Febrile Episodes during Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia at Children Hospital –Benghazi 2013-2014
Asian Journal of Pediatric Research,
Page 25-34
DOI:
10.9734/ajpr/2022/v8i430253
Abstract
Patients undergoing chemotherapy are vulnerable to infection because of immunosuppression and prolonged hospitalizations. Chemotherapy drugs affect neutrophil production through myelosuppression (1) and low inflammatory response so that fever maybe the manifestation of infection (2).
The purpose of this study was to analyze febrile neutropenic episodes associated with infections in the 1st three phases of acute lymphoblastic leukemia (ALL) treatment, document the risk factors affecting morbidity, mortality, treatment and the outcome of treatment.
The study was a cross-sectional hospital-based descriptive survey in the Hematology-Oncology Unit at Children’s Hospital. It included all cases of (ALL) who were diagnosed within two years and treated with the Berlin Frankfurt Munich (BFM) protocol who developed fever during a neutropenic period. Data was recorded as gender, age, residence, nationality, number of episodes per patient, treatment phase, admission duration, length of stay (LOS) per episode, symptoms, physical examination and severity of fever. Investigations, the antibiotic used and the outcome were also recorded.
A total 27children, males accounting for 63%, 67<5 were included in the study. Febrile neutropenic episodes ranged 1–12. Their peak was in January. 40% were in phase II. LOS range 2-35 days. Fever showed a median of 38.8 °C, higher in phase II and III. Admission and therapy phases were longer in children ˂ 2 years old and in males. The neutrophil median was 270/mm3. Stomatitis was seen in70% of episodes, gastroenteritis in 65%, fever of unknown origin (FUO) in 16%and pneumonias in 15%. 20/23 bacterial infections were Gram-negative. 40% of episodes required a change of antibiotics. The mortality rate was 22%.
Keywords:
- Acute lymphoblastic leukemia
- neutropenia
- fever
- Children’s Benghazi
- Libya
How to Cite
Alzehawi, S. M. M., Beayou, A., Elgazal, N. B., Khalifa, F. S., Alabeedi, S. S., & Alferjani, M. M. (2022). Febrile Episodes during Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia at Children Hospital –Benghazi 2013-2014. Asian Journal of Pediatric Research, 8(4), 25-34. https://doi.org/10.9734/ajpr/2022/v8i430253
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Peng LH, Keng TC, Sinniah D. Fever in children with acute lymphoblastic leukemia. 1 February 1981;47(3):583–587.
Martina Söderman, Samuel Rhedin. Frequent Respiratory Viral Infections In Children With Febrile Neutropenia - aprospective follow-up study. Sweden. PLoS ONE. 11(6):e0157398.
Claire Ann B. Celiz-Pascual. MD Robert Dennis Garcia, infections in febrile neutropenic cancer patients who were undergoing chemotherapy at the Makati medical center. Makati Medical Philippines Center Pidsp Journal. 2011;12(1):165-71.
Bertone R, Candoni D, Russo M, Michieli D. Neutropenic patients with unexplained fever. La Sapienza University of Rome, Italy. Clin Infect Dis. 2003;17(Suppl 2):S378-84.
Pitiya R, Chusana S. Causative pathogens of fever in neutropenic patients at King Chulalongkorn Memorial Hospital. J Med Assoc Thai. 2010;93(7):776-83.
Hann I, Viscoli C, Paesmans M, Gaya H, Glauser M. A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies. International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC). Br J Haematol. 2012;99(3):580-8.
Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R, et al. 2011 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis. 2013;25(3):551- 73.
Viscoli C, Cometta A, Kern WV, Bock R, Paesmans M, Crokaert F, Glauser MP, Calandra T. International Antimicrobial Therapy Group of the European Organization for Research and Treatment of Cancer. Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients. Clin Microbiol Infect. 2006;12:212-216.
Thomas l. Robert phillips, Sarah alexander.et al. Neutropenia in children with malignanacy. Journal of Clinical Oncology. December 2012;30(35):4427-4438.
Olkinuora H, Rahiala J, Anttila VJ, Koskenvuo M, Vettenranta K. Immune deficiency and infections in children having cancer. .Article in Finnish Duodecim. 2013;129(12):1233-41.
Hadir M. Meir, MD, Ibrahim A. Balawi, MD, Hala M. Meer, MD, Hala Nayel, MD, Mohammad F. Al-Mobarak, MD. Fever and granulocytopenia in children with Acute Lymphoblastic Leukemia under induction therapy. Saudi Med J. 2001;22(5):423-427.
Zeina A. Kanafani Ghenwa K. Dakdouki Khalil I. El-Chammas Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon International Journal of Infectious Diseases September 2007;11(5)450–453.
Christina Orasch, Catherine Cordonnier, Murat Akova. European guideline for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance summary of the 2011 4th European Conference on Infections in Leukemia. J Pediatr Hematol Oncol. 2012;24(1):38-42.
Hyypiä T, Puhakka T, Ruuskanen O, Mäkelä M, Arola A, Arstila P. Infections in a pediatric patient cohort with acute lymphoblastic leukemia during consolidation. J Clin Microbiol. 2008; 36(7):2081-3.
Lie SO, Gustafsson G. Progress in the treatment of childhood leukaemias. Ann Med; 1992.
Minna Koskenvuoand Painosalama Oy. Febrile infections in children with leukemia, with special reference to respiratory viral infections Pediatrics Annales Universitatis Turkuensis, Medica-Odontologica. 2008; 18(13):2522-8.
Chong CY, Tan AM, Lou J. Infections in acute lymphoblastic leukaemia. Women’s and Children’s Hospital Ann Acad Med Singapore. 2008;27:491-5.
Bakhshi S1, Padmanjali KS, Arya LS. Infections in childhood acute lymphoblastic leukemia. New Delhi, India Pediatr Hematol Oncol. 2008 Jun;25(5):385.
Juan Enrique Corral“B”. Evaluation of six risk factors for the development of bacteremia in children with cancer and febrile neutropenia. Guatemala J Haematol 2–40 zona 2.
Katsimpardi K, Papadakis V, Pangalis A, Parcharidou A, Panagiotou JP, Soutis M, et al. Infections in a pediatric patient cohort with acute lymphoblastic leukemia during the entire course of treatment. Support Care Cancer. 2006;14(3):277. 84.
Aslıhan Demire, Fehmi Tabak et al Secondary Infections in Febrile Neutropenia inHematological Malignancies İstanbul University Cerrahpaşa Faculty of Medicine: Indian J Med Microbiol. 2009 Oct-Dec;27(4):373-4.
Akova M, et al. Mangmenet of febrile patients with cancer .Clin Infect Dis. 40 (2), 239-24 M Akova et al. Clin Infect Dis. Dec20. 2004;40(2):239-245.
Gul N, Ozdemir G, Tuysuz H, Apak et al. Febrile neutropenia in children with acute lymphoblastic leukemia treated with BFM protocols blood. 2014;124(21):5245.
Phillips B, Selwood K, Lane SM, Skinner R, Gibson F, Chisholm JC, et al. Variation in policies for the management of febrile neutropenia in United Kingdom Children's Cancer Study Group centres. Arch Dis Child. 2007;92(6):495-8.
Feld R. Bloodstream infections in cancer patients with febrile neutropenia. Int J Antimicrob Agents. 2008;32(suppl 1):S30–3.
Pizzo PA, Ladisch S, Ribichaud K. Treatment of gram-positive, septicemia in cancer patients. Cancer. 1980;45:206-207.
Verhoef, J., Prevention of infections in the neutropenic patient. Clin Infect Dis. 1993; 17(Suppl 2):S359-67.
Klastersky J, Paesmans M, Institut Jules Bordet, Centre des Tumeurs de l'Universite Libre de Bruxelles. Risk-adapted strategy for the management of febrile neutropenia in cancer patients. Support Care Cancer. 2007;15(5):477-82.
Pizzo PA, Robichaud KJ, Wesley R, Commers JR. Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes. Medicine (Baltimore). 2012;61(3):153-65.
Pratupjai S. And Su-on Ch. Febrile neutropenia in children with acute leukemia. Department of Pediatrics, Khon Kaen Hospi. Khon Kaen Medical Journal. September - December 2009;33(3).
Karina P. Billote, Myrna T. Mendoza et al. Infections in Febrile Neutropenia and Possible Prognostic Factors Associated with Mortality'; Philippine. Phil J Microbiol Infect Dis. 2010;26(2):55-59.
Santolaya ME, Alvarez AM, Avilés CL, et al. Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. Clin Infect Dis. 20]02;35:678–83.
Hon KL, Leung CW, Cheng WT, Chan PK, Chu ,WC, Kwan YW, et al. Clinical presentations and outcome of severe febrile neutropenia Lancet. 2003; 361(9370):1701-3.
Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, et al. Incidence and Characteristics of bacterial infection in cancer patients. Emerg Infect Dis. 2009b;10(6):1095-101.
Joao Silva M, Ferraz C, Pissarra S, Cardoso MJ, Simoes J, Bonito Vitor A. Role of bacteria and atypical bacteria in ALL among children on chemotherapy Pediatr Infect Dis J. 2007;35(1):4-9.
Kempe A, Hall CB, MacDonald NE, Foye HR, Woodin KA, Cohen HJ, et al.bacterial infection in children with cancer. J Pediatr. 2009;115(1):33-9.
Kitanovski L, Jazbec J, Hojker S, Gubina M, Derganc M. Diagnostic accuracy of blood cultures for predicting bacteremia and clinical sepsis in febrile neutropenic children with cancer. Eur JClin Microbiol Infect Dis. 2006;25(6):413-5.
Philip A Pizzo. Drug Therapy Review Article. The New Eng J Med. 1993;328; 1323-32
Eduardo Velasco et al. Epidemiology of blood stream infections at a cancer. Sao Paulo Med J. 2000;118;5.
Stephen H Zinner. Changing Epidemiology of infections in patients with Neutropenia and Cancer: Emphasis on Gram-positive and Resistant Bacteria. Clin Inf Dis. 2006;29:490-4.
Koll BS, Brown AK. The changing epidemiology of infections at cancer hospitals. Clin Infect Dis. 1993;17(Suppl 2):S322-8.
Klastersky J, Paesmans M, Georgala A, Muanza;antibiotics for febrile neutropenic cancer patient using a score predictive for complications. J Clin Oncol. 2006;24(25):4129-34.
Johny AA, Clark A, Price N, Carrington D, Oakhill A, Marks DI. The use of antibiotics to treat of infection after induction phase of chemotherapy. 2002;29(2):113-5.
Freifeld AG, Martino P, Billingham L, et al. Antibacterial prophylaxis in patients with cancer and neutropenia. N Engl J Med. 2006;354(1):90,4.
Hughes W, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34(6):730-51.
Chamorey E, Magne N, Foa C, Otto J, Benard-Thiery I, Thyss A. Interscience Conference on Antimicrobial Agents and Chemotherapy. 2000;40:474.
Elting LS, Rubenstein EB, Rolston K, et al. Outcome, quality and cost of antibiotic therapy for febrile neutropenia. Journal of Clinical Oncology. 2000;18:3699-3706.
Pizzo PA, Rubin M, Freifeld A, Walsh TJ. The child with cancer and infection. I. Empiric therapy for fever and neutropenia, and preventive strategies. J Pediatr. 2010;119(5):679-94.
Pizzo P. Management of fever in patients with cancer and treatment induced neutropenia. N Engl J Med. 2012;328: 1323-32
Johnston E, et al., Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol. 2000;18(13): 2522-8.
Hodgson-Viden H, Grundy P, Robinson J. Early discontinuation of intravenous antimicrobial therapy in pediatric oncology patients with febrile neutropenia. Biomed Central Pediatrics. 2005;5:147-2431.
Yilmaz S, Oren H, Demircioğlu F, Irken G. Assessment of febrile neutropenia episodes in children with acute leukemia. Dokuz Eylül University, Faculty of Medicine, Izmir, Turkey. Int J. 2008; 32(suppl 1):S30–3.
Peng LH, Keng TC, Sinniah D. Fever in children with acute lymphoblastic leukemia. 1 February 1981;47(3):583–587.
Martina Söderman, Samuel Rhedin. Frequent Respiratory Viral Infections In Children With Febrile Neutropenia - aprospective follow-up study. Sweden. PLoS ONE. 11(6):e0157398.
Claire Ann B. Celiz-Pascual. MD Robert Dennis Garcia, infections in febrile neutropenic cancer patients who were undergoing chemotherapy at the Makati medical center. Makati Medical Philippines Center Pidsp Journal. 2011;12(1):165-71.
Bertone R, Candoni D, Russo M, Michieli D. Neutropenic patients with unexplained fever. La Sapienza University of Rome, Italy. Clin Infect Dis. 2003;17(Suppl 2):S378-84.
Pitiya R, Chusana S. Causative pathogens of fever in neutropenic patients at King Chulalongkorn Memorial Hospital. J Med Assoc Thai. 2010;93(7):776-83.
Hann I, Viscoli C, Paesmans M, Gaya H, Glauser M. A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies. International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC). Br J Haematol. 2012;99(3):580-8.
Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R, et al. 2011 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis. 2013;25(3):551- 73.
Viscoli C, Cometta A, Kern WV, Bock R, Paesmans M, Crokaert F, Glauser MP, Calandra T. International Antimicrobial Therapy Group of the European Organization for Research and Treatment of Cancer. Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients. Clin Microbiol Infect. 2006;12:212-216.
Thomas l. Robert phillips, Sarah alexander.et al. Neutropenia in children with malignanacy. Journal of Clinical Oncology. December 2012;30(35):4427-4438.
Olkinuora H, Rahiala J, Anttila VJ, Koskenvuo M, Vettenranta K. Immune deficiency and infections in children having cancer. .Article in Finnish Duodecim. 2013;129(12):1233-41.
Hadir M. Meir, MD, Ibrahim A. Balawi, MD, Hala M. Meer, MD, Hala Nayel, MD, Mohammad F. Al-Mobarak, MD. Fever and granulocytopenia in children with Acute Lymphoblastic Leukemia under induction therapy. Saudi Med J. 2001;22(5):423-427.
Zeina A. Kanafani Ghenwa K. Dakdouki Khalil I. El-Chammas Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon International Journal of Infectious Diseases September 2007;11(5)450–453.
Christina Orasch, Catherine Cordonnier, Murat Akova. European guideline for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance summary of the 2011 4th European Conference on Infections in Leukemia. J Pediatr Hematol Oncol. 2012;24(1):38-42.
Hyypiä T, Puhakka T, Ruuskanen O, Mäkelä M, Arola A, Arstila P. Infections in a pediatric patient cohort with acute lymphoblastic leukemia during consolidation. J Clin Microbiol. 2008; 36(7):2081-3.
Lie SO, Gustafsson G. Progress in the treatment of childhood leukaemias. Ann Med; 1992.
Minna Koskenvuoand Painosalama Oy. Febrile infections in children with leukemia, with special reference to respiratory viral infections Pediatrics Annales Universitatis Turkuensis, Medica-Odontologica. 2008; 18(13):2522-8.
Chong CY, Tan AM, Lou J. Infections in acute lymphoblastic leukaemia. Women’s and Children’s Hospital Ann Acad Med Singapore. 2008;27:491-5.
Bakhshi S1, Padmanjali KS, Arya LS. Infections in childhood acute lymphoblastic leukemia. New Delhi, India Pediatr Hematol Oncol. 2008 Jun;25(5):385.
Juan Enrique Corral“B”. Evaluation of six risk factors for the development of bacteremia in children with cancer and febrile neutropenia. Guatemala J Haematol 2–40 zona 2.
Katsimpardi K, Papadakis V, Pangalis A, Parcharidou A, Panagiotou JP, Soutis M, et al. Infections in a pediatric patient cohort with acute lymphoblastic leukemia during the entire course of treatment. Support Care Cancer. 2006;14(3):277. 84.
Aslıhan Demire, Fehmi Tabak et al Secondary Infections in Febrile Neutropenia inHematological Malignancies İstanbul University Cerrahpaşa Faculty of Medicine: Indian J Med Microbiol. 2009 Oct-Dec;27(4):373-4.
Akova M, et al. Mangmenet of febrile patients with cancer .Clin Infect Dis. 40 (2), 239-24 M Akova et al. Clin Infect Dis. Dec20. 2004;40(2):239-245.
Gul N, Ozdemir G, Tuysuz H, Apak et al. Febrile neutropenia in children with acute lymphoblastic leukemia treated with BFM protocols blood. 2014;124(21):5245.
Phillips B, Selwood K, Lane SM, Skinner R, Gibson F, Chisholm JC, et al. Variation in policies for the management of febrile neutropenia in United Kingdom Children's Cancer Study Group centres. Arch Dis Child. 2007;92(6):495-8.
Feld R. Bloodstream infections in cancer patients with febrile neutropenia. Int J Antimicrob Agents. 2008;32(suppl 1):S30–3.
Pizzo PA, Ladisch S, Ribichaud K. Treatment of gram-positive, septicemia in cancer patients. Cancer. 1980;45:206-207.
Verhoef, J., Prevention of infections in the neutropenic patient. Clin Infect Dis. 1993; 17(Suppl 2):S359-67.
Klastersky J, Paesmans M, Institut Jules Bordet, Centre des Tumeurs de l'Universite Libre de Bruxelles. Risk-adapted strategy for the management of febrile neutropenia in cancer patients. Support Care Cancer. 2007;15(5):477-82.
Pizzo PA, Robichaud KJ, Wesley R, Commers JR. Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes. Medicine (Baltimore). 2012;61(3):153-65.
Pratupjai S. And Su-on Ch. Febrile neutropenia in children with acute leukemia. Department of Pediatrics, Khon Kaen Hospi. Khon Kaen Medical Journal. September - December 2009;33(3).
Karina P. Billote, Myrna T. Mendoza et al. Infections in Febrile Neutropenia and Possible Prognostic Factors Associated with Mortality'; Philippine. Phil J Microbiol Infect Dis. 2010;26(2):55-59.
Santolaya ME, Alvarez AM, Avilés CL, et al. Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. Clin Infect Dis. 20]02;35:678–83.
Hon KL, Leung CW, Cheng WT, Chan PK, Chu ,WC, Kwan YW, et al. Clinical presentations and outcome of severe febrile neutropenia Lancet. 2003; 361(9370):1701-3.
Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, et al. Incidence and Characteristics of bacterial infection in cancer patients. Emerg Infect Dis. 2009b;10(6):1095-101.
Joao Silva M, Ferraz C, Pissarra S, Cardoso MJ, Simoes J, Bonito Vitor A. Role of bacteria and atypical bacteria in ALL among children on chemotherapy Pediatr Infect Dis J. 2007;35(1):4-9.
Kempe A, Hall CB, MacDonald NE, Foye HR, Woodin KA, Cohen HJ, et al.bacterial infection in children with cancer. J Pediatr. 2009;115(1):33-9.
Kitanovski L, Jazbec J, Hojker S, Gubina M, Derganc M. Diagnostic accuracy of blood cultures for predicting bacteremia and clinical sepsis in febrile neutropenic children with cancer. Eur JClin Microbiol Infect Dis. 2006;25(6):413-5.
Philip A Pizzo. Drug Therapy Review Article. The New Eng J Med. 1993;328; 1323-32
Eduardo Velasco et al. Epidemiology of blood stream infections at a cancer. Sao Paulo Med J. 2000;118;5.
Stephen H Zinner. Changing Epidemiology of infections in patients with Neutropenia and Cancer: Emphasis on Gram-positive and Resistant Bacteria. Clin Inf Dis. 2006;29:490-4.
Koll BS, Brown AK. The changing epidemiology of infections at cancer hospitals. Clin Infect Dis. 1993;17(Suppl 2):S322-8.
Klastersky J, Paesmans M, Georgala A, Muanza;antibiotics for febrile neutropenic cancer patient using a score predictive for complications. J Clin Oncol. 2006;24(25):4129-34.
Johny AA, Clark A, Price N, Carrington D, Oakhill A, Marks DI. The use of antibiotics to treat of infection after induction phase of chemotherapy. 2002;29(2):113-5.
Freifeld AG, Martino P, Billingham L, et al. Antibacterial prophylaxis in patients with cancer and neutropenia. N Engl J Med. 2006;354(1):90,4.
Hughes W, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34(6):730-51.
Chamorey E, Magne N, Foa C, Otto J, Benard-Thiery I, Thyss A. Interscience Conference on Antimicrobial Agents and Chemotherapy. 2000;40:474.
Elting LS, Rubenstein EB, Rolston K, et al. Outcome, quality and cost of antibiotic therapy for febrile neutropenia. Journal of Clinical Oncology. 2000;18:3699-3706.
Pizzo PA, Rubin M, Freifeld A, Walsh TJ. The child with cancer and infection. I. Empiric therapy for fever and neutropenia, and preventive strategies. J Pediatr. 2010;119(5):679-94.
Pizzo P. Management of fever in patients with cancer and treatment induced neutropenia. N Engl J Med. 2012;328: 1323-32
Johnston E, et al., Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol. 2000;18(13): 2522-8.
Hodgson-Viden H, Grundy P, Robinson J. Early discontinuation of intravenous antimicrobial therapy in pediatric oncology patients with febrile neutropenia. Biomed Central Pediatrics. 2005;5:147-2431.
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