Vol 52, No 6 (2021)
Guidelines / Expert consensus
Published online: 2021-10-11

open access

Page views 7782
Article views/downloads 1196
Get Citation

Connect on Social Media

Connect on Social Media

Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations

Jan Styczynski1, Agnieszka Piekarska2, Agnieszka Zaucha-Prażmo3, Jan Maciej Zaucha2, Olga Zając-Spychała4, Tomasz Wróbel5, Agnieszka Wierzbowska6, Adam Walter-Croneck7, Jacek Wachowiak4, Marek Ussowicz8, Tomasz Szczepański9, Agnieszka Sobkowiak-Sobierajska4, Małgorzata Sobczyk-Kruszelnicka10, Katarzyna Smalisz11, Mariola Sędzimirska12, Piotr Rzepecki13, Beata Piątkowska-Jakubas14, Anna Łojko15, Ewa Lutwin16, Ewa Lech-Marańda17, Bogusław Machaliński18, Aleksandra Krasowska-Kwiecień19, Krzysztof Kałwak8, Marek Hus7, Iwona Hus17, Grzegorz Helbig20, Dorota Hawrylecka21, Kazimierz Hałaburda17, Jolanta Goździk19, Sebastian Giebel10, Adam Fronczak6, Jarosław Dybko12, Agnieszka Druzd-Sitek22, Katarzyna Drabko3, Krzysztof Czyżewski1, Anna Czyż5, Edyta Cichocka23, Piotr Boguradzki24, Maria Bieniaszewska2, Bartłomiej Baumert18, Grzegorz Basak24, Lidia Gil15
Acta Haematol Pol 2021;52(6):528-542.

Abstract

Infections are still a major reason of morbidity and one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper is presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation of Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing ECIL (European Conference on Infections in Leukemia) and EBMT (European Society of Blood and Marrow Transplantation) guidelines, as well as results of survey performed among all Polish transplant centers, were the background material for working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

Article available in PDF format

View PDF Download PDF file

References

  1. Styczyński J, Tridello G, Koster L, et al. Infectious Diseases Working Party EBMT. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020; 55(1): 126–136.
  2. Groll A, Pana D, Lanternier F, et al. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021; 22(6): e254–e269.
  3. Lehrnbecher T, Averbuch D, Castagnola E, et al. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation. The Lancet Oncol. 2021; 22(6): e270–e280.
  4. 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(8): e260–e272.
  5. Ward KN, Hill JA, Hubacek P, et al. 2017 European Conference on Infections in Leukaemia (ECIL). Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation. Haematologica. 2019; 104(11): 2155–2163.
  6. Styczynski J, van der Velden W, Fox CP, et al. Sixth European Conference on Infections in Leukemia, a joint venture of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (EBMT-IDWP), the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer (EORTC-IDG), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN). Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016; 101(7): 803–811.
  7. Cesaro S, Dalianis T, Hanssen Rinaldo C, et al. ECIL-6 Group. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018; 73(1): 12–21.
  8. Maertens J, Cesaro S, Maschmeyer G, et al. 5th European Conference on Infections in Leukaemia (ECIL-5), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organisation for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and the European LeukemiaNet (ELN). ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016; 71(9): 2397–2404.
  9. Averbuch D, Cordonnier C, Livermore DM, et al. ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011). Haematologica. 2013; 98(12): 1836–1847.
  10. Averbuch D, Orasch C, Cordonnier C, et al. ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. European guidelines 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. Haematologica. 2013; 98(12): 1826–1835.
  11. Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017; 102(3): 433–444.
  12. Hirsch HH, Martino R, Ward KN, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis. 2013; 56(2): 258–266.
  13. Styczynski J, Reusser P, Einsele H, et al. Second European Conference on Infections in Leukemia. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009; 43(10): 757–770.
  14. Matthes-Martin S, Feuchtinger T, Shaw PJ, et al. Fourth European Conference on Infections in Leukemia. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 (2011). Transpl Infect Dis. 2012; 14(6): 555–563.
  15. Engelhard D, Mohty B, de la Camara R, et al. European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: summary of ECIL-4 (2011), on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN. Transpl Infect Dis. 2013; 15(3): 219–232.
  16. Maertens JA, Girmenia C, Brüggemann RJ, et al. European Conference on Infections in Leukaemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and, European Conference on Infections in Leukaemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and the European LeukemiaNet (ELN). European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia. J Antimicrob Chemother. 2018; 73(12): 3221–3230.
  17. Styczyński J, Czyżewski K, Ussowicz M, et al. Antimicrobial prophylaxis in patients after hematopoietic cell transplantation: results of a survey of the Polish Federation of Bone Marrow Transplant Centers. Acta Haematol Pol. 2020; 51(3): 183–186.
  18. Styczyński J, Czyżewski K, Ussowicz M, et al. Antimicrobial prophylaxis in patients after hematopoietic cell transplantation: results of a survey of the Polish Federation of Bone Marrow Transplant Centers. Acta Haematol Pol. 2020; 51(3): 183–186.
  19. Taplitz RA, Kennedy EB, Bow EJ, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update summary. J Oncol Pract. 2018; 14(11): 692–695.
  20. Carreras E, Dufour C, Mohty M, Kröger N. The EBMT Handbook: hematopoietic stem cell transplantation and cellular therapies. Springer, Cham 2019.
  21. Czyżewski K, Styczyński J, Giebel S, et al. for Polish Society of Pediatric Oncology and Hematology and Polish Society of Hematology and Blood Transfusion. Age-dependent determinants of infectious complications profile in children and adults after hematopoietic cell transplantation: lesson from the nationwide study. Ann Hematol. 2019; 98(9): 2197–2211.
  22. Mikulska M, Averbuch D, Tissot F, et al. European Conference on Infections in Leukemia (ECIL). Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018; 76(1): 20–37.
  23. Egan G, Robinson PD, Martinez JPD, et al. Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials. Cancer Med. 2019; 8(10): 4536–4546.
  24. European Centre for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe — annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2017. ECDC, Stockholm 2018.
  25. Davies JM, Lewis MPN, Wimperis J, et al. British Committee for Standards in Haematology. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a working party of the Haemato-Oncology task force. Br J Haematol. 2011; 155(3): 308–317.
  26. Zając-Spychała O, Wachowiak J, Frączkiewicz J, et al. Multidrug-resistant bacterial infections in children undergoing haematopoietic stem cell transplantation over a 6-year period: analysis of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation. J Appl Microbiol. 2020; 128(1): 292–300.
  27. Zając-Spychała O, Wachowiak J, Pieczonka A, et al. Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation. Transpl Infect Dis. 2016; 18(5): 690–698.
  28. Alexander S, Fisher BT, Gaur AH, et al. Children’s Oncology Group. Effect of levofloxacin prophylaxis on bacteremia in children with acute leukemia or undergoing hematopoietic stem cell transplantation: a randomized clinical trial. JAMA. 2018; 320(10): 995–1004.
  29. Tandan M, Cormican M, Vellinga A. Adverse events of fluoroquinolones vs. other antimicrobials prescribed in primary care: A systematic review and meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2018; 52(5): 529–540.
  30. Lehrnbecher T, Fisher BT, Phillips B, et al. Guideline for antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation. Clin Infect Dis. 2020; 71(1): 226–236.
  31. Gil L, Kałwak K, Piekarska A, et al. Antifungal management in adults and children with hematological malignancies or undergoing hematopoietic cell transplantation: recommendations of Polish Society of Hematology and Blood Transfusion, Polish Society of Pediatric Oncology and Hematology, and Polish Adult Leukemia Study Group, 2020. Acta Haematologica Polonica. 2020; 51(2): 60–72.
  32. Jantunen E, Salonen J, Juvonen E, et al. Invasive fungal infections in autologous stem cell transplant recipients: a nation-wide study of 1188 transplanted patients. Eur J Haematol. 2004; 73(3): 174–178.
  33. Girmenia C, Raiola AM, Piciocchi A, et al. Primary prophylaxis of invasive fungal diseases in allogeneic stem cell transplantation: revised recommendations from a consensus process by Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014; 20(8): 1080–1088.
  34. Blennow O, Remberger M, Törlén J, et al. Risk factors for invasive mold infections and implications for choice of prophylaxis after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2016; 22(9): 1684–1689.
  35. van Burik JAH, Ratanatharathorn V, Stepan DE, et al. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. 2004; 39(10): 1407–1416.
  36. Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007; 356(4): 335–347.
  37. Stern A, Su Y, Lee YJ, et al. A single-center, open-label trial of isavuconazole prophylaxis against invasive fungal infection in patients undergoing allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2020; 26(6): 1195–1202.
  38. Fontana L, Perlin DS, Zhao Y, et al. Isavuconazole prophylaxis in patients with hematologic malignancies and hematopoietic cell transplant recipients. Clin Infect Dis. 2020; 70(5): 723–730.
  39. Welzen MEB, Brüggemann RJM, Van Den Berg JM, et al. A twice daily posaconazole dosing algorithm for children with chronic granulomatous disease. Pediatr Infect Dis J. 2011; 30(9): 794–797.
  40. Arrieta AC, Sung L, Bradley JS, et al. A non-randomized trial to assess the safety, tolerability, and pharmacokinetics of posaconazole oral suspension in immunocompromised children with neutropenia. PLoS One. 2019; 14(3): e0212837.
  41. Styczyński J. ABC of viral infections in hematology: focus on herpesviruses. Acta Haematol Pol. 2019; 50(3): 159–166.
  42. Prentice HG, Gluckman E, Powles RL, et al. Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group. Lancet. 1994; 343(8900): 749–753.
  43. Ljungman P, de La Camara R, Milpied N, et al. Valacyclovir International Bone Marrow Transplant Study Group. Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants. Blood. 2002; 99(8): 3050–3056.
  44. Marty FM, Ljungman PT, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017; 377(25): 2433–2444.
  45. Ljungman P, Larsson K, Kumlien G, et al. Leukocyte depleted, unscreened blood products give a low risk for CMV infection and disease in CMV seronegative allogeneic stem cell transplant recipients with seronegative stem cell donors. Scand J Infect Dis. 2002; 34(5): 347–350.
  46. Nichols WG, Price TH, Gooley T, et al. Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood. 2003; 101(10): 4195–4200.
  47. Winston DJ, Yeager AM, Chandrasekar PH, et al. Valacyclovir Cytomegalovirus Study Group. Randomized comparison of oral valacyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation. Clin Infect Dis. 2003; 36(6): 749–758.
  48. Winston DJ, Ho WG, Bartoni K, et al. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial. Ann Intern Med. 1993; 118(3): 179–184.
  49. Goodrich JM, Bowden RA, Fisher L, et al. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med. 1993; 118(3): 173–178.
  50. Reusser P, Einsele H, Lee J, et al. Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002; 99(4): 1159–1164.
  51. Styczyński J, Tridello G, Xhaard A, et al. Use of letermovir in off-label indications: Infectious Diseases Working Party of European Society of Blood and Marrow Transplantation retrospective study. Bone Marrow Transplant. 2021; 56(5): 1171–1179.
  52. Styczyński J, Czyżewski K, Dębski R. Primary prophylaxis with letermovir for prevention of CMV infection in two children. Acta Haematol Pol. 2020; 51(4): 263–264.
  53. Raanani P, Gafter-Gvili A, Paul M, et al. Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2009; 27(5): 770–781.
  54. Cesaro S, Pegoraro A, Tridello G, et al. A prospective study on modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation. Transplantation. 2010; 89(12): 1533–1540.
  55. Muramatsu H, Takahashi Y, Shimoyama Y, et al. CD20-negative Epstein-Barr virus-associated post-transplant lymphoproliferative disease refractory to rituximab in a patient with severe aplastic anemia. Int J Hematol. 2011; 93(6): 779–781.
  56. Worth A, Conyers R, Cohen J, et al. Pre-emptive rituximab based on viraemia and T cell reconstitution: a highly effective strategy for the prevention of Epstein-Barr virus-associated lymphoproliferative disease following stem cell transplantation. Br J Haematol. 2011; 155(3): 377–385.
  57. Barker JN, Doubrovina E, Sauter C, et al. Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood. 2010; 116(23): 5045–5049.
  58. Doubrovina E, Oflaz-Sozmen B, Prockop SE, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012; 119(11): 2644–2656.
  59. Czyzewski K, Dziedzic M, Salamonowicz M, et al. Epidemiology, outcome and risk factors analysis of viral infections in children and adolescents undergoing hematopoietic cell transplantation: antiviral drugs do not prevent Epstein-Barr virus reactivation. Infect Drug Resist. 2019; 12: 3893–3902.
  60. Ljungman P, Styczynski J, Einsele H. Viral infections. In: Carreras E, Dufour C, Mohty M, Kroger N. ed. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Spiringer, Cham 2019: 281–290.
  61. Hadjibabaie M, Alimoghaddam K, Shamshiri AR, et al. Continuous bladder irrigation prevents hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. Urol Oncol. 2008; 26(1): 43–46.
  62. Leung AYH, Chan MTL, Yuen KY, et al. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2005; 40(4): 528–537.
  63. Miller AN, Glode A, Hogan KR, et al. Efficacy and safety of ciprofloxacin for prophylaxis of polyomavirus BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2011; 17(8): 1176–1181.
  64. Ogata M, Satou T, Kadota Ji, et al. Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study. Clin Infect Dis. 2013; 57(5): 671–681.
  65. Ljungman P, Mikulska M, de la Camara R, et al. European Society for Blood and Marrow Transplantation, European Society for Blood and Marrow Transplantation. The challenge of COVID-19 and hematopoietic cell transplantation; EBMT recommendations for management of hematopoietic cell transplant recipients, their donors, and patients undergoing CAR T-cell therapy. Bone Marrow Transplant. 2020; 55(11): 2071–2076.
  66. Ljungman P, de la Camara R, Mikulska M, et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia. 2021; 35(10): 2885–2894.
  67. Ljungman P, Cesaro S, Cordonnier C, Mikulska M, Styczynski J, de la Camara R. COVID-19 vaccines. EBMT recommendations. . https://www.ebmt.org/ (September 5, 2021).
  68. Martino R. Other life-threatening infections. In: Carreras E, Dufour C, Mohty M, Kroger N. ed. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Springer, Cham 2019: 291–299.
  69. Tomblyn M, Chiller T, Einsele H, et al. Center for International Blood and Marrow Research, National Marrow Donor program, European Blood and MarrowTransplant Group, American Society of Blood and Marrow Transplantation, Canadian Blood and Marrow Transplant Group, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Association of Medical Microbiology and Infectious Disease Canada, Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15(10): 1143–1238.
  70. Styczynski J, Tridello G, Donnelly JP, et al. Protective environment for hematopoietic cell transplant (HSCT) recipients: The Infectious Diseases Working Party EBMT analysis of global recommendations on health-care facilities. Bone Marrow Transplant. 2018; 53(9): 1131–1138.
  71. Ifversen M, Meisel R, Sedlacek P, et al. Supportive care during pediatric hematopoietic stem cell transplantation: prevention of infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT). Front Pediatr. 2021; 9: 705179.