Main Article Content

Seung Beom Han *
Ju Ae Shin
Seong koo Kim
Jae Wook Lee
Dong-Gun Lee
Nack-Gyun Chung
Bin Cho
Dae Chul Jeong
Jin Han Kang
(*) Corresponding Author:
Seung Beom Han |


Background: Despite the introduction of a polymerase chain reaction (PCR) test for the diagnosis of respiratory viral infection (RVI), guidance on the application of this test and the management of RVI in immunocompromised children is lacking. This study evaluated the clinical characteristics of RVI and established strategies for the PCR test in children and adolescents with hematological malignancies.
Methods: This study included children and adolescents with underlying hematological malignancies and respiratory symptoms, in whom a multiplex PCR test was performed. Patients in whom RVI was identified and not identified were categorized into Groups I and II, respectively. Group I was sub-divided into patients with upper and lower respiratory infections. The medical records of the enrolled patients were retrospectively reviewed.
Results: A total of 93 respiratory illnesses were included. Group I included 46 (49.5%) cases of RVI, including 31 (67.4%) upper and 15 (32.6%) lower respiratory infections. Rhinovirus (37.0%) was the most common viral pathogen. Significantly more patients in Group I had community-acquired respiratory illnesses (p=0.003) and complained of rhinorrhea (p<0.001) and sputum (p=0.008) than those in Group II. In Group I, significantly more patients with lower respiratory infections had uncontrolled underlying malignancies (p=0.038) and received re-induction or palliative chemotherapy (p=0.006) than those with upper respiratory infections.
Conclusions: A multiplex PCR test should be considered for RVI diagnosis in immunocompromised children and adolescents with respiratory symptoms, especially in those with rhinorrhea or sputum prominent over a cough. The early application of the PCR test in patients with uncontrolled underlying malignancies may improve outcomes.

Keywords: child, hematologic neoplasms, polymerase chain reaction, respiratory tract infections

Downloads month by month


Download data is not yet available.

Article Details


1. Hersh EM, Bodey GP, Nies BA, Freireich EJ. Causes of death in acute leukemia: a ten-year study of 414 patients from 1954-1963. JAMA. 1965;193(2):105-109.
2. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-93.
3. Castagnola E, Fontana V, Caviglia I, Caruso S, Faraci M, Fioredda F, Garrè ML, Moroni C, Conte M, Losurdo G, Scuderi F, Bandettini R, Tomà P, Viscoli C, Haupt R. A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin Infect Dis. 2007;45(10):1296-1304.
4. Hakim H, Flynn PM, Knapp KM, Srivastava DK, Gaur AH. Etiology and clinical course of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol. 2009;31(9):623-629.
5. Lindblom A, Bhadri V, Söderhäll S, Ohrmalm L, Wong M, Norbeck O, Lindau C, Rotzén-Ostlund M, Allander T, Catchpoole D, Dalla-Pozza L, Broliden K, Tolfvenstam T. Respiratory viruses, a common microbiological finding in neutropenic children with fever. J Clin Virol. 2010;47(3):234-237.
6. Koskenvuo M, Möttönen M, Rahiala J, Saarinen-Pihkala UM, Riikonen P, Waris M, Ziegler T, Uhari M, Salmi TT, Ruuskanen O. Respiratory viral infections in children with leukemia. Pediatr Infect Dis J. 2008;27(11):974-980.
7. Maeng SH, Yoo HS, Choi SH, Yoo KH, Kim YJ, Sung KW, Lee NY, Koo HH. Impact of parainfluenza virus infection in pediatric cancer patients. Pediatr Blood Cancer. 2012;59(4):708-710.
8. Raboni SM, Nogueira MB, Tsuchiya LR, Takahashi GA, Pereira LA, Pasquini R, Siqueira MM. Respiratory tract viral infections in bone marrow transplant patients. Transplantation. 2003;76(1):142-146.
9. Chemaly RF, Ghosh S, Bodey GP, Rohatgi N, Safdar A, Keating MJ, Champlin RE, Aguilera EA, Tarrand JJ, Raad II. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore). 2006;85(5):278-287.
10. Ljungman P, Ward KN, Crooks BN, Parker A, Martino R, Shaw PJ, Brinch L, Brune M, De La Camara R, Dekker A, Pauksen K, Russell N, Schwarer AP, Cordonnier C. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2001;28(5):479-484.
11. Murali S, Langston AA, Nolte FS, Banks G, Martin R, Caliendo AM. Detection of respiratory viruses with a multiplex polymerase chain reaction assay (MultiCode-PLx Respiratory Virus Panel) in patients with hematologic malignancies. Leuk Lymphoma. 2009;50(4):619-624.
12. Torres JP, De la Maza V, Kors L, Villarroel M, Piemonte P, Izquierdo G, Salgado C, Tordecilla J, Contardo V, Farfán MJ, Mejías A, Ramilo O, Santolaya ME. Respiratory viral infections and coinfections in children with cancer, fever and neutropenia: clinical outcome of infections caused by different respiratory viruses. Pediatr Infect Dis J. 2016;35(9):949-954.
13. Srinivasan A, Gu Z, Smith T, Morgenstern M, Sunkara A, Kang G, Srivastava DK, Gaur AH, Leung W, Hayden RT. Prospective detection of respiratory pathogens in symptomatic children with cancer. Pediatr Infect Dis J. 2013;32(3):e99-e104.
14. Benites EC, Cabrini DP, Silva AC, Silva JC, Catalan DT, Berezin EN, Cardoso MR, Passos SD. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy. J Pediatr (Rio J). 2014;90(4):370-376.
15. Suryadevara M, Tabarani CM, Bartholoma N, Rosenberg HF, Domachowske JB. Nasopharyngeal detection of respiratory viruses in febrile neutropenic children. Clin Pediatr (Phila). 2012;51(12):1164-1167.
16. Milano F, Campbell AP, Guthrie KA, Kuypers J, Englund JA, Corey L, Boeckh M. Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem cell transplantation recipients. Blood. 2010;115(10):2088-2094.
17. Lo MS, Lee GM, Gunawardane N, Burchett SK, Lachenauer CS, Lehmann LE. The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy. Pediatr Transplant. 2013;17(2):133-143.
18. Machado AF, Sallum MA, Vilas Boas LS, Tateno AF, Machado CM. Molecular characterization of strains of respiratory syncytial virus identified in a hematopoietic stem cell transplant outpatient unit over 2 years: community or nosocomial infection? Biol Blood Marrow Transplant. 2008;14(12):1348-1355.
19. Kassis C, Champlin RE, Hachem RY, Hosing C, Tarrand JJ, Perego CA, Neumann JL, Raad II, Chemaly RF. Detection and control of a nosocomial respiratory syncytial virus outbreak in a stem cell transplantation unit: the role of palivizumab. Biol Blood Marrow Transplant. 2010;16(9):1265-1271.
20. Maziarz RT, Sridharan P, Slater S, Meyers G, Post M, Erdman DD, Peret TC, Taplitz RA. Control of an outbreak of human parainfluenza virus 3 in hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2010;16(2):192-198.
21. Shah DP, Ghantoji SS, Shah JN, El Taoum KK, Jiang Y, Popat U, Hosing C, Rondon G, Tarrand JJ, Champlin RE, Chemaly RF. Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections. J Antimicrob Chemother. 2013;68(8):1872-1880.
22. Waghmare A, Englund JA, Boeckh M. How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation. Blood. 2016;127(22):2682-2692.
23. Torres HA, Aguilera EA, Mattiuzzi GN, Cabanillas ME, Rohatgi N, Sepulveda CA, Kantarjian HM, Jiang Y, Safdar A, Raad II, Chemaly RF. Characteristics and outcome of respiratory syncytial virus infection in patients with leukemia. Haematologica. 2007;92(9):1216-1223.
24. Seo S, Xie H, Campbell AP, Kuypers JM, Leisenring WM, Englund JA, Boeckh M. Parainfluenza virus lower respiratory tract disease after hematopoietic cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis. 2014;58(10):1357-1368.
25. Seo S, Waghmare A, Scott EM, Xie H, Kuypers JM, Hackman RC, Campbell AP, Choi SM, Leisenring WM, Jerome KR, Englund JA, Boeckh M. Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality. Haematologica. 2017;102(6):1120-1130.
26. Shah DP, Shah PK, Azzi JM, Chemaly RF. Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review. Cancer Lett. 2016;370(2):358-364.
27. Shah DP, Ghantoji SS, Ariza-Heredia EJ, Shah JN, El Taoum KK, Shah PK, Nesher L, Hosing C, Rondon G, Champlin RE, Chemaly RF. Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections. Blood. 2014;123(21):3263-3268.
28. Couch RB, Englund JA, Whimbey E. Respiratory viral infections in immunocompetent and immunocompromised persons. Am J Med. 1997;102(3A):2-9; discussion 25-26.