Upper and/or lower respiratory tract infection caused by human metapneumovirus after allogeneic hematopoietic stem cell transplantation.

peer reviewed[en] PATIENTS AND 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 allogeneic stem cell transplantation (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

New trends in the management of cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a survey of the Infectious Diseases Working Pary of EBMT

The management of cytomegalovirus (CMV) infection was assessed with a survey performed in 2020 by the Infectious Diseases Working Party of European Society for Blood and Marrow Transplantation (EBMT). One-hundred-eighty of the 579 EBMT centres (31%) responded. CMV monitoring with quantitative PCR for CMV-DNAemia was used by 97% of centres while the duration of monitoring was variable according to the patient immune recovery and the ongoing immunosuppressive therapy. CMV prophylaxis for high-risk patients was used in 101 (56%) of centres: letermovir in 62 centres (61%), aciclovir/valaciclovir in 19 centres (19%), ganciclovir/valganciclovir in 17 centres (17%), foscarnet in 3 (3%). The most used trigger for pre-emptive therapy was a threshold of >10(3) copies/ml or >10(3) IU/ml. Ganciclovir/valganciclovir confirmed the preferred first line treatment both for pre-emptive and CMV disease therapy. CMV-cytotoxic T-cells were used mainly in the setting of relapsing/refractory CMV disease. Forty-eight centres reported CMV refractory/resistant infection due to mutated CMV strain.This survey showed that letermovir prophylaxis is adopted by more than half of centres using a prophylaxis approach for CMV infection. How letermovir prophylaxis will modify other important pillars of daily CMV management, such as frequency of CMV-DNAemia monitoring and preemptive therapy, remain a matter of investigation

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

Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients:Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia &lt;500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.</p

Use of letermovir in off-label indications: Infectious Diseases Working Party of European Society of Blood and Marrow Transplantation retrospective study.

Letermovir (LMV) is licensed for prophylaxis of CMV infection in allogeneic hematopoietic cell transplant adult CMV-seropositive patients. Due to its favorable safety profile, LMV brings potential for use in other clinical situations, outside the approved indication. The objective of the study was to analyze the efficacy and safety of the use of LMV in off-label indications in EBMT centers. A total of 49 patients were reported including 44 adults and 5 children. LMV was administered for: secondary prophylaxis (37 adults, 3 children), primary prophylaxis (2 children), pre-emptive treatment (5 adults), and therapy of CMV disease (2 adults; pneumonia, colitis). Cyclosporine was concomitantly used in 26 patients. Overall, LMV was used for a median 112 days (range: 10-473). Cumulative incidence of breakthrough infections during secondary prophylaxis was 10.1% (95% CI = 3.1-21.9). Prophylactic treatment with LMV resulted in 94.9% (95% CI = 81.0-98.7), and 81.9% (95% CI = 65.7-90.9) probability of, respectively, 60 and 120-day survival without CMV infection in patients receiving secondary prophylaxis. During therapy of CMV infection/disease, probability of 60 and 120-day overall survival was 100% and 71.4% (95% CI = 25.8-92.0), respectively. No breakthrough infection occurred in children on LMV prophylaxis. Adverse events were reported in 15/49 (30.4%) patients: the most common being nausea/vomiting (22.4%). In conclusion, the efficacy of the use of LMV as secondary prophylaxis was high, and the preliminary experience with the use of LMV for the treatment of patients with refractory CMV infection/disease was positive. Our data showed that higher dose or prolonged therapy did not result in increased rate of adverse events

Thiotepa-busulfan-fludarabine (TBF) conditioning regimen in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis: an outcome analysis from the Chronic Malignancies Working Party of the EBMT

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option in MF. There is no consensus on the optimal conditioning regimen. We report outcomes of 187 patients with MF transplanted between 2010 and 2017 conditioned with TBF. Median age was 58 years. Median interval from diagnosis to allo-HCT was 44 months. Donors were haploidentical (41%), unrelated (36%) or HLA-identical siblings (23%). Stem cell source was PB in 60%. Conditioning was myeloablative in 48% of cases. Antithymocyte globulin (ATG) was used in 41% of patients. At 100 days, neutrophil and platelet engraftment were 91% and 63% after a median of 21 and 34 days, respectively. Grade II-IV and III-IV acute GVHD occurred in 24% and 12%, while at 3 years, all grade chronic GVHD and chronic extensive GVHD had been diagnosed in 38% and 11%. At 3 years, OS, RFS and GRFS were 55%, 49% and 43%, respectively. RI and NRM were 17% and 33%. On multivariate analysis, poor KPS and the use of unrelated donors were associated with worse GRFS and a higher grade II-IV acute GVHD, respectively. Neither donor type nor intensity of the conditioning regimen influenced survival outcomes. TBF is a feasible conditioning regimen in allo-HCT for MF in all donor settings although longer term outcomes are required

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 (&gt;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.</p

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 &lt; 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 &lt; 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