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New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study
Ricard, N., Zebali, L., Renard, C., Goutagny, M. P., Benezech, S., Bertrand, Y., Philippe, M., Domenech, C.
Cancers. 2023;15(7)
Abstract
BACKGROUND Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. METHODS We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. RESULTS 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. CONCLUSIONS IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.
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Teenagers and young adults with a past of allogenic hematopoietic stem cell transplantation are at significant risk of chronic kidney disease
da Silva Selistre, L., Renard, C., Bacchetta, J., Goutagny, M. P., Hu, J., Carla de Souza, V., Bertrand, Y., Dubourg, L., Domenech, C.
Pediatric nephrology (Berlin, Germany). 2021
Abstract
BACKGROUND Allogenic hematopoietic stem cell transplantation (aHSCT) remains the treatment of choice for some malignant hemopathies in children, albeit with the risk of long-term consequences, including chronic kidney disease (CKD). METHODS In our single tertiary referral center, we retrospectively assessed the long-term renal outcome in a cohort of children and adolescents who had undergone aHSCT for malignant hemopathies between 2003 and 2017. We distinguished glomerular and tubular dysfunctions and assessed the accuracy of the most common formula(s) to estimate glomerular filtration rate (GFR) during standard clinical follow-up. RESULTS Among the 166 patients who had received aHSCT, 61 underwent kidney functional assessment 1 to 10 years post-transplantation. Twenty-seven patients (44.3%) had a CKD with glomerular impairment, including 20 patients with a GFR?90 mL/min/1.73 m(2), and among these, 5 patients?60 mL/min/1.73 m(2). Patients with tubular signs had a significantly higher baseline GFR: 112 mL/min/1.73 m(2) [100; 120] versus 102 [99.0; 112.5] for patients without kidney involvement, and 76 [61; 86] for patients with CKD (p?0.01). Schwartz, CKiDU25, and EKFC formulas significantly overestimated mGFR, with a P30%?=?30%, which could lead to overlooking CKD diagnosis in this population. No patient reached kidney failure. CONCLUSIONS In conclusion, our study shows that CKD represents an important long-term sequela for children and adolescents who undergo aHSCT for malignant hemopathies, either with glomerular dysfunction or with the more insidious tubular dysfunction which could potentially impact growth. These patients could benefit from specialized long-term nephrology follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
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3.
Impact of a change in protected environment on the occurrence of severe bacterial and fungal infections in children undergoing hematopoietic stem cell transplantation
Libbrecht, C., Goutagny, M. P., Bacchetta, J., Ploton, C., Bienvenu, A. L., Bleyzac, N., Mialou, V., Bertrand, Y., Domenech, C.
European Journal of Haematology. 2016;97(1):70-7
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a procedure with a high infection risk. Strict isolation of patients is the rule to prevent such condition. OBJECTIVE We compared the occurrence of severe infections (bacteremia and invasive fungal infection, IFI) in children undergoing alloHSCT before and after the move to a new protected unit with decreases in isolation methods. METHODS The study was conducted over a 10-year period. Unit 1 (2002-2007) consisted of laminar airflow rooms where caregivers were required to wear a sterile outfit (gown, gloves, hat, and mask). Unit 2 (2008-2012) included spacious positive air pressure rooms with HEPA filters where only a clean gown and mask were required to be worn. RESULTS Two hundred eighty-six alloHSCTs were performed (144 in Unit 1 and 142 in Unit 2). We reported a total incidence of 4.78 infections/1000 hospital-days including 4.4 episodes of bacteremia and 0.38 episodes of IFI. There was no statistical difference in the incidence of infections: n = 4.98/1000 hospital-days in Unit 1 vs. n = 4.6/1000 in Unit 2 (P = 0.63). CONCLUSION The lack of difference in the occurrence of severe infection supports our decision to decrease unnecessary high protection in alloHSCT units to improve children's daily life. Copyright © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis
Bleyzac, N., Cuzzubbo, D., Renard, C., Garnier, N., Dubois, V., Domenech, C., Goutagny, M. P., Plesa, A., Grardel, N., Goutelle, S., et al
Bone Marrow Transplantation. 2016;51(5):698-704
Abstract
There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration 120ng/mL versus 43% with concentration >120ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) 10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.