Risk factors for Nocardia infection among allogeneic hematopoietic cell transplant recipients: A case-control study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

OBJECTIVES: Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence. METHODS: We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests. RESULTS: Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001). CONCLUSIONS: We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.

Upper and/or Lower Respiratory Tract Infection Caused by Human Metapneumovirus After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.

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.

Prevalence, management, and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HCT: survey of Infectious Diseases Working Party EBMT.

The aim of this study was to determine the current approach of EBV-driven post-transplant complications in context of monitoring, diagnosis, prevalence and treatment in EBMT transplant centers. Routine serology testing in patient and donor before HCT is performed in 95.5% centers. Pretransplant EBV-DNA is routinely tested in all patients in 32.7% centers. Monitoring for EBV infection is feasible in 98.2% centers: including 66.7% centers using standardized PCR. Post-HCT regular monitoring is performed in all patients in 80.5% centers. Anti-EBV prophylaxis with rituximab is used in 12.4% centers. Frequency of csEBV-DNA-emia was 7.4% (adults: 6.2%, children: 12.6%). The PCR threshold used to start preemptive treatment was differentiated among centers. Frequency of EBV-PTLD was 1.6% (adults: 1.3%; children: 3.5%). First-line therapy of EBV-driven complications was rituximab and reduction of immunosuppressive therapy. The rate of failure of first-line preemptive treatment was 12.0%. EBV-specific viral-specific T-lymphocytes were available in 46.0% centers. A number of new experimental therapies were given in 28 patients with resistant/refractory PTLD. In conclusion, the prevalence of EBV-DNA-emia and EBV-PTLD over the period 2020-2021 decreased in comparison to historical data. New trends (routine pretransplant screening for EBV-DNA, wider access to VST, new experimental therapies) are being observed in management of EBV infection after allo-HCT.

Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party.

Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.

Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.

We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.

Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry.

Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.

Outcome of SARS-CoV2 infection in hematopoietic stem cell transplant recipients for autoimmune diseases.

Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection. The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.

Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study.

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

Infection prevention practices among EBMT hematopoietic cell transplant centers: the EBMT Infectious Disease Working Party survey.

We aimed to describe the current status of infection prevention practices among EBMT centers. Questionnaires were distributed to all 553 EBMT transplant centers to capture clinical practices regarding antimicrobial prophylaxis, protective measures, isolation procedures and growth-factor support of patients undergoing hematopoietic cell transplantation. Responses from 127 centers in 32 countries were obtained. Most centers housed patients in single rooms (autologous-82%; allogeneic-98%), with high-efficiency particulate air (HEPA)-filters (autologous-73%; allogeneic-100%) and positive pressure (autologous-61%; allogeneic-88%). Pre-engraftment G-CSF was utilized by 77 and 31% of centers after autologous and allogeneic transplantation, respectively (P < 0.00001). Antibacterial prophylaxis was provided by 57 and 69% (P = 0.086) of centers and antifungal prophylaxis by 65 and 84% (P = 0.0008) of centers, to patients undergoing autologous and allogeneic transplantation, respectively. Yet, 16 and 3% of centers provided neither antibacterial nor antifungal prophylaxis to patients undergoing autologous and allogeneic transplantation, respectively. Considerable variation existed between centers and across countries in antimicrobial prophylaxis practices, medications employed and duration of preventive therapy. There were considerable discordances between guidelines and daily practices. JACIE accredited and non-accredited centers did not differ significantly in their antimicrobial prophylaxis practices. Whether these differences between transplant centers translated into differences in infectious morbidity, mortality and financial costs, warrants further research.

Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modeling.

Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR]=0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.

HEV infection in stem cell transplant recipients-retrospective study of EBMT Infectious Diseases Working Party.

HEV infection is an emerging cause of acute and chronic hepatitis in stem cell transplant (SCT) recipients. We performed a retrospective observational study among EBMT centers with the aim of describing characteristics, management and outcome of HEV after SCT. There were 34 cases of HEV infection from 12 centers in 6 countries, diagnosed in median 4.5 months after SCT; 20 of acute and 14 of chronic infection. Non-hepatic findings possibly associated with HEV infection were present in 9 (26%). Patients with chronic infection had more characteristics associated with severely immunocompromised status. Ribavirin was provided to 16 patients (47%; 40% with acute and 57% with chronic infection), in median for 75 days. Three (19%) patients discontinued it due to side effects. HEV-RNA clearance occurred in 29 patients (85%; 85% in acute and 86% in chronic infection). HEV was considered a cause of death in 3 (9%), with 2 cases with late diagnosis. Reduction of immunosuppression in those receiving it, and ribavirin treatment in those with chronic infection were associated with shorter time to HEV-RNA clearance. Policy on HEV testing varied between the centers. In conclusion, acute and chronic HEV hepatitis should be promptly diagnosed and managed in SCT recipients.

Nocardia Infections in Hematopoietic Cell Transplant Recipients: A Multicenter International Retrospective Study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population. METHODS: This retrospective international study reviewed nocardiosis episodes in HCT recipients (1/1/2000-31/12/2018; 135 transplant centers; 33 countries) and described their clinical, microbiological, radiological, and outcome characteristics. RESULTS: We identified 81 nocardiosis episodes in 74 allo- and 7 auto-HCT recipients. Nocardiosis occurred a median of 8 (IQR: 4-18) months post-HCT. The most frequently involved organs were lungs (70/81; 86%) and brain (30/81; 37%); 29 (36%) patients were afebrile; 46/81 (57%) had disseminated infections. The most common lung imaging findings were consolidations (33/68; 49%) or nodules (32/68; 47%); brain imaging findings were multiple brain abscesses (19/30; 63%). Ten of 30 (33%) patients with brain involvement lacked neurological symptoms. Fourteen of 48 (29%) patients were bacteremic. Nocardia farcinica was the most common among molecularly identified species (27%; 12/44). Highest susceptibility rates were reported to linezolid (45/45; 100%), amikacin (56/57; 98%), trimethoprim-sulfamethoxazole (57/63; 90%), and imipenem (49/57; 86%). One-year and last follow-up (IQR: 4-42.5 months) all-cause mortality were 40% (32/81) and 52% (42/81), respectively. In the multivariable analysis, underlying disease not in complete remission (HR: 2.81; 95% CI: 1.32-5.95) and prior bacterial infection (HR: 3.42; 95% CI: 1.62-7.22) were associated with higher 1-year all-cause mortality. CONCLUSIONS: Nocardiosis is a late post-HCT infection usually manifesting as a pulmonary disease with frequent dissemination, brain infection, and bacteremia. Brain imaging should be performed in HCT recipients with nocardiosis regardless of neurological symptoms. Overall mortality is high.

Efficacy, safety and feasibility of treatment of chronic HCV infection with directly acting agents in hematopoietic stem cell transplant recipients - Study of infectious diseases working party of EBMT.

OBJECTIVES: Limited data is available on HCV directly acting agents (DAAs) in haematopoietic stem cell transplant (HSCT) recipients. This study aimed at reporting the characteristics, treatment practices and treatment efficacy in HSCT recipients with chronic HCV. METHODS: Prospective observational study from EBMT Infectious Diseases Working Party (IDWP). Patients with chronic HCV infection were included. RESULTS: Between 12/2015 and 07/2018, 45 patients were included: male in 53%; median age 49 years (range, 8-75); acute leukaemia in 48.9%, lymphoma in 17.7%, non-malignant disorders in 22.3%; allogeneic HSCT in 84%; 77.8% no immunosuppressive treatment. Genotypes 1, 2, 3 and 4 were detected in 54.5%, 20.5%, 13.6% and 11.4%, respectively; advanced fibrosis in 40%, including cirrhosis in 11.4%. Overall, 37 (82.2%) patients received DAAs, at a median of 8.4 years after HSCT (16.2% within 6 months from HSCT). Sofosbuvir-based treatment was given to 62.2%. Thirty-five patients completed planned treatment course, with sustained virological response (SVR) of 89.1%, and 94.3% (33/35) in those who completed the treatment. Side effects possibly related to DAAs were reported in 5 (14%) and did not require treatment discontinuation. CONCLUSIONS: DAAs treatment was effective, safe and feasible in this cohort of mainly allogeneic HSCT recipients with mild/moderate liver damage.

Current attitude to deferral of cellular therapy or nontransplant chemotherapy due to SARS-CoV-2 asymptomatic infection: Survey of Infectious Diseases Working Party EBMT.

The objective of the study was to assess the current clinical practice and the attitude toward deferral of HCT/chemotherapy in patients with hematological diseases in cases of asymptomatic patients with a positive assay for SARS-CoV-2. In August 2021, we performed a survey among EBMT centers regarding their attitude toward deferral of HCT/chemotherapy in patients with a positive PCR result. Centers were willing to defer the planned cellular therapy for patients with asymptomatic SARS-CoV-2 infection without previous COVID-19 disease, and patients who became asymptomatic after a previous COVID19 disease but persistently shed the virus, respectively, in case of high-risk allo-HCT (90.2%/76.9%), low-risk allo-HCT for malignant diseases (88.2%/83.7%), allo-HCT for nonmalignant diseases (91.0%/91.0%), auto-HCT (88.0%/79.8%), and CAR-T therapy (83.1%/81.4%). The respective rates toward deferral of noncellular therapy patients was lower for both groups of patients, and varied with the primary diagnosis and anti-malignant treatment. There is a relatively high rate of willingness to defer treatment in asymptomatic patients being positive for SARS-CoV-2, planned for cellular therapy, regardless of previous history of vaccination or COVID-19. The same approach is presented for most of patients before noncellular therapy. Nevertheless, each patient should be considered individually weighting risks and benefits.

COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey.

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

Impact of early candidemia on the long-term outcome of allogeneic hematopoietic stem cell transplant in non-leukemic patients: an outcome analysis on behalf of IDWP-EBMT.

We assessed the incidence and outcome of early candidemia after hematopoietic stem cell transplant (HSCT). The analysis included all first HSCTs performed from 2000 to 2015 in adult and pediatric patients with a non-leukemic disease and recorded in the EBMT registry. Overall survival (OS), non-relapse mortality (NRM), and relapse mortality (RM) were evaluated. Candidemia was diagnosed in 420 of 49,852 patients at a median time of 17 days post HSCT (range 0-100), the cumulative incidence being 0.85%. In 65.5% of episodes, candidemia occurred by day 30 after HSCT. The mortality rate by day 7 was 6.2%, whereas 100-day NRM was higher (HR 3.47, p < 0.0001), and 100-day OS was lower (HR 3.22, p < 0.0001) than that of patients without candidemia. After a median follow-up of 4.3 years, 5-year OS, NRM, and RM for patients with and without candidemia were 50.5% vs. 60.8%, p < 0.0001, 28.2% vs.18.8%, p < 0.0001, and 25.3% vs. 27.2%, p = 0.4, respectively. In conclusion, in non-leukemic transplant patients, the occurrence of an early episode of candidemia is rare but it is still associated with a negative effect on the outcome.

Seasonal Human Coronavirus Respiratory Tract Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Little is known about characteristics of seasonal human coronaviruses (HCoVs) (NL63, 229E, OC43, and HKU1) after allogeneic stem cell transplantation (allo-HSCT). METHODS: This was a collaborative Spanish and European bone marrow transplantation retrospective multicenter study, which included allo-HSCT recipients (adults and children) with upper respiratory tract disease (URTD) and/or lower respiratory tract disease (LRTD) caused by seasonal HCoV diagnosed through multiplex polymerase chain reaction assays from January 2012 to January 2019. RESULTS: We included 402 allo-HSCT recipients who developed 449 HCoV URTD/LRTD episodes. Median age of recipients was 46 years (range, 0.3-73.8 years). HCoV episodes were diagnosed at a median of 222 days after transplantation. The most common HCoV subtype was OC43 (n = 170 [38%]). LRTD involvement occurred in 121 episodes (27%). HCoV infection frequently required hospitalization (18%), oxygen administration (13%), and intensive care unit (ICU) admission (3%). Three-month overall mortality after HCoV detection was 7% in the whole cohort and 16% in those with LRTD. We identified 3 conditions associated with higher mortality in recipients with LRTD: absolute lymphocyte count <0.1 × 109/mL, corticosteroid use, and ICU admission (hazard ratios: 10.8, 4.68, and 8.22, respectively; P < .01). CONCLUSIONS: Seasonal HCoV after allo-HSCT may involve LRTD in many instances, leading to a significant morbidity.