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\begin{document}

\title{Providing Care for Pediatric Cancer Patients in COVID-19 Era; Rapid
Response Recommendations from A Developing Country}



\author[1,2]{Mahmoud Elzembely}%
\author[2]{Yousra  Abdelrahman}%
\author[3]{Shady  Fadel}%
\author[4]{Hanafy Hafez}%
\affil[1]{Assiut University}%
\affil[2]{South Egypt Cancer Institute}%
\affil[3]{Alexandria School of Medicine}%
\affil[4]{National Cancer Institute (NCI), Cairo University}%


\vspace{-1em}



  
  \date{June 10, 2024}


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Coronavirus disease 2019 (COVID-19) was first described in December 2019
in Wuhan, the capital of China's Hubei province.~\textsuperscript{1,2}.
On March 11, 2020, WHO declared COVID-19 as a
pandemic\textsuperscript{3}. The first confirmed case of~COVID-19~in
Egypt was reported on February 14, 2020. As of May 10, 2020, there have
been 8,964 confirmed cases, 2,002 recovered and 514
deaths\textsuperscript{4}.

\textbf{Management of Pediatric Cancer in the COVID-19 ERA}

Children with cancer are immunocompromised and are at higher risk of
developing serious complications because of infection exposure. During
COVID-19 pandemic, many major challenges face pediatric oncologist
regarding the continuity of the anticancer therapy, hospital admission,
infection protection precautions and expected critical complication post
infection in pediatric cancer patients. This raises a question of how to
organize pediatric cancer care in the COVID-19 ERA? We propose some
critical recommendations focusing primarily on viral infection
prevention and control strategies, avoid significant myelosuppression
and decreasing the duration of hospitalization or the use of medical
resources

\textbf{Our recommendations include:}

\emph{\textbf{Screening and surveillance:}}

All patients and their care givers should be screened with
epidemiological history and screening questionnaires according to the
updated COVID-19 case definition at a well-equipped station better to be
at facility entrance. Suspected cases should be immediately isolated in
an area separate from other patients. Medical workers caring for
isolated patients should not care for regular patients in the oncology
ward.

\emph{\textbf{Apply Hand and respiratory hygiene:}}

Hand and respiratory hygiene should be strictly applied for patients,
care givers and health workers\textsuperscript{5}. Proper personal
protective equipment should be used according to WHO
guidance\textsuperscript{6}.

\emph{\textbf{Apply principles of social distancing:}}

Principles of social distancing should be applied through isolating
patients in separate rooms and if not possible arrange patients' beds
with 2 meters distance at least, only one caregiver is allowed during
hospital admission or in outpatient clinic, no visitors are allowed and
distancing patients in the waiting area by at least 2 meters

\emph{\textbf{Prioritize Pediatric Cancer Care:}}

\textbf{For newly diagnosed cases:}

Patient should proceed with their diagnostic procedures without delay.
Diagnostic procedures should be performed as an outpatient procedure
unless otherwise required by the treating physicians.

\textbf{For patients on active curative treatment}

Treatment protocols need to be modified to decrease hospitalization and
decrease the duration of neutropenia without survival impairment.

\emph{\textbf{Hematological Malignancies}}

\textbf{Acute lymphoblastic leukemia:}

Patients are treated according to modified St. Jude total
XV\textsuperscript{7} protocol. We propose:

1-Giving granulocyte colony stimulating factors (GCSFs) during induction
chemotherapy if BMA at D19 is in complete remission and after induction
chemotherapy before consolidation.

2-Delaying consolidation and giving weekly methotrexate (MTX)/
6-mercaptopurine (MP) for 2 weeks as interim continuation if BMA at the
end of induction is MRD negative

3-During consolidation, reduction of the 6 MP dose by 50\% with close
assessment of total leucocytic counts.

4- During continuation: for low risk patients, omitting vincristine
(VCR)/dexamethasone (DEX) pulses and use only MTX/ 6MP in the addition
to re-induction weeks and for high risk patients, no change
L-asparaginase and reinduction weeks, omitting weeks of
cyclophosphamide/cytarabine and use MTX/6MP alternating with VCR/DEX.
These modifications are based on randomized controlled study by Felice
et al\textsuperscript{8}.~ Felice et al., performed a randomized
controlled study comparing between continuation regimens consisting of
MTX/6MP or rotating pairs of drugs in low risk ALL patients and
continuation regimens consisting of MTX/6MP alternating with VCR/DEX~~
or rotating pairs of drugs for SR/HR ALL patients. They found no
statistically significant difference in outcome between arms of
maintenance for both risk groups. They also found that rotating drug
pairs regimen was associated with significantly more febrile neutropenia
episodes and prolonged hospitalization . These modifications allow less
clinical visits to hospital by extended dispensing of continuation
chemotherapy

\textbf{Acute Myeloid leukemia:}

Patients are treated according to modified St. Jude AML 02
protocol\textsuperscript{9}, we propose the following recommendations:

\begin{enumerate}
\tightlist
\item
  Induction chemotherapy: Omit etoposide so induction consists of Ara-C
  and Doxorubicin based on Medical research council AML 15 clinical
  trial\textsuperscript{10}.
\item
  The use of G-CSF during induction chemotherapy 24 hours after
  chemotherapy and 48 hours before the next cycle of chemotherapy if BMA
  at D15 less than 5\%.
\end{enumerate}

\textbf{Non-hodgkin lymphoma including mature B ALL:}

We recommend using growth factors pre-emptively 24 hours after
completion of chemotherapy.

\textbf{Hodgkin lymphoma, classic type}

Patients are treated according to EuroNet-PHL-CI clinical trial. We
propose the use of OEPA and COPDAC chemotherapy as multiple day regimens
in the day care without admission

\emph{\textbf{Solid Tumors:}}

\textbf{We recommend}

\begin{enumerate}
\tightlist
\item
  Use of growth factors pre-emptively 24 hours after completion of
  chemotherapy
\item
  Shift of chemotherapy protocols as a day care outpatient therapy if
  possible, without endangering patients with possible adverse effects
  as nephrotoxicity.
\item
  Delay all therapies beyond 1\textsuperscript{st} line therapy unless
  there is urgent clinical situation
\item
  Delay imaging procedures to monitor response to treatment unless
  urgent clinical condition
\end{enumerate}

\textbf{}\emph{\textbf{Patients on palliative care therapy}}

Palliative care patients need to be evaluated case by case as delay in
palliative care may result in more suffering and subsequently more
hospitalization.

\textbf{We recommend the following:}

\begin{enumerate}
\tightlist
\item
  Patients on chemotherapy: Delay palliative chemotherapy and use less
  aggressive regimens
\item
  Patients on pain medications: Give patient a stock of pain medications
  for a longer time
\item
  Use of telemedicine to communicate with patients to determine the need
  for hospital visit
\end{enumerate}

\emph{\textbf{Follow up patients:}}

We recommend disease free patient not to visit the hospital, using
telemedicine for communication with pediatric cancer survivors and
exchange medical documents

\textbf{Conclusion}

We are trying to offer the optimal care for those critical patients,
keeping their chances of cure from cancer and on the same way minimizing
their exposure and risk for COVID19 pandemic infection and maintaining
safe environment for both patients and healthcare providers.

\emph{References}

\begin{enumerate}
\tightlist
\item
  Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W.,
  \ldots{} \& Chen, H. D. (2020). A pneumonia outbreak associated with a
  new coronavirus of probable bat origin.~\emph{Nature} ,~\emph{579}
  (7798), 270-273.
\item
  Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., \ldots{} \&
  Niu, P. (2020). A novel coronavirus from patients with pneumonia in
  China, 2019.~\emph{New England Journal of Medicine} .
\item
  ''WHO Director-General's opening remarks at the media briefing on
  COVID-19''
  (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020).
  World Health Organization (WHO) (Press release). 11 March 2020.
  Archived
  (https://web.archive.org/web/20200311212521/https://www.who.int/dg/speeches/detail/who-director-general-sopening-remarks-at-the-media-briefing-on-covid-19---11-march-2020)
  from the original on 11 March 2020. Retrieved 10 May 2020.
\item
  ''https://www.worldometers.info/coronavirus/'', Author:
  Worldometers.info, Publishing Date: 10 May, 2020, Place of
  publication: Dover, Delaware, U.S.A.
\item
  World Health Organization. (2020). Infection prevention and control
  during health care when COVID-19 is suspected: interim guidance, 19
  March 2020 (No. WHO/2019-nCoV/IPC/2020.3). World Health Organization.
\item
  World Health Organization. (2020). Rational use of personal protective
  equipment for coronavirus disease ( COVID-19) and considerations
  during severe shortages: interim guidance, 6 April 2020 (No.
  WHO/2019-nCov/IPC\_PPE\_use/2020.3). World Health Organization.
\item
  Pui, C. H., Relling, M. V., Sandlund, J. T., Downing, J. R., Campana,
  D., \& Evans, W. E. (2004). Rationale and design of Total Therapy
  Study XV for newly diagnosed childhood acute lymphoblastic
  leukemia.~\emph{Annals of hematology} ,~\emph{83} , S124-6.
\item
  Felice MS, Rossi JG, Gallego MS, et al.: No advantage of a rotational
  continuation phase in acute lymphoblastic leukemia in childhood
  treated with a BFM back-bone therapy. Pediatr Blood Cancer 57
  (1):47-55, 2011
\item
  Rubnitz, J. E., Inaba, H., Dahl, G., Ribeiro, R. C., Bowman, W. P.,
  Taub, J., \ldots{} \& Meshinchi, S. (2010). Minimal residual
  disease-directed therapy for childhood acute myeloid leukaemia:
  results of the AML02 multicentre trial.~\emph{The lancet oncology}
  ,~\emph{11} (6), 543-552.
\item
  Burnett, A. K., Russell, N. H., Hills, R. K., Hunter, A. E., Kjeldsen,
  L., Yin, J., \ldots{} \& Milligan, D. (2013). Optimization of
  chemotherapy for younger patients with acute myeloid leukemia: results
  of the medical research council AML15 trial.~\emph{Journal of clinical
  oncology} ,~\emph{31} (27), 3360-3368.
\end{enumerate}

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