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Infectious complications in patients with acute promyelocytic leukaemia treated with the AIDA regimen

Abstract

Infections represent a frequent complication of chemotherapy used for acute myeloid leukaemia (AML) and are associated with important toxicity frequently leading to treatment discontinuation. Acute promyelocytic leukaemia (APL) is a unique AML subset requiring tailored therapy including all-trans retinoic acid and anthracycline-based chemotherapy. We analysed in this study the incidence and type of infections complicating the clinical course of 89 consecutive APL patients receiving the AIDA protocol at a single institution. A total of 179 febrile episodes were registered during induction and consolidation, 52% of which were of unknown origin. Infections were clinically and microbiologically documented in 10.6 and 37.4% of cases, respectively. Coagulase-negative staphylococci represented the major cause of septicaemia (28%) and were more frequently isolated during induction, whereas viridans group streptococci, the second pathogen most frequently isolated from blood (27%), represented the principal pathogen detected during consolidation and were significantly associated with mucositis. Gram-negative bacteria accounted for 33.3% of all blood isolates. Fungal infections were only occasionally observed. Bloodstream infections in APL patients were compared with those documented in 271 consecutive patients affected by other subtypes of AML. The incidence of total septicaemia episodes, of staphylococcal bacteraemias and of fungaemias was significantly higher in patients with other AMLs. Empirical antibiotic therapy with ceftriaxone plus amikacin was effective in 73% of APL cases, most of the remaining cases being successfully managed by the addition of teicoplanin. One single death apparently related to infectious complication was recorded. Overall, infections led to antileukaemic treatment withdrawal in six patients, five of whom currently remain in haematologic remission for 13–106 months. These results indicate that a particular pattern of infections is observed in APL patients receiving ATRA plus anthracycline-based chemotherapy and that these appear to be effectively counteracted by standard management.

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Georg Maschmeyer, Lars Bullinger, … Thierry Calandra

References

  1. Fenaux P, Chomienne C, Degos L . All trans retinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia. Semin Hematol 2001; 38: 13–25.

    Article  CAS  PubMed  Google Scholar 

  2. Asou N, Adachi J, Tamura J, Kanamaru A, Kageyama S, Hiraoka A et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. J Clin Oncol 1998; 16: 78–85.

    Article  CAS  PubMed  Google Scholar 

  3. Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH . Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood 1999; 93: 4131–4143.

    CAS  PubMed  Google Scholar 

  4. Estey E, Thall PF, Pierce S, Kantajian H, Keating M . Treament of newly diagnosed acute promyelocytic leukemia without cytarabine. J Clin Oncol 1997; 15: 483–490.

    Article  CAS  PubMed  Google Scholar 

  5. Fenaux P, Chastang C, Chevret S, Sanz MA, Dompret H, Archimbaud E et al. A randomized comparison of all-trans retinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy, and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood 1999; 94: 1192–1200.

    CAS  PubMed  Google Scholar 

  6. Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H et al. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. Leukemia 2000; 14: 1362–1370.

    Article  CAS  PubMed  Google Scholar 

  7. Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C et al. Molecular remission in PML/RARα-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood 1997; 90: 1014–1021.

    CAS  PubMed  Google Scholar 

  8. Sanz MA, Martín G, Rayón C, Esteve J, Gonzalez M, Diaz-Mediavilla J et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARa-positive acute promyelocytic leukemia. Blood 1999; 94: 3015–3021.

    CAS  PubMed  Google Scholar 

  9. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337: 1021–1028.

    Article  CAS  PubMed  Google Scholar 

  10. Grimwade D . The pathogenesis of acute promyelocytic leukemia: evaluation of the role of molecular diagnosis and monitoring in the management of the disease. Br J Haematol 1999; 106: 591–613.

    Article  CAS  PubMed  Google Scholar 

  11. Lo Coco F, Diverio D, Falini B, Biondi A, Nervi C, Pelicci PG . Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood 1999; 94: 12–22.

    PubMed  Google Scholar 

  12. Estey EH, Giles FJ, Kantarjian H, O'Brien S, Cortes J, Freireich EJ, Lopez-Berestein G, Keating M . Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia. Blood 1999; 94: 2230–2235.

    CAS  PubMed  Google Scholar 

  13. Lo Coco F, Diverio D, Pandolfi PP, Biondi A, Rossi V, Avvisati G et al. Molecular evaluation of residual disease as a predictor of relapse in acute promyelocytic leukemia. Lancet 1992; 340: 1437–1438.

    Article  CAS  PubMed  Google Scholar 

  14. Girmenia C, Latagliata R, Tosti S, Morano SG, Celesti F, Coppola L et al. Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy. Leukemia 1999; 13: 514–517.

    Article  CAS  PubMed  Google Scholar 

  15. Girmenia C, Alimena G, Latagliata R, Morano SG, Celesti F, Coppola L et al. Out-patient management of acute myeloid leukemia after consolidation chemotherapy. Role of a hematologic emergency unit. Haematologica 1999; 84: 814–819.

    CAS  PubMed  Google Scholar 

  16. Keating S, Suciu S, Mandelli F, De Witte T, Willemze R, Archimbaud E et al. Autologous BMT or PSCT for patients with AML in first CR: a preliminary analysis of the AML 10 study of the leukemia cooperative group (LCG) of the EORTC and GIMEMA. Blood 1997; 90 (Suppl. 1): 235a.

    Google Scholar 

  17. Archimbaud E, Jehn U, Thomas X, De Cataldo F, Fillet G, Belhabri A et al. Idarubicin vs mitoxantrone in association with VP-16 and Ara-c for induction/consolidation therapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia (AML). Final analysis of a randomized trial. Proceedings of the 33rd ASCO Annual Meeting 1997; 16: 3a (Abstract 7).

  18. Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell Jr RO . The ‘retinoic acid syndrome’ in acute promyelocytic leukemia. Ann Intern Med 1992; 117: 292–296.

    Article  CAS  PubMed  Google Scholar 

  19. de Button S, Chevret S, Coiteux V, Dombret, H, Sanz M, San Miguel J et al. Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukaemia (APL) with low white blood cell counts: results from APL 93 trial. Leukemia 2003; 17: 339–342.

    Article  Google Scholar 

  20. Bochud PY, Egglman P, Calandra T, Van Melle G, Saghafi G, Francioli P . Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis 1994; 18: 25–31.

    Article  CAS  PubMed  Google Scholar 

  21. Richard P, Del Valle GA, Moreau P, Milpied N, Felice MP, Daeschler T et al. Viridans streptococcal bacteraemia in patients with neutropenia. Lancet 1995; 345: 1607–1609.

    Article  CAS  PubMed  Google Scholar 

  22. Valteau D, Hartmann O, Brugieres L, Vassal G, Benhamou E, Andremont A et al. Streptococcal septicaemia following autologous bone marrow transplantation in children treated with high-dose chemotherapy. Bone Marrow Transplant 1991; 7: 415–419.

    CAS  PubMed  Google Scholar 

  23. Cohen J, Donnelly JP, Worsley AM, Catovsky D, Goldman JM, Galton DAG . Septicemia caused by viridans streptococci in neutropenic patients with leukaemia. Lancet 1983; ii: 1452–1454.

    Article  Google Scholar 

  24. Classen DC, Burke JP, Ford CD, Evershed S, Aloia MR, Wilfahrt JK et al. Streptococcus mitis sepsis in bone marrow transplant patients receiving oral antimicrobial prophylaxis. Am J Med 1990; 89: 441–446.

    Article  CAS  PubMed  Google Scholar 

  25. Elting LS, Bodey GP, Keefe BH . Septicemia and shock syndrome due to viridans streptococci: a case–control study of predisposing factors. Clin Infect Dis 1994; 14: 1201–1207.

    Article  Google Scholar 

  26. Sanz MA, Lo Coco F, Martin G, Avvisati G, Rayon C, Barbui T et al. Definition of relapse risk and role of non-anthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood 2000; 96: 1247–1253.

    CAS  PubMed  Google Scholar 

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Girmenia, C., Lo Coco, F., Breccia, M. et al. Infectious complications in patients with acute promyelocytic leukaemia treated with the AIDA regimen. Leukemia 17, 925–930 (2003). https://doi.org/10.1038/sj.leu.2402899

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