Current antimicrobial practice in febrile neutropenia across Europe and Asia: the EBMT Infectious Disease Working Party survey

The aim of this survey was to summarize the current antimicrobial practice in febrile neutropenia and the presence of key aspects of antimicrobial stewardship. A questionnaire was sent to 567 centers, and complete responses were obtained from 194 (34.2%). Fluoroquinolone and co-trimoxazole prophylaxis are used in 57.1% and 89.1%, respectively. In 66.4%, the first-line empirical therapy is piperacillin/tazobactam, whereas 10.9% use carbapenems. Empirical combination therapy is used in stable patients without history of resistant pathogens in 37.4%. De-escalation to monotherapy is performed within 3 days in 35.3% and after 10 days in 19.1%. Empirical addition of a glycopeptide is performed when fever persists more than 2\u20133 days in 60.8%. Empirical escalation to a broader spectrum agent is performed when fever persists more than 3\u20135 days in 71.4%. In case of positive blood cultures with a susceptible pathogen and uncomplicated presentation, 76.7% of centers de-escalate and 36.6% discontinue before neutrophil recovery. In fever of unknown origin with uncomplicated presentation, 54.1% of centers de-escalate and 49.5% discontinue before neutrophil recovery. Recommendations put forward in the ECIL guidelines are not widely implemented in clinical practice. Specific problems include overuse of carbapenems and combination therapy and unjustified addition of glycopeptides without further de-escalation or discontinuation

No report on Zika virus infection in EBMT registry: Infectious Diseases Working Party statement

reserved7mixedStyczynski, J.; Hoek, J.; Knelange, N.; Mikulska, M.; Cesaro, S.; Aljurf, M.; Gil, L.Styczynski, J.; Hoek, J.; Knelange, N.; Mikulska, M.; Cesaro, S.; Aljurf, M.; Gil, L

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

The prognostic impact of the cytomegalovirus serostatus in patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a report from the Infectious Diseases Working Party of EBMT

It has been shown recently that donor and/or recipient cytomegalovirus (CMV) seropositivity is associated with a significant overall survival (OS) decline in acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We now analyzed the prognostic impact of the donor/recipient CMV serostatus in 6968 patients with chronic hematological malignancies who underwent allo-HSCT. Donor and/or recipient CMV seropositivity was associated with a significantly reduced 2-year progression-free survival (PFS, 50% vs. 52%, p = 0.03) and OS (62% vs. 65%, p = 0.01). Multivariate Cox regression analyses showed an independent negative prognostic impact of donor and/or recipient CMV seropositivity on PFS (HR, 1.1; 95% CI, 1.0\u20131.2; p = 0.03), OS (HR, 1.1; 95% CI, 1.0\u20131.2; p = 0.003), and non-relapse mortality (HR, 1.2; 95% CI, 1.0\u20131.3; p = 0.02). OS decline was strongest for CMV-seropositive recipients with a CMV-seronegative donor (HR, 1.2; 95% CI, 1.1\u20131.3), followed by CMV-seropositive patients with a CMV-seropositive donor (HR, 1.1; 95% CI, 1.0\u20131.2). Conversely, OS did not differ significantly between CMV-seronegative recipients allografted from a CMV-seropositive donor (HR, 1.0; 95% CI, 0.9\u20131.2) and patients with donor/recipient CMV seronegativity (p = 0.001 for the four groups together). Non-relapse mortality was also significantly (p = 0.01) higher for CMV-seropositive patients with a CMV-seronegative graft (HR, 1.2; 95% CI, 1.1\u20131.4) than for CMV-seropositive patients with a CMV-seropositive graft (HR, 1.1; 95% CI, 0.9\u20131.2) or CMV-seronegative recipients with a CMV-seropositive graft (HR, 1.0; 95% CI, 0.8\u20131.2). Donor and/or recipient CMV seropositivity still results in an OS decline in patients with chronic hematological malignancies who have undergone allo-HSCT. However, this OS decline seems to be lower than that described for acute leukemia patients previously

Prognostic impact of EBV serostatus in patients with lymphomas or chronic malignancies undergoing allogeneic HCT

The influence of the donor (D) and recipient (R) pre-transplant Epstein-Barr Virus (EBV) serostatus on transplant outcomes (overall survival, relapse-free survival, relapse incidence, non-relapse mortality, acute and chronic GVHD) in 12,931 patients with lymphomas or chronic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) between 1997- 2016 was analyzed. In multivariate analysis, the risk of development of chronic GVHD was increased for EBV R+/ D+ (HR = 1.26; p = 0.003), R+/D- (HR = 1.21; p = 0.044), and R-/D + (HR = 1.21; p = 0.048) in comparison to R-/D- transplants. No significance was shown for other transplant outcomes; however, in univariate analysis, EBV-seropositive patients receiving grafts from EBV-seropositive donors (EBV R+/D+ transplants) had inferior transplant outcomes in comparison to EBV-seronegative recipients of grafts from EBV-seronegative donors (EBV R-/D-): inferior overall survival ( 59.6% vs 65.9%), inferior relapse-free survival (51.1% vs 57.5%), increased incidence of chronic GVHD (49.5% vs 41.8%), and increased incidence of de novo chronic GVHD (30.5% vs 24.0%). In conclusion, an EBV-negative recipient with lymphoma or chronic malignancy can benefit from selection of an EBV-negative donor in context of chronic GVHD, while there are no preferences in donor EBV serostatus for EBV-seropositive recipient.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Nocardia infections in hematopoietic cell transplant recipients: a multicenter international retrospective study of the Infectious Diseases Working Party (IDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

peer reviewedBACKGROUND: Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population. METHODS: In this retrospective international study, we reviewed nocardiosis episodes in HCT recipients (01.01.2000-31.12.2018; 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 at 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%); and brain imaging findings were multiple brain abscesses (19/30; 63%). 10/30 (33%) patients with brain involvement lacked neurological symptoms. 14/48 (29%) patients were bacteremic. N. 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 one-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

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

Primary Plasma Cell Leukaemia (pPCL) is a rare and challenging malignancy. There is limited data regarding optimum transplant approaches. Therefore we undertook a retrospective analysis from 1998-2014 of 751 patients with Primary Plasma Cell Leukaemia (pPCL) undergoing one of four transplant strategies; single autologous transplant (single-auto), single allogeneic transplant (allo-first) or a combined tandem transplant either auto-allo or 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 subsequent administration of second transplant. The allo-first group had lower relapse rate (45.9%, 95%CI 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher NRM (27%, 95%CI 15.9-38.1 vs 7.3%, 5.2-9.4) at 36 months. Allo-first had remarkably higher risk in the first 100 days for both OS and PFS. Autoallo (n=122) had no increased risk in the short term and significant benefit in PFS post-100 days compared to single auto (HR 0.69, 95%CI: 0.52-0.92, p=0.012). Auto-auto (n=117) was an effective option for patients achieving CR prior to first transplant, whereas in patients without CR prior to transplant our modelling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplant in pPCL to date. We confirm 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 guide clinical decisions on transplant strategy

Nocardia infections in hematopoietic cell transplant recipients: a multicenter international retrospective study of the Infectious Diseases Working Party (IDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

BACKGROUND: Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population. METHODS: In this retrospective international study, we reviewed nocardiosis episodes in HCT recipients (01.01.2000-31.12.2018; 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 at 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%); and brain imaging findings were multiple brain abscesses (19/30; 63%). 10/30 (33%) patients with brain involvement lacked neurological symptoms. 14/48 (29%) patients were bacteremic. N. 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 one-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