Study Protocol: Study on Incidence and Risk Factors of Mold Infections in Children During Leukemia Treatment

Incidence and Risk Factors for Invasive Mold Infections in Children During First-Line Chemotherapy for Primary Acute Leukemia: Protocol for a National Retrospective Cohort Study

The study aims to evaluate the occurrence, mortality, and risk factors for invasive mold infections (IMI) in children treated with chemotherapy for acute leukemia in Denmark. The study will be a retrospective nationwide survey study of all children who received first-line chemotherapy for acute leukemia from 2008 to 2022 in Danish pediatric oncology units. The study population includes 621 children under the age of 18. Data will be collected from medical records, hospital databases, and national databases. When the IMI subgroup has been identified, this will be compared to the leukemic group that did not develop IMI. Statistical analysis can then determine the occurrence, mortality rate, and possible IMI risk factors.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute; Acute Lymphoblastic Leukemia

Detailed Description

Chemotherapy can weaken children's immune system, making them vulnerable to infections, including invasive mold infections (IMI), caused mainly by Aspergillus spp. The at-risk population for IMI in children with acquired immunodeficiency is patients with prolonged granulocytopenia due to hematologic malignancies treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients and children receiving long-term corticosteroid treatment. Incidences and mortality rates are often reported as high.

In a retrospective cohort study, we aim to obtain an epidemiological overview of IMI in children receiving first-line treatment for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) in Denmark from 2008 to 2022 and identify possible risk factors, including treatment-related adverse effects.

Objectives

1. To determine and compare the incidence of IMI in childhood AML and ALL during first-line chemotherapy in Denmark.
2. To determine and compare the mortality of IMI in childhood AML and ALL during first-line chemotherapy in Denmark.
3. To explore risk factors for IMI in childhood AML and ALL during first-line chemotherapy in Denmark.

• Study Type: Observational
• Enrollment (Actual): 621

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, DK-5000
    • Rasmus Møller Duus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any patient (<18 years) who initiated first-line chemotherapy against primary ALL or AML at any of the four Danish pediatric oncology departments from January 1st, 2008, to December 31st, 2022.

Description

Inclusion Criteria:

• Age <18 years at the time of inclusion
• Received first-line treatment for ALL or AML
• Treatment at a Danish tertiary pediatric oncology unit (Rigshospitalet, Aarhus University Hospital, Odense University Hospital, and Aalborg University Hospital)
• Treatment initiation January 1st, 2008, to December 31st, 2022

Exclusion Criteria:

• Not meeting inclusion criteria

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of invasive mold infection in childhood AML and ALL in Denmark	The number of subjects in the cohort infected with an invasive mold during leukemia treatment period as defined by the European Organization for Research and Treatment of Cancer Mycoses study group (EORTC/MSG) criteria	Up to three years
Mortality form invasive mold infection in childhood AML and ALL in Denmark.	The number of subjects in the cohort dying from an invasive mold infection during their leukemia treatment period	Up to three years

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Collaborators: Odense University Hospital; Odense Patient Data Explorative Network
• Investigators: Principal Investigator: Rasmus Møller Duus, MD, University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Actual): October 26, 2025
• Study Completion (Actual): October 26, 2025

Study Registration Dates

• First Submitted: March 7, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; childhood; leukemia; lymphoblastic; myeloid; invasive; aspergillus; mold
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Leukemia, Lymphoid; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 22/15850

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data that underlie the results in a future publication will be made publicly available in an anonymized form.
• IPD Sharing Time Frame: The study protocol will be available before collecting participant data. The anonymized participant data will be made available as supplementary material simultaneously with the publication of the article.
• IPD Sharing Access Criteria: All who have access to the article can access the participant data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No