Hematological complications
Fifty percent of episodes were associated with at least one new
cytopenia. Among patients with a decrease in their hemoglobin values,
86% had a value in the range for anemia. Regarding the drop in the
platelet level, 35% achieved levels below 100.000 platelets/μL. About
the decrease in the neutrophil count, 96% were in the range for
neutropenia, being severe in 23% of them.
To rule out confusion factors, type of maintenance and co-infection were
analyzed in relation with cytopenia incidence. No statistically
differences were found, neither with chemotherapy regimen (M1 46% vs.
M2 54%, p value 0.157) nor co-infection (co-infection 58.3%, no
co-infection 48.9%, p value 0.560).
A delay in chemotherapy occurred in 32.7% with a median duration of the
treatment withdrawal of 7 days (IQR 4). Bone marrow aspiration (BMA) was
performed in 8.1% due to prolonged cytopenia, and immunophenotype ruled
out relapse. There were two relapses, both in patients without treatment
withdrawal. No microbiological studies were performed. No deaths were
recorded.
Complete data is summarized in table II .
DISCUSSION
In our study, children with ALL and RV infection presented with a
mild disease, but cytopenia were common and led to increased
chemotherapy delays. Nonetheless, no relapses were detected in these
patients
Many publications report the impact of viral infections in hematological
patients3,5, but little is known concerning the
association between RV infection and aplasia. The few previous
reports showed a similar rate of RV laboratory-confirmation,
ranging from 30% to 76%5. Data on co-infection is
consistent with previously published studies
(19-20%)3,5.
In our study, cytopenia were detected in 52.4% of cases, and 44.2%
presented with a low neutrophil count. This was in line with Aydın
Köker et al study³, which reported a 42% rate of neutropenia
associated with RV infection and a 33% rate of chemotherapy delays
compared to our 32.7%.
Other causes of aplasia (asparaginase use and
co-infections3) were not related to its incidence,
suggesting that RV infection may be an independent risk factor
for aplasia.
Treatment continuity during maintenance has a significant impact on its
response, so delays should be avoided8. Despite this,
we did not find any relapse events during the follow-up of patients in
whom chemotherapy was discontinued in relation to RV- related
cytopenia.
This study has some limitations. It is a retrospective, single-center
study that may limit data collection, but our electronic medical record
minimizes potential loss of information. The use of a single-point PCR
RV detection may incorrectly preclude RV as the cause of
infection in a population with prolonged viral shedding. To minimize
this, we excluded those with a recent detection. The fact that the study
ends in December 2021 could cause some detection bias since NPAs were
more commonly performed from March 2020 due to the COVID-19 pandemic.
Lastly, RV testing was not performed in BMA to rule out a direct
cytopathic virus effect.
In conclusion, in our series, RV infection during maintenance treatment
was frequent, causing cytopenia in half of the patients and delays in
chemotherapy in one out of three, without increasing the risk of
relapse. Thus, screening for rhinovirus infection should be considered
as part of the investigation in cases of unexpected pancytopenia during
maintenance treatment, particularly during the colder months.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no conflict of interest.
AKNOWLEDGEMENTS
We would like to thank all our colleagues from the Oncology and
Hematology, Infectious Diseases, and Microbiology departments involved
in the care of the patients featured in this study. We also want to
express our special gratitude to Dr. Ángela Menárguez and Dr. Eva
Castilla, who spearheaded the creation of the pediatric database for
patients with acute lymphoblastic leukemia, without which this project
would not have been possible.
Lastly, we extend our heartfelt appreciation to all the patients and
their families for contributing to the advancement of knowledge about
childhood cancer.
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