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J Pediatr Hematol Oncol. 2021 Oct 01;43(7):e935-e940. doi: 10.1097/MPH.0000000000002272.

Is Monitoring of Cytomegalovirus Disease Required in Nontransplant Pediatric Acute Lymphoblastic Leukemia?.

Journal of pediatric hematology/oncology

Semra Şen, Hamiyet H Özdemir, Nihal Karadaş, Zümrüt Ş Bal, Şebnem Ö Göktepe, Dilek Ece, Can Balkan, Yeşim Aydinok, Deniz Y Karapinar

Affiliations

  1. Department of Pediatric Infectious Disease, Ege University.
  2. Department of Pediatric Infectious Disease, Celal Bayar University, Manisa, Turkey.
  3. Departments of Pediatric Hematology.
  4. Pediatric Infectious Disease, Ege University Hospital, Izmir.

PMID: 34387629 DOI: 10.1097/MPH.0000000000002272

Abstract

INTRODUCTION: Cytomegalovirus (CMV) infections in developing countries are experienced at an early age. This study was performed to investigate the frequency of reactivation and risk factors of infection acquired at an early age of nontransplant acute lymphoblastic leukemia (ALL) patients receiving immunosuppressive therapy with weekly monitoring of CMV levels in Turkey.

MATERIALS AND METHODS: This was a retrospective, single-center study of 172 pediatric patients (102 boys and 70 girls) with ALL. All patients were monitored routinely for CMV-DNA at the initial presentation of leukemia and twice a week during chemotherapy. The CMV immunoglobulin (Ig)M/IgG titers were measured at admission.

RESULTS: CMV seropositivity at baseline was 90,11%. The overall prevalence of CMV infection (viremia) was 70.34%, 116 of whom were seropositive for CMV IgG and 5 of whom were negative for CMV at the time of ALL diagnosis. Reactivation was more common than de novo CMV infections (P=0.000). CMV seropositivity at the beginning of the leukemia diagnosis was found to be an independent predictor for developing CMV infection (P=0.001). A total of 60 CMV infection episodes were treated with antivirals. Four of these included organ involvement. The duration of CMV-DNA viremia episodes was longer in patients with CMV-DNA ≥1000 copies/mL (n=45) than in those with lower CMV-DNA levels (P=0.002). Infection was shown not to be associated with chemotherapy phase.

CONCLUSION: This study suggests the importance of monitoring for CMV infections in developing countries because of frequent reactivations in seropositive ALL patients. It should be kept in mind that low CMV-DNA levels may also lead to organ involvement.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Conflict of interest statement

The authors declare no conflict of interest.

References

  1. Marchesi F, Pimpinelli F, Ensoli F, et al. Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant. Hematol Oncol. 2017;36:381–391. - PubMed
  2. Rahbarimanesh A, Ehsani M, Karahroudi M, et al. Cytomegalovirus disease in children with acute lymphoblastic leukemia in the non transplant setting: case series and review of the literature. J Pediatr Hematol Oncol. 2015;37:429–432. - PubMed
  3. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Infect Dis Clin North Am. 2010;24:319–337. - PubMed
  4. Mera JR, Whimbey E, Elting L, et al. Cytomegalovirus pneumonia in adult nontransplantation patients with cancer: review of 20 cases occurring from 1964 through 1990. Clin Infect Dis. 1996;22:1046–1050. - PubMed
  5. Jain R, Trehan A, Mishra B, et al. Cytomegalovirus disease in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol. 2016;33:239–247. - PubMed
  6. Han SB, Lee JH, Lee JW, et al. Cytomegalovirus retinitis diagnosed after completion of chemotherapy for acute lymphoblastic leukemia in an adolescent. J Pediatr Hematol Oncol. 2015;37:e128–e130. - PubMed
  7. Samia L, Hamam R, Dbaibo G, et al. Cytomegalovirus retinitis in children and young adults with acute lymphoblastic leukemia in Lebanon. Leuk Lymphoma. 2014;55:1918–1921. - PubMed
  8. Wakai K, Sano H, Shimada A, et al. Cytomegalovirus retinitis during maintenance therapy for T-cell acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2013;35:162–163. - PubMed
  9. Ljungman P, Boeckh M, Hirsch HH, et al. Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis. 2017;64:87–91. - PubMed
  10. Akhter K. Cytomegalovirus. 2018. Available at: https://emedicine.medscape.com/article/215702-overview#a8. Accessed April, 2019. - PubMed
  11. Harrison GJ Cherry J, Demmler-Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ. Cytomegalovirus. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:1969. - PubMed
  12. Ljungman P, Brandan R. Factors influencing cytomegalovirus seropositivity in stem cell transplant patients and donors. Haematologica. 2007;92:1139–1142. - PubMed
  13. Caliendo AM. Approach to the diagnosis of cytomegalovirus infection. 2019. Available at: http://www.uptodate.com. Accessed January 25, 2019. - PubMed
  14. Han XY. Epdemiologic analysis of reactivated cytomegalovirus antigenemia in patients with cancer. J Clin Microbiol. 2007;45:1126–1132. - PubMed
  15. Styczynski J. Who is the patient at risk of CMV recurrence: a review of the current scientific evidence with a focus on hematopoietic cell transplantation. Infect Dis Ther. 2018;7:1–16. - PubMed
  16. Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat Rev Microbiol. 2021;24:1–15. - PubMed
  17. Ataman S, Colak D, Günseren F, et al. Investigation of cytomegalovirus seroepidemiology in Antalya with a population-based cross-sectional study and review of related data in Turkey. Mikrobiyol Bul. 2007;41:545–555. - PubMed
  18. Ek T, Mellander L, Andersson B, et al. Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group. Pediatr Blood Cancer. 2005;44:461–468. - PubMed
  19. El-Chennawi FA, Al-Tonbary YA, Mossad YM, et al. Immune reconstitution during maintenance therapy in children with acute lymphoblastic leukemia, relation to co-existing infection. Hematology. 2008;13:203–209. - PubMed
  20. Moritake H, Kamimura S, Kojima H, et al. Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblatic leukemia. Pediatr Blood Cancer. 2013;60:329–331. - PubMed
  21. Kotton CN, Kumar D, Caliendo AM, et al. The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018;102:900–931. - PubMed
  22. Ljungman P, de la Camara R, Robin C, et al. 2017 European Conference on Infections in Leukaemia group. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019;19:e260–e272. - PubMed
  23. Meesing A, Razonable RR. New developments in the management of cytomegalovirus infection after transplantation. Drugs. 2018;78:1085–1103. - PubMed
  24. Gimeno C, Solano C, Latorre JC, et al. Quantification of DNA in plasma by an automated real-time PCR assay (cytomegalovirus PCR kit) for surveillance of active cytomegalovirus infection and guidance of preemptive therapy for allogeneic hematopoietic stem cell transplant recipients. J Clin Microb. 2018;46:3311–3318. - PubMed
  25. Azevedo LS, Pierrotti LC, Abdala E, et al. Cytomegalovirus infection in transplant recipients. Clinics (Sao Paulo). 2015;70:515–523. - PubMed
  26. Bontant T, Sedlaçek P, Balduzzi A, et al. Survey of CMV management in pediatric allogeneic HSCT programs, on behalf of the inborn errors, infectious diseases and pediatric diseases working parties of EBMT. Bone Marrow Transplant. 2014;49:276–279. - PubMed
  27. Phasuk N, Keatkla J, Rattanasiri S, et al. Monitoring of cytomegalovirus infection in non-transplant pediatric acute lymphoblastic leukemia patients during chemotherapy. Medicine (Baltimore). 2019;98:e14256. - PubMed
  28. Brytting M, Mousavi-Jazi M, Boström L, et al. Cytomegalovirus DNA in peripheral blood leukocytes and plasma from bone marrow transplant recipients. Transplantation. 1995;60:961–965. - PubMed
  29. Kühn JE, Wendland T, Schäfer P, et al. Monitoring of renal allograft recipients by quantitation of human cytomegalovirus genomes in peripheral blood leukocytes. J Med Virol. 1994;44:398–405. - PubMed
  30. Ljungman P, Loré K, Aschan J, et al. Use of a semi-quantitative PCR for cytomegalovirus DNA as a basis for pre-emptive antiviral therapy in allogeneic bone marrow transplant patients. Bone Marrow Transplant. 1996;17:583–587. - PubMed
  31. Moschovi M, Adamaki M, Vlahopoulos SA. Progress in treatment of viral infections in children with acute lymphoblastic leukemia. Oncol Rev. 2016;10:300. - PubMed

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