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Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality.

ABSTRACT: Viral respiratory infections (VRIs) contribute to the morbidity and transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and strategies to prevent and treat VRIs are warranted. We monitored VRIs before and after transplant in children undergoing allogeneic HSCT with nasopharyngeal aspirates (NPA) and assessed the impact on clinical outcome. Between 2007 and 2017, 585 children underwent 620 allogeneic HSCT procedures. Out of 75 patients with a positive NPA screen (12%), transplant was delayed in 25 cases (33%), while 53 children started conditioning with a VRI. Patients undergoing HSCT with a positive NPA screen had a significantly lower overall survival (54% vs. 79%) and increased TRM (26% vs. 7%) compared to patients with a negative NPA. Patients with a positive NPA who delayed transplant and cleared the virus before conditioning had improved overall survival (90%) and lower TRM (5%). Pre-HSCT positive NPA was the only significant risk factor for progression to a lower respiratory tract infection and was a major risk factor for TRM. Transplant delay, whenever feasible, in case of a positive NPA screen for VRIs can positively impact on survival of children undergoing HSCT.

SUBMITTER: Ottaviano G

PROVIDER: S-EPMC7161889 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality.

Ottaviano Giorgio G Lucchini Giovanna G Breuer Judith J Furtado-Silva Juliana M JM Lazareva Arina A Ciocarlie Oana O Elfeky Reem R Rao Kanchan K Amrolia Persis J PJ Veys Paul P Chiesa Robert R

British journal of haematology 20190930 4

Viral respiratory infections (VRIs) contribute to the morbidity and transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and strategies to prevent and treat VRIs are warranted. We monitored VRIs before and after transplant in children undergoing allogeneic HSCT with nasopharyngeal aspirates (NPA) and assessed the impact on clinical outcome. Between 2007 and 2017, 585 children underwent 620 allogeneic HSCT procedures. Out of 75 patients with a positi ...[more]

PMID: 31566733

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Project description:BACKGROUND:Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). RESULTS:This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients' follow-up: the early period (0-30?days after Allo-HSCT), the intermediate period (30-100?days after Allo-HSCT) and the late period (>?100?days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of <?1000?ng/ml (median 6d vs 8d, p?=?0.036). MBL levels <?1000?ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00-6.13), neutropenic period (0-30?days, RR 3.28, 95% CI 1.53-7.06) and intermediate period (30-100?days, RR 2.37, 95% CI 1.15-4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels <?1000?ng/ml (hazard ratio 5.55, 95% CI 1.17-26.30, p?=?0.03) but not with MBL2 genotype. CONCLUSIONS:Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6?months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.

Project description:Survival rates for pediatric cancer have steadily improved over time but it remains a significant cause of morbidity and mortality among children. Infections are a major complication of cancer and its treatment. Community acquired respiratory viral infections (CRV) in these patients increase morbidity, mortality and can lead to delay in chemotherapy. These are the result of infections with a heterogeneous group of viruses including RNA viruses, such as respiratory syncytial virus (RSV), influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (HMPV), rhinovirus (RhV), and coronavirus (CoV). These infections maintain a similar seasonal pattern to those of immunocompetent patients. Clinical manifestations vary significantly depending on the type of virus and the type and degree of immunosuppression, ranging from asymptomatic or mild disease to rapidly progressive fatal pneumonia Infections in this population are characterized by a high rate of progression from upper to lower respiratory tract infection and prolonged viral shedding. Use of corticosteroids and immunosuppressive therapy are risk factors for severe disease. The clinical course is often difficult to predict, and clinical signs are unreliable. Accurate prognostic viral and immune markers, which have become part of the standard of care for systemic viral infections, are currently lacking; and management of CRV infections remains controversial. Defining effective prophylactic and therapeutic strategies is challenging, especially considering, the spectrum of immunocompromised patients, the variety of respiratory viruses, and the presence of other opportunistic infections and medical problems. Prevention remains one of the most important strategies against these viruses. Early diagnosis, supportive care and antivirals at an early stage, when available and indicated, have proven beneficial. However, with the exception of neuraminidase inhibitors for influenza infection, there are no accepted treatments. In high-risk patients, pre-emptive treatment with antivirals for upper respiratory tract infection (URTI) to decrease progression to LRTI is a common strategy. In the future, viral load and immune markers may prove beneficial in predicting severe disease, supporting decision making and monitor treatment in this population.

Project description:BackgroundThe role of conditioning intensity and stem cell source on modifying pre-transplantation risk in allogeneic haematopoietic stem cell transplantation (HSCT) is a matter of debate, but crucial when benchmarking centres.MethodsThis Retrospective, multicenter exploratory-validation analysis of 9103 patients, (55.5% male, median age 50 years; 1-75 years range) with an allogeneic HSCT between 2010 and 2016 from a matched sibling (N = 8641; 95%) or matched unrelated donor (N = 462; 5%) for acute myeloid (N = 6432; 71%) or acute lymphoblastic (N = 2671; 29%) leukaemia in first complete remission, and reported by 240 centres in 30 countries to the benchmark database of the European Society for Blood and Marrow Transplantation (EBMT) searched for factors associated with use of transplant techniques (standard N = 6375;70% or reduced intensity conditioning N = 2728;30%, respectively bone marrow N = 1945;21% or peripheral blood N = 7158;79% as stem cell source), and their impact on outcome.FindingsTreatment groups differed significantly from baseline population (p < 0.001), and within groups regarding patient-, disease-, donor-, and centre-related pre-transplantation risk factors (p < 0.001); choice of technique did depend on pre-transplantation risk factors and centre (p < 0.001). Probability of overall survival at 5 years decreased systematically and significantly with increasing pre-transplantation risk score (score 2 vs 0/1 HR: 1·2, 95% c.i. [1·1-1·.3], p = 0.002; score 3 vs 0/1 HR: 1·5, 95% c.i. [1·3-1·7], p < 0.001; score 4/5/6 vs 0/1 HR: 1·9, 95% c.i. [1·6-2·2], p < 0.001) with no significant differences between treatment groups (likelihood ratio test on interaction: p = 0.40). Overall survival was significantly associated with selection steps and completeness of information (p < 0.001).InterpretationPatients' pre-transplantation risk factors determine survival, independent of transplant techniques. Transplant techniques should be regarded as centre policy, not stratification factor in benchmarking. Selection criteria and completeness of data bias outcome. Outcomes may be improved more effectively through better identifying pre-transplantation factors as opposed to refinement of transplant techniques.FundingThe study was funded by EBMT.

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Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality.

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Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality.

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