ABSTRACT
Respiratory infections are a common cause of cytopenia in pediatric cancer patients undergoing treatment, with rhinovirus being the most frequent culprit. We aimed to assess the impact of rhinovirus infections during low-intensity chemotherapy maintenance in children with acute lymphoblastic leukemia (ALL). Clinical characteristics and outcomes of patients infected with rhinovirus between 2011-2021 were analyzed. Of the 207 patients on maintenance, 22% presented rhinovirus infection, with 50% experiencing associated cytopenia leading to treatment interruptions in 37%. No increase in relapses or mortality was observed.
These findings suggest that rhinovirus infections can cause bone marrow toxicity during maintenance phase of ALL. Thus, the screening for rhinovirus infection should be considered as part of the investigation in cases of unexpected pancytopenia.
INTRODUCTION
Despite increased survival rates for pediatric cancer, infections remain a major complication. Community-acquired viral respiratory tract infections (VRTIs) are associated with increase of morbidity and mortality, and delays in chemotherapy1.Rhinoviruses (RV) are the most common causative agents.
The clinical presentation of VRTI is nonspecific and depends on patient characteristics such as the underlying disease, chemotherapy and immunosuppression,3.
Rhinoviruses are RNA viruses that circulate year-round, with seasonal peaks. Clinical presentation is variable, with most of the patients presenting with upper VRTI. Immunocompromised patients may have prolonged viral shedding, being challenging to interpret a single positive PCR detection as the causative agent of an actual infection5.
Patients with acute lymphoblastic leukemia (ALL) are expected to present mild neutropenia with normal hemoglobin and platelet count during the maintenance phase due to non-intensive chemotherapy regimen¹. Cases of cytopenia in the context of acute respiratory viral infections in heterogeneous groups of pediatric cancer have been reported3. These patients may need hospital admission, antibiotics, or withdrawal of maintenance chemotherapy.
To determine the impact of RV on the management of patients with ALL and mild-intensity chemotherapy, such as the maintenance cycle, we studied the association between RV infection and cytopenia, as well as the suspension of chemotherapy and the outcome of this group of patients.
PATIENTS AND METHODS
This was a retrospective observational study conducted at the Department of Pediatric Oncology and Hematology of the Vall d’Hebron Hospital, a tertiary hospital in Barcelona (Catalonia, Spain). The local Ethics Committee for Clinical Research approved the study in January 2023 (PR(AMI)42/2023 ).
PATIENTS SELECTION AND DATA COLLECTION
Consecutive symptomatic episodes of RV detection in ALL pediatric patients (< 18 years) in the maintenance phase were included from January 2011 to December 2021. Episodes due to a second positive detection in less than one month were excluded as considered due to prolonged viral shedding. Electronic medical records were reviewed for epidemiological, clinical and microbiological data. Patients were treated according to the LAL-SEHOP-PETHEMA-2013 protocol with M1 referring to oral methotrexate, mercaptopurine and asparaginase plus intrathecal triple therapy and M2 to oral methotrexate and mercaptopurine.
DEFINITIONS
An episode was defined as a positive result in the nasopharyngeal aspirate (NPA) for RV in symptomatic patients without a previous positive test within the last month. Neutropenia was defined as absolute neutrophil count of <1500 cells/ μL and severe neutropenia of <500 cells/μL. Anemia was considered to be present if the hemoglobin (Hb) was below the lower limit of 2 standard deviations (-2SD) for the normal population. Thrombocytopenia was defined as a count of <100000 platelets/μL. Hematological toxicity was evaluated considering the presence of cytopenia, severity, duration and the need for transfusion.
PROCEDURES
Rhinoviruses and other respiratory viruses were detected in respiratory specimens by using a multiplex one-step real-time RT-PCR assay (Allplex Respiratory Panel, Seegene, South Korea). Hematological counts were registered from the same day of the NPA and from previous blood tests to determine each patient’s baseline values
STATISTICAL ANALYSIS
Descriptive analysis was performed using frequency of distributions and means. To compare proportions, a χ2 test was performed. IBM SPSS Statistics® for Windows, Version 25.0. Armonk, NY IBM Corpv was used.
RESULTS