Probable invasive aspergillosis in adult patient after haematopoietic stem cell transplantation: a case report

Universitatea de Stat de Medicină din Belarus, Minsk, Belarus, Spitalul Clinic Municipal nr. 9, Minsk, BelarusRezumat Introducere. Infecţiile sunt, deocamdată, cauza principală de deces a pacienţilor adulţi, beneficiari de transplant de celule stem hematopoietice (TCSH). Morbiditatea și mortalitatea de aspergiloză pulmonară invazivă rămâne importantă în rândul recipienţilor TCHS. Un diagnostic de aspergiloză invazivă nu este ușor de confirmat, iar comunicările de caz clinic referitoare la acest tip de infecţie la pacienţii adulţi, beneficiari de TCSH, sunt rareori publicate. Prezentare de caz. Este descris cazul clinic al unui pacient cu limfom Hodgkin, care, probabil, a dezvoltat o formă de aspergiloză pulmonară invazivă după un transplant autolog de celule stem hematopoietice. Infecţia fungică a fost tratată sistemic cu antifungice, dar aceasta s-a dovedit a fi rezistentă la voriconazol, totodată a cedat la administrarea caspofunginei. Discuţii. Acest caz prezintă date clinice interesante și imagini referitoare la diagnosticul aspergilozei pulmonare și indică posibilităţile existente de tratament antifungic. Concluzii. Incidenţa înaltă a aspergilozei invazive la pacienţii beneficiari de TCSH trebuie luată în consideraţie de către medicii care se ocupă de pacienţii transplantaţi. Chiar dacă izolarea prin cultură nu este întotdeauna posibilă, alte semne clinice și teste de laborator (galactomannanul, tomografia computerizată, microscopia sputei) pot fi utile pentru stabilirea diagnosticului de aspergiloză. Voriconazolul rămâne tratamentul de primă linie la pacienţii cu aspergiloză invazivă, cu posibilitatea utilizării echinocandinelor, în cazuri refractare. Abstract Introduction. Infections still stay one the leading causes of death in adult patients undergoing HSCT. Invasive pulmonary aspergillosis remains an important cause of morbidity and mortality in HSCT recipients. Diagnosis of invasive aspergillosis is not easy to be proven, and clinical data regarding this infection in adult HSCT recipients are rarely published. Case presentation. In the present case report, we describe a patient with a Hodgkin’s lymphoma, who developed probable invasive pulmonary aspergillosis after tandem autologous HSCT. The fungal infection was treated by systemic antifungal therapy, but the patient was refractory to voriconazole, showing clinical efficacy on caspofungin. Discussion. This case presents interesting clinical data and images concerning aspergillosis diagnosis and shows the possibilities of antifungal treatment in patients with invasive pulmonary aspergillosis. Conclusion. High incidence of invasive aspergillosis in HSCT patients should be kept in mind of practical doctors dealing with transplant patients. Even though the culture isolation is not always possible, other clinical and laboratory tests (galactomannan, CT-scan, sputum microscopy) may be useful for diagnosis of aspergillosis. Voriconazole remains a treatment of choice for patients with invasive aspergillosis, with a possibility of using echinocandins in refractory cases

COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and &gt;80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis

Biodiversity screening of gut microbiome during the allogeneic hematopoietic stem cell transplantation: data from the real-life clinical practice

Biodiversity of a gut microbiome has been shown as an important predictor of transplant-related outcomes and infections in allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center real-life clinical study and implemented a routine gut microbiome diversity monitoring across the course of allogeneic HSCT. Twelve patients (with ALL, AML, CML, biphenotypic leukemia and aplastic anemia) were enrolled in a stool samples collection protocol before the start of HSCT and during a 30-day post-transplant period. We have shown the feasibility of a gut microbiome monitoring in a real-life clinical setting and have proven that the alpha-biodiversity of the microbiome is significantly reduced with HSCT in comparison with the individual patient baseline level (Xdc 72.93; p < 0.001; multivariate Dirichlet analysis), what may be related to the antibiotic use and conditioning regimen. Overall, the gut microbiome biodiversity monitoring may be clinically used in a real-life HSCT setting to identify the high-risk groups for developing bloodstream infections and transplant-related negative outcomes

Diagnostic value of sepsis biomarkers in hematopoietic stem cell transplant recipients in a condition of high prevalence of gram-negative pathogens

Objective/background: A decision about the need for antimicrobial therapy in a patient with febrile neutropenia after hematopoietic stem cell transplantation (HSCT) is often complicated because of the low frequency of culture isolation and reduced clinical manifestation of infection. Usefulness and choice of sepsis biomarkers to distinguish bloodstream infection (BSI) from other causes of febrile episode is still argued in HSCT recipients in modern epidemiological situations characterized by the emergence of highly resistant gram-negative microorganisms. In this study a comparative analysis of diagnostic values of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) was performed as sepsis biomarkers in adult patients after HSCT in a condition of high prevalence of gram-negative pathogens. Methods: A prospective observational clinical study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. The biomarkers (presepsin, PCT, and CRP) were assessed in a 4-hour period after the onset of febrile neutropenia episode in adult patients after HSCT. Microbiologically-confirmed BSI caused by a gram-negative pathogen was set as a primary outcome. Results: Clinical and laboratory data were analyzed in 52 neutropenic patients after HSCT aged 18–79 years. Out of the biomarkers assessed, the best diagnostic value was shown in presepsin (area under the curve [AUC]: 0.889, 95% confidence interval [CI]: 0.644–0.987, p < .0001) with 75% sensitivity and 100% specificity, then in PCT (AUC: 0.741, 95% CI: 0.573–0.869, p = .0037) with 62% sensitivity and 88% specificity. The optimal cut-off value for CRP was set as 165 mg/L, while it had an average diagnostic value (AUC: 0.707, 95% CI: 0.564–0.825, p = .0049) with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT. Conclusion: Presepsin may be recommended in adult patients with suspected gram-negative BSI after HSCT as a possible additional supplementary test with a cut-off value of 218 pg/mL. PCT is inferior to presepsin in terms of sensitivity and specificity, but still shows a good quality of diagnostic value with an optimal cut-off value of 1.5 ng/mL. CRP showed an average diagnostic value with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT in a condition of high prevalence of gram-negative pathogens. Keywords: Bloodstream infections, C-reactive protein, Hematopoietic stem cell transplantation, Presepsin, Procalcitoni

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible