Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine

Retrospective analysis of 224 cases

Michele Malagola, Annalisa Peli, Daniela Damiani, Anna Candoni, Mario Tiribelli, Giovanni Martinelli, Pier Paolo Piccaluga, Stefania Paolini, Francesco De Rosa, Francesco Lauria, Monica Bocchia, Marco Gobbi, Ivana Pierri, Alfonso Zaccaria, Eliana Zuffa, Patrizio Mazza, Giancarla Priccolo, Luigi Gugliotta, Alessandro Bonini, Giuseppe Visani & 7 others Cristina Skert, Cesare Bergonzi, Aldo Maria Roccaro, Carla Filì, Renato Fanin, Michele Baccarani, Domenico Russo

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients ≤65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.

Original languageEnglish
Pages (from-to)354-363
Number of pages10
JournalEuropean Journal of Haematology
Volume81
Issue number5
DOIs
Publication statusPublished - Nov 2008

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Mycoses
Bacterial Infections
Acute Myeloid Leukemia
Incidence
Bacteremia
Infection
Induction Chemotherapy
Fever
Idarubicin
fludarabine
Cytosine
Opportunistic Infections
Etoposide
Virus Diseases
Leukemia
Morbidity
Recurrence
Drug Therapy
Mortality
Invasive Fungal Infections

Keywords

  • Acute leukaemia
  • Fever
  • Fludarabine
  • Induction
  • Infections

ASJC Scopus subject areas

  • Hematology

Cite this

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine : Retrospective analysis of 224 cases. / Malagola, Michele; Peli, Annalisa; Damiani, Daniela; Candoni, Anna; Tiribelli, Mario; Martinelli, Giovanni; Piccaluga, Pier Paolo; Paolini, Stefania; De Rosa, Francesco; Lauria, Francesco; Bocchia, Monica; Gobbi, Marco; Pierri, Ivana; Zaccaria, Alfonso; Zuffa, Eliana; Mazza, Patrizio; Priccolo, Giancarla; Gugliotta, Luigi; Bonini, Alessandro; Visani, Giuseppe; Skert, Cristina; Bergonzi, Cesare; Roccaro, Aldo Maria; Filì, Carla; Fanin, Renato; Baccarani, Michele; Russo, Domenico.

In: European Journal of Haematology, Vol. 81, No. 5, 11.2008, p. 354-363.

Research output: Contribution to journalArticle

Malagola, M, Peli, A, Damiani, D, Candoni, A, Tiribelli, M, Martinelli, G, Piccaluga, PP, Paolini, S, De Rosa, F, Lauria, F, Bocchia, M, Gobbi, M, Pierri, I, Zaccaria, A, Zuffa, E, Mazza, P, Priccolo, G, Gugliotta, L, Bonini, A, Visani, G, Skert, C, Bergonzi, C, Roccaro, AM, Filì, C, Fanin, R, Baccarani, M & Russo, D 2008, 'Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: Retrospective analysis of 224 cases', European Journal of Haematology, vol. 81, no. 5, pp. 354-363. https://doi.org/10.1111/j.1600-0609.2008.01122.x
Malagola, Michele ; Peli, Annalisa ; Damiani, Daniela ; Candoni, Anna ; Tiribelli, Mario ; Martinelli, Giovanni ; Piccaluga, Pier Paolo ; Paolini, Stefania ; De Rosa, Francesco ; Lauria, Francesco ; Bocchia, Monica ; Gobbi, Marco ; Pierri, Ivana ; Zaccaria, Alfonso ; Zuffa, Eliana ; Mazza, Patrizio ; Priccolo, Giancarla ; Gugliotta, Luigi ; Bonini, Alessandro ; Visani, Giuseppe ; Skert, Cristina ; Bergonzi, Cesare ; Roccaro, Aldo Maria ; Filì, Carla ; Fanin, Renato ; Baccarani, Michele ; Russo, Domenico. / Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine : Retrospective analysis of 224 cases. In: European Journal of Haematology. 2008 ; Vol. 81, No. 5. pp. 354-363.
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abstract = "Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients ≤65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). Results: During the induction phase, 146 (65{\%}) patients experienced fever of undetermined origin (FUO), 30 (13{\%}) and 47 (21{\%}) patients had Gram-negative and positive bacteremias, respectively, and 10 (4{\%}) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10{\%}, 8{\%} and 60{\%} respectively. During consolidation, 75 (35{\%}) patients had FUO, 43 (20{\%}) and 40 (19{\%}) patients had Gram-negative and positive bacteremias, respectively, and 5 (2{\%}) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14{\%}, 5{\%} and 80{\%} respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38{\%} and the incidence of probable/proven IFIs during the induction/consolidation programme was 7{\%}. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.",
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TY - JOUR

T1 - Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine

T2 - Retrospective analysis of 224 cases

AU - Malagola, Michele

AU - Peli, Annalisa

AU - Damiani, Daniela

AU - Candoni, Anna

AU - Tiribelli, Mario

AU - Martinelli, Giovanni

AU - Piccaluga, Pier Paolo

AU - Paolini, Stefania

AU - De Rosa, Francesco

AU - Lauria, Francesco

AU - Bocchia, Monica

AU - Gobbi, Marco

AU - Pierri, Ivana

AU - Zaccaria, Alfonso

AU - Zuffa, Eliana

AU - Mazza, Patrizio

AU - Priccolo, Giancarla

AU - Gugliotta, Luigi

AU - Bonini, Alessandro

AU - Visani, Giuseppe

AU - Skert, Cristina

AU - Bergonzi, Cesare

AU - Roccaro, Aldo Maria

AU - Filì, Carla

AU - Fanin, Renato

AU - Baccarani, Michele

AU - Russo, Domenico

PY - 2008/11

Y1 - 2008/11

N2 - Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients ≤65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.

AB - Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients ≤65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.

KW - Acute leukaemia

KW - Fever

KW - Fludarabine

KW - Induction

KW - Infections

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DO - 10.1111/j.1600-0609.2008.01122.x

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EP - 363

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