Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center.

Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were Fusarium spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by Scedosporium spp. (respectively 14.5% and 26.1%) and Alternaria spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for Fusarium spp., Scedosporium spp. or multiple pathogens IMD compared with Alternaria or other pathogens (51.7% vs. 17.6%, p < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, p = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.

OBJECTIVES: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. METHODS: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >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 hematological malignancy. RESULTS: The study included data from 3,603 elderly patients (aged 65 or older) with hematological 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. The 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 leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. CONCLUSION: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Improving Diagnosis of Pulmonary Mucormycosis: Leads From a Contemporary National Study of 114 Cases.

BACKGROUND: Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality. RESEARCH QUESTION: Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition? STUDY DESIGN AND METHODS: All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally. RESULTS: A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01). INTERPRETATION: Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL.

Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry.

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.

Invasive Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited.

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.

B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA).

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

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.

Frostbite and Cold Agglutinin Disease: Coexistence of Two Entities Leading to Poor Clinical Outcomes.

An 83-year-old woman was admitted to the emergency department for a 7-day history of fatigue and progressive cyanosis in the feet and hands after cold exposure despite physical protective measures. Upon arrival, the patient presented with necrotic cutaneous lesions in both hands and distal lower extremities. Upon admission, hemoglobin was 7.6 g/dL and laboratory tests were consistent with cold agglutinin disease (CAD), the presence of monoclonal IgM, and flow cytometry consistent with lymphoplasmacytic lymphoma, but MYD88 L265P mutation was negative. The patient required blood transfusion, resulting in stabilized hemoglobin and a decrease in markers of hemolysis. Treatment with aspirin 250 mg daily and intravenous iloprost 0.5 mL/h was initiated with a poor clinical response at day 4. Amputation was required. Plasma exchange was performed and chemotherapy with rituximab and bendamustine was initiated. The clinical course was marked by further necrosis, prompting discussions regarding an additional amputation that was not performed considering the high surgical risk and refusal by the patient. Supportive treatment was initiated, and the patient expired one month after hospital admission.

Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial.

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m2 of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1, and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.

Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study.

OBJECTIVES: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. PATIENTS AND METHODS: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. RESULTS: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01). CONCLUSIONS: Coinfections are frequent in IA patients and are associated with higher mortality.

Invasive Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) remains difficult to diagnose and to treat. Most common risk factors are prolonged neutropenia, hematopoietic stem cell or solid organ transplantation, inherited or acquired immunodeficiency, administration of steroids or other immunosuppressive agents including monoclonal antibodies and new small molecules used for cancer therapy. Critically ill patients are also at high risk of IPA. Clinical signs are unspecific. Early computed tomography (CT)-scan identifies the two main aspects, angioinvasive and airway invasive aspergillosis. Although CT-scan findings are not fully specific they usually allow early initiation of therapy before mycological confirmation of the diagnosis. Role of 18F-fludeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is discussed. Confirmation is based on microscopy and culture of respiratory samples, histopathology in case of biopsy, and importantly by detection of Aspergillus galactomannan using an immunoassay in serum and bronchoalveolar lavage fluid. Deoxyribonucleic acid detection by polymerase chain reaction is now standardized and increases the diagnosis yield. Two point of care tests detecting an Aspergillus glycoprotein using a lateral flow assay are also available. Mycological results allow classification into proven (irrespective of underlying condition), probable or possible (for cancer and severely immunosuppressed patients) or putative (for critically ill patients) IPA. New antifungal agents have been developed over the last 2 decades: new azoles (voriconazole, posaconazole, isavuconazole), lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex), echinocandins (caspofungin, micafungin, anidulafungin). Results of main trials assessing these agents in monotherapy or in combination are presented as well as the recommendations for their use according to international guidelines. New agents are under development.

Antifungal Therapy: New and Evolving Therapies.

Invasive fungal diseases primarily occur in immunocompromised patients. Immunosuppression has become more prevalent due to novel treatments, and this has led to a rise in the incidence of invasive fungal diseases. The antifungal armamentarium has long been insufficient and has taken quite some time to become diverse. Antifungal spectrum, tolerability, and toxicity are critical issues. Amphotericin B and its lipid formulations still have the widest spectrum, but, in spite of the better tolerance of the lipid formulations, toxicity remains a drawback, mostly with regard to renal function. Azoles constitute a heterogeneous antifungal class, in which newer molecules have an improved spectrum of activity. The main concern for the clinician when using azoles relates to the management of their many potential drug-drug interactions in an often fragile patient population. Echinocandins are better tolerated but possess a narrower antifungal spectrum and lack an oral route of administration. Still, their fungicidal activity makes them a weapon of first choice against Candida species. For certain uncommon fungal infections, antifungals such as flucytosine and terbinafine can also be useful. This article will give an overview of the mechanisms of action of currently used antifungals, as well as their spectrum of activity, clinically relevant pharmacological features, drug-drug interactions, and frequent side effects, all of which should drive the clinician's choice of agent when managing invasive fungal infections.

Allogeneic Stem Cell Transplantation in Therapy-Related Myelodysplasia after Autologous Transplantation for Lymphoma: A Retrospective Study of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy.

Therapy-related myelodysplastic syndrome (t-MDS) after autologous stem cell transplantation (ASCT) is a rare complication with no curative option. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for eligible patients and has been understudied in t-MDS. We report 47 consecutive patients with t-MDS after an ASCT who underwent allo-HSCT with a median age of 58 years (range, 30 to 71 years) at transplantation and a median follow-up of 22 months (range, 0.7 to 107). The median overall survival (OS) was 6.9 months (95% confidence interval [CI], 0 to 19 months). OS rates were 45% (29% to 60%) and 30% (15% to 45%) at 1 and 3 years after transplantation, respectively. On univariate analysis, prior therapy for t-MDS before allo-HSCT (P = .02) and mismatched donors (P = .004) were associated with poor OS. Three-year nonrelapse mortality (NRM) and relapse rates were 44% (25% to 63%) and 41% (22% to 61%), respectively. Mismatched donors (P < .001) were associated with higher NRM and a high-risk MDS (P = .008) with a higher relapse risk. On multivariate analysis, HLA mismatch was associated with higher NRM (hazard ratio, 6.21; 95% CI, 1.63 to 23.62; P = .007). In conclusion, our results suggest that one third of the patients who develop t-MDS after an ASCT for lymphoma are cured after an allo-HSCT. The use of mismatched donors with standard graft-versus-host disease prophylaxis should be avoided in such an indication for allo-HSCT. It will be worthwhile to see if the implementation of cyclophosphamide post-transplantation will improve the outcome with mismatched donors.