Risk factors associated with development and mortality by invasive fungal diseases in pediatric allogeneic stem cell transplantation. A pediatric subgroup analysis of data from a prospective study of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Castagnola, Elio; Bagnasco, Francesca; Menoni, Stefania; Muraca, Monica; Prete, Arcangelo; Belotti, Tamara; Iori, Anna Paola; Barberi, Walter; Severino, Alessandro; Proia, Anna; Raiola, Anna Maria; Vacca, Adriana; Cudillo, Laura; Girmenia, Corrado

doi:10.1038/s41409-018-0160-2

Cited by 8 publications

(6 citation statements)

References 17 publications

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“…32 Older age has been shown to confer risk for IFD in some other studies, 35,36,44 but other studies, including ours, did not find this association. 2,30,34 As expected, based on previous studies, 2,19,36,[45][46][47][48][49] all patients had severe neutropenia, though patients with IFD were neutropenic for longer prior to first fever.…”

Section: Discussionsupporting

confidence: 76%

“…ALL was associated with IFD in our study, most prominently in those with active leukemia in their bone marrow undergoing 4‐drug induction 32 . Older age has been shown to confer risk for IFD in some other studies, 35,36,44 but other studies, including ours, did not find this association 2,30,34 . As expected, based on previous studies, 2,19,36,45–49 all patients had severe neutropenia, though patients with IFD were neutropenic for longer prior to first fever.…”

Section: Discussionsupporting

confidence: 76%

“…An initial list of potential predictors of IFD was created a priori based on published guidelines, 4 previous studies in the field, 2,30–36 and clinical practice at our institution. This list was then narrowed to focus on predictors that had a sound physiologic connection to IFD and would be readily accessible at most institutions.…”

Section: Methodsmentioning

confidence: 99%

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A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients

Whitehurst,

Friedman,

Zhao

et al. 2023

Pediatric Blood & Cancer

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BackgroundPediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/μL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta‐D‐glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population.MethodsIn a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005‐2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified.ResultsIn total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non‐IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice.ConclusionsChest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 76%

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A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients

Whitehurst,

Friedman,

Zhao

et al. 2023

Pediatric Blood & Cancer

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“…Acute GVHD, particularly high‐grade GVHD, has been reported as a potential risk factor for IFD in several single‐centre studies (Hovi et al ., ; Hale et al ., ; Srinivasan et al ., ), as well as one retrospective, multicentre study (Hazar et al ., ). Similarly, chronic GVHD has been identified as a risk factor for IFD (Hovi et al ., ; Kobayashi et al ., ; Hale et al ., ; Srinivasan et al ., ; Castagnola et al ., ). Data are limited with respect to specific therapies for GVHD; however, calcineurin inhibitors alone are rarely associated with IFD.…”

Section: Children At Risk For Invasive Fungal Diseasementioning

confidence: 97%

Fungal infections in children with haematologic malignancies and stem cell transplant recipients

Otto

Green

2020

Br J Haematol

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Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions.

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“…[1][2][3][4][5][6] The incidence of IFIs after allo-HSCT ranged from 3%-24% depending on pre-HSCT underlying disease, antifungal prophylaxis protocols, and IFI definitions. 1,[7][8][9][10] During the pre-engraftment period (less than day+40 post allo-HSCT), infections with Candida species were common until implementation of antifungal prophylaxis in the 1990s when infections with azole-resistant Candida species and molds were increasingly documented. 11,12 Subsequent studies have identified potential risk factors for IFIs after allo-HSCT including prolonged neutropenia, graft-versus-host disease (GVHD), and augmented immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

Chuleerarux

Nematollahi

Thongkam

et al. 2022

Clinical Microbiology and Infection

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Risk factors associated with development and mortality by invasive fungal diseases in pediatric allogeneic stem cell transplantation. A pediatric subgroup analysis of data from a prospective study of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Cited by 8 publications

References 17 publications

A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients

A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients

Fungal infections in children with haematologic malignancies and stem cell transplant recipients

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

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