASA at any assessment time. However, there was a stronger anti-aggregation effect 30 days after surgery that was diosmin independent and was associated with acute-phase markers in the postoperative period. Increased levels of inflammatory markers in the late phase of the postoperative period may provide an unfavorable prognostic factor in long-term follow-up, which should prompt the use of stronger antiplatelet therapy in patients after CABG.
Background: Therapy-related acute myeloid leukemia (t-AML) represents emerging challenge of the modern oncology as a life-threatening complication of cytotoxic therapy. Disease characterises poor prognosis and presence of adverse cytogenetic and genetic abnormalities. The goal of the study: Clinical outcome of t-AML patients with respect to genetic changes and treatment intensity. Patients and methods: Retrospective analysis of all consecutive AML patients treated in years 2000-2021 in one hematological center was performed. Diagnosis of t-AML was established according to WHO 2016 criteria. Overall survival (OS) and progression free survival (PFS) was defined to evaluate treatment outcomes only within t-AML patients undergoing intensive treatment (standard induction/consolidation; allogeneic cell transplantation (alloHCT) if eligible). Results: Among 743 AML patients 60 (8.1%) were diagnosed as t-AML (38 woman) with median age 57 years. Solid tumors (ST) preceded t-AML in 63.3%, hematological neoplasms (HN) in 36.7%. Majority of t-AML was preceded by breast cancer (30.0%), Hodgkin Lymphoma (11.7%), non-Hodgkin Lymphoma (10.0%) and ovarian cancer (10.0%). Median latency time for ST and HN subgroups was 5 vs 7 years respectively (P = .036). Previous cytotoxic therapy consisted of chemotherapy, radiotherapy or combination in 56.6%, 18.3% and 25.0% (autologous cell transplantation was performed in 54.5% of HN). Cytogenetic and molecular biology analysis was performed in 44 and 27 of t-AML respectively. Cytogenetic abnormalities, complex karyotype and normal karyotype occurred in 78.9%, 28.9% and 15.8% patients. KMT2A, RUNX1-RUNX1T1 and PML-RARA rearrangement was found in 21.1%, 18.4% and 7.9% of t-AML. FLT3-ITD, FLT-TKD, NPM1 and C-KIT DNA sequence variant occurred as follows: 14.8%, 7.4%, 3.7% and 3.7% correspondingly. Three pathogenic TP53 DNA sequence variants were detected in t-AML patients: c.711G>A, c.704A>G and c.989T>C (analysis performed on 20 t-AML patients). According ELN2017 genetic risk stratification patients were classified as adverse, intermediate and favorable in 51.4%, 35.1% and 13.5% respectively. Intensive treatment was implemented in 48 patients including alloHCT in 23 of them. Median OS and PFS was 15 and 8 months respectively for whole treated group. Median OS in t-AML undergoing intensive chemotherapy only vs alloHCT was 7 vs 47 months (P = .0025) with 12-year OS after alloHCT- 21.1% (Fig.1A). Among therapy-related acute promyelocytic leukemia (t-APL) patients median OS was not reached, without alloHCT. Median OS was higher for t-AML patients younger than 65 years than older ones: 20 vs 13 months respectively (P = .048) (Fig.1B). Among t-AML median OS in subgroup with adverse ELN 2017 vs intermediate and favorable ELN 2017 was 15 vs 40 months (P = .037) with 5-years OS 8.2% vs 41.0% (Fig.1C). In multivariate Cox proportional hazard regression model alloHCT was the only factor significantly influencing OS (HR = 0.16, 95% CI = 0.05-0.56, P = .004). All patients with TP53 mutations were intensively treated, one patient underwent alloHCT. 66.6% of patients had complex karyotype and any co-occuring DNA sequence variant was detected. Importantly, c.704A>G and c.989T>C TP53 DNA sequence variants were not previously described in AML according Catalogue of Somatic Mutations In Cancer database. Median OS in t-AML with TP53 mutation vs without was 4 vs 7 months (P = .398) (Fig.1D). Conslusions: Our study brings detailed analysis of clinical outcome of t-AML. Patients with t-AML undergoing intensive treatment, younger than 65 years and with t-APL have significantly higher OS rates. On the contrary t-AML patients classified as adverse genetic ELN2017 subgroup have poorer OS rates. Treatment strategy in t-AML should rely on performing alloHCT possibly soon. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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