Infektionen bei Patient*innen mit Akuter Myeloischer Leukämie

Eine der häufigsten Komplikationen während der Therapie der Akuten Myeloischen Leukämie (AML) sind Infektionen. Die lange Chemotherapie-assoziierte Neutropeniephase begünstigt neben bakteriellen und viralen Infektionen insbesondere das Auftreten von Pilzinfektionen. Da Infektionen mit einer erhöhten Morbidität und Mortalität verbunden sind, spielen eine umgehende Diagnostik und Therapie sowie die medikamentöse Prophylaxe eine wichtige Rolle.

Abstract

Infections represent one of the most frequent complications during therapy of acute myeloid leukemia (AML). In addition to associated prolonged phases of neutropenia, damage to the mucosal barrier by cytotoxic agents favors infections caused by endogenous pathogens. The source often remains unknown with bacteremia being the most common evidence of infection. Infections with gram-positive bacteria predominate, however, infections with gram-negative bacteria more often lead to sepsis and death. Due to prolonged neutropenia, patients with AML are furthermore at risk for invasive fungal infections. Viruses, on the other hand, are rarely the cause of neutropenic fever. Because of the limited inflammatory response in neutropenic patients, fever is often the only sign of infection and therefore always represents a hematologic emergency. Prompt diagnosis and initiation of an adequate anti-infective therapy are critical to avoid progression to sepsis and possibly death.

Kernaussagen

• Infektionen sind aufgrund der lang andauernden Neutropeniephasen während der Induktions- und Postremissionstherapien eine häufige und oft lebensbedrohliche Komplikation.

• Neutropenisches Fieber kann das einzige Zeichen einer schweren Infektion sein und stellt daher immer einen onkologischen Notfall dar.

• Der Auslöser einer Infektion bleibt oft unklar, jedoch müssen neben bakteriellen Infektionen außerdem invasive Pilzinfektionen bei der spezifischen Diagnostik und Auswahl der antimikrobiellen Therapie berücksichtigt werden.

• Zur effektiven Infektionsprophylaxe kommen Antibiotika, Virostatika und Antimykotika zum Einsatz.

• Die Einnahme prophylaktischer Azol-Antimykotika erfordert die engmaschige Überwachung möglicher Interaktionen und in einigen Fällen die Dosisanpassung neuer molekular zielgerichteter AML-Therapeutika.

Schlüsselwörter

akute myeloische Leukämie - neutropenisches Fieber - invasive Mykose

Keywords

acute myeloid leukemia - neutropenic fever - invasive fungal disease

Publication History

Article published online:
29 March 2023

• Literatur

• 1 Heinz WJ, Buchheidt D, Christopeit M. et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol 2017; 96 (11) 1775-1792 DOI: 10.1007/s00277-017-3098-3. (PMID: 28856437)
• 2 Flowers CR, Seidenfeld J, Bow EJ. et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2013; 31 (06) 794-810 DOI: 10.1200/JCO.2012.45.8661. (PMID: 23319691)
• 3 Kern WV, Marchetti O, Drgona L. et al. Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, randomized, multicenter trial comparing single daily moxifloxacin with twice daily ciprofloxacin plus amoxicillin/clavulanic acid combination therapy--EORTC infectious diseases group trial XV. J Clin Oncol 2013; 31 (09) 1149-1156
• 4 Pagano L, Caira M, Nosari A. et al. Etiology of febrile episodes in patients with acute myeloid leukemia: results from the Hema e-Chart Registry. Arch Intern Med 2011; 171 (16) 1502-1503
• 5 Hämäläinen S, Kuittinen T, Matinlauri I. et al. Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: Causes and consequences. Leuk Lymphoma 2008; 49 (03) 495-501 DOI: 10.1080/10428190701809172. (PMID: 18297526)
• 6 Nesher L. Rolston KV. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection 2014; 42 (01) 5-13 DOI: 10.1007/s15010-013-0525-9. (PMID: 23975584)
• 7 Averbuch D, Orasch C, Cordonnier C. et al. 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 DOI: 10.3324/haematol.2013.091025. (PMID: 24323983)
• 8 Liss BJ, Vehreschild JJ, Cornely OA. et al. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection 2012; 40 (06) 613-619
• 9 Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis 2005; 40 (Suppl. 04) S240-S245 DOI: 10.1086/427329. (PMID: 15768329)
• 10 Ullmann AJ, Akova M, Herbrecht R. et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 2012; 18 (Suppl. 07) 53-67
• 11 Cornely OA, Bassetti M, Calandra T. et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18 (Suppl. 07) 19-37 DOI: 10.1111/1469-0691.12039. (PMID: 23137135)
• 12 Chen SC, Perfect J, Colombo AL. et al. Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM. Lancet Infect Dis 2021; 21 (12) e375-e386 DOI: 10.1016/S1473-3099(21)00203-6. (PMID: 34419208)
• 13 Yang E, Choi EJ, Park HS. et al. Comparison of invasive fungal diseases between patients with acute myeloid leukemia receiving posaconazole prophylaxis and those not receiving prophylaxis: A single-center, observational, case-control study in South Korea. Medicine (Baltimore) 2021; 100 (20) e25448 DOI: 10.1097/MD.0000000000025448.
• 14 Medeiros BC. Management of invasive Aspergillosis in acute myelogenous leukemia. Clin Adv Hematol Oncol 2016; 14 (07) 502-504 (PMID: 27379944)
• 15 Donnelly JP, Chen SC, Kauffman CA. et al. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020; 71 (06) 1367-1376
• 16 Ullmann AJ, Akova M, Herbrecht R. et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 2012; 18 (Suppl. 07) 53-67
• 17 Cornely OA, Alastruey-Izquierdo A, Arenz D. et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019; 19 (12) e405-e421
• 18 Hoenigl M, Salmanton-García J, Walsh TJ. et al. Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology. Lancet Infect Dis 2021; 21 (08) e246-e257
• 19 Stahl M, Narendra V, Jee J. et al. Neutropenia in adult acute myeloid leukemia patients represents a powerful risk factor for COVID-19 related mortality. Leuk Lymphoma 2021; 62 (08) 1940-1948 DOI: 10.1080/10428194.2021.1885664. (PMID: 34180767)
• 20 Classen AY, Henze L, von Lilienfeld-Toal M. et al. Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO). Ann Hematol 2021; 100 (06) 1603-1620 DOI: 10.1007/s00277-021-04452-9. (PMID: 33846857)
• 21 Cornely OA, Maertens J, Winston DJ. et al. Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia. N Engl J Med 2007; 356 (04) 348-359 DOI: 10.1056/NEJMoa061094. (PMID: 17251531)
• 22 Mellinghoff SC, Panse J, Alakel N. et al. Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Ann Hematol 2018; 97 (02) 197-207
• 23 European Medicines Agency. Venclyxto : EPAR – Product Information. 2016 June 25, 2021 [cited 2022 October 3 ].. Accessed December 19, 2022 at: https://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-information_en.pdf
• 24 Stemler J, de Jonge N, Skoetz N. et al. Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association. Lancet Haematol. 2022; 9 (05) e361-e373
• 25 Stemler J, Koehler P, Maurer C. et al. Antifungal prophylaxis and novel drugs in acute myeloid leukemia: the midostaurin and posaconazole dilemma. Ann Hematol 2020; 99 (07) 1429-1440 DOI: 10.1007/s00277-020-04107-1. (PMID: 32514626)