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\begin{document}

\title{Reactogenicity of influenza vaccination in children with cancer and
hematologic diseases.}



\author[1]{Almudena Laris-González}%
\author[2]{Martha Aviles-Robles}%
\author[2]{Sarbelio Moreno-Espinosa}%
\author[2]{Rodolfo Jiménez-Juárez}%
\affil[1]{Hospital Infantil de México Federico Gomez}%
\affil[2]{Hospital Infantil de Mexico Federico Gomez}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\textbf{LETTER TO THE EDITOR}

\textbf{REACTOGENICITY OF INFLUENZA VACCINATION IN CHILDREN WITH CANCER
AND HEMATOLOGIC DISEASES}

\textbf{Authors:}

Almudena Laris-Gonz\selectlanguage{ngerman}ález (1), Martha Avilés-Robles (1), Sarbelio Moreno
Espinosa (2), Rodolfo Jiménez-Juárez (1,3).

\emph{Affiliation:}

1. Hospital Infantil de México Federico Gómez. Department of Infectious
Diseases.

2. Hospital Infantil de México Federico Gómez. Director of Education.

3. Hospital de Infectología ''Daniel Méndez Hernández'', UMAE CMN La
Raza, IMSS. Department of Pediatrics.

\emph{Corresponding author} : Rodolfo Jiménez-Juárez

Hospital Infantil de México Federico Gómez. Department of infectious
Diseases.

Dr. Márquez 162, Cuauhtemoc, 06720, Ciudad de México, México.

Phone number: (52) 55 4342 8293. Email: dr.jimenezjuarez@gmail.com

\textbf{Word count:} 496

\textbf{Tables:} 1

\textbf{Running title:} Influenza vaccination in children with cancer.

\textbf{Keywords:} Influenza vaccine, adverse reactions, reactogenicity,
children, cancer, hematologic diseases

To the Editor:

Patients with cancer are at increased risk of influenza related
hospitalization and death.\textsuperscript{1} Influenza vaccine has been
proven safe in adults with cancer,\textsuperscript{2,3} but
reactogenicity in pediatric patients has been poorly
characterized.\textsuperscript{4}

All patients in the oncology and hematology clinic in a referral
pediatric hospital in Mexico City who received the trivalent inactivated
influenza vaccine during the 2020-2021 season were invited to
participate in a telephone survey regarding adverse reactions to
vaccination.

A questionnaire covering systemic and local symptoms, as well as the
need for medical care or hospitalization was applied at days three,
seven and fourteen after vaccination. The clinical record was reviewed
in case of hospitalization.

Ninety children vaccinated from October 2020 to February 2021 agreed to
participate and were included in the study; 54\% were male and the
median age was 9 years (interquartile range 6.7-14 years). Fifteen
patients had a non-malignant hematologic disease and the rest had a
diagnosis of cancer. The most frequent underlying conditions were acute
leukemias (n= 37 acute lymphoblastic leukemia and 4 acute myeloid
leukemia), malignant bone tumors (n= 8), lymphomas (n= 5), Langerhans
cell histiocytosis (n= 4) and hemophilia A (n= 4).

Twenty-seven patients experienced any local or systemic reactions after
vaccination. Pain in the site of injection was the most frequent symptom
(22.2\%), followed by headache (5.6\%), fever (4.4\%) and myalgias
(4.4\%). Most events were mild and resolved within 2 days (Table 1). No
adverse reactions requiring medical attention were documented.

No patient experienced solicited or unsolicited adverse reactions after
day three. One patient with hematopoietic stem-cell transplantation and
graft-versus-host disease was vaccinated during a prolonged
hospitalization and had fever for one day, with no other reactions
reported. No patient required hospital admission in the fourteen days
after vaccination.

Our findings are in line with those of a systematic review from 2013
which found no life-threatening events after influenza vaccination among
391 pediatric patients receiving chemotherapy for cancer. Low-grade
fever and mild local reactions were no greater in children with cancer
compared with healthy controls.\textsuperscript{4}

A small randomized trial comparing the high-dose to the standard-dose
trivalent influenza vaccine in children with acute lymphoblastic
leukemia found no severe adverse events related to vaccination in any
group.\textsuperscript{5} The most frequent adverse events were fatigue,
pain and tenderness in the injection site. Most events were grades 1 or
2.

Individuals with hematologic diseases and those receiving chemotherapy
for cancer are considered among high-risk groups who should be
prioritized for influenza vaccination.\textsuperscript{6} However, a low
compliance with immunization in this group of patients has been reported
which could be related to a variety of factors, including lack of
awareness of recommendations and concerns regarding efficacy and
side-effects of vaccination.\textsuperscript{7-9}

In conclusion, influenza vaccination appears to have a good
reactogenicity profile among children with hematologic and oncologic
diseases. Education regarding safety and efficacy of vaccination should
be reinforced among caregivers of patients with increased risk of
complications and their healthcare providers, and their concerns should
be addressed to improve vaccine compliance.

\textbf{Conflicts of Interest:} RJJ and SME have received research
grants from Sanofi-Pasteur. ALG, MAR, SME and RJJ have received payment
for lectures from Sanofi-Pasteur. ALG and SME has also received payment
for lectures from Roche.

\textbf{Acknowledgements:} We are pleased to acknowledge María Teresa
Ramírez Antonio, Diana Rosas de Santiago, Maribel Benítez Vega, Genoveva
Peña Carrillo, Griselda Moreno Salmerón and Nayeli Del Carmen De Leon
Briseño, who were involved in vaccination, informed consent and
telephone surveys.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Cooksley CD, Avritscher EB, Bekele BN, et al. Epidemiology and
  outcomes of serious influenza-related infections in the cancer
  population. Cancer 2005; 104:618--628.
\item
  Shehata MA, Karim NA. Influenza vaccination in cancer patients
  undergoing systemic therapy. Clin Med Insights Oncol. 2014 May
  1;8:57-64. doi: 10.4137/CMO.S13774.
\item
  Bitterman R, Eliakim-Raz N, Vinograd I, Zalmanovici Trestioreanu A,
  Leibovici L, Paul M. Influenza vaccines in immunosuppressed adults
  with cancer. Cochrane Database Syst Rev. 2018 Feb 1;2(2):CD008983.
  doi: 10.1002/14651858.CD008983.pub3.
\item
  Goossen GM, Kremer LC, van de Wetering MD. Influenza vaccination in
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  10.1002/14651858.CD006484.pub3.
\item
  McManus M, Frangoul H, McCullers JA, Wang L, O'Shea A, Halasa N.
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\item
  Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and Control of
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\item
  Wumkes ML, van der Velden AM, van der Velden AW, Stouthard JM, Nijziel
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\item
  Vinograd I, Baslo R, Eliakim-Raz N, Farbman L, Taha A, Sakhnini A, et
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\item
  Loulergue P, Mir O, Alexandre J, Ropert S, Goldwasser F, Launay O. Low
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\end{enumerate}

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