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