THE EFFICACY OF POSACONAZOLE FOR PROPHYLAXIS OF INVASIVE MYCOSES IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

Efficacy of posaconazole for prophylaxis was evaluated in 77 chemotherapy cycles in 59 patients with acute myeloid leukemia (AML) aged 39 (17–62) years from 2012  till 2017. Posaconazole was given in oral suspension 200 mg three times a day after meal during chemotherapy cycle or on 1st  day after the cycle. Administration of posaconazole predominated in patients with de novo AML (84.5%) on 1st induction cycles (66.3%). Neutropenia was present in all patients with median duration of 22 days. Median duration of prophylaxis was 21  (2–57)  days. Posaconazole prophylaxis was interrupted in 28  (36.4%) of 77 cases, mainly due to diarrhea (28.6%). In 17 (61%) of 28 cases prophylaxis was resumed within a median of 3 days. In 72 (93.5%) of cases duration of posaconazole prophylaxis was ≥ 7 days, in 5 (6.5%) cases < 7 days. Efficacy of prophylaxis was evaluated in cases of posaconazole duration ≥ 7 days. Invasive pulmonary aspergillosis (probable) was in 2 (2.7%) of 72 cases. Administration of posaconazole with duration ≥ 7 days was in 46 cases on chemotherapy cycle, in 26 cases – on first day after the cycle. Patients using Posaconazole after a course of chemotherapy in comparison with patients receiving the drug in the first days of the course had significantly less interruptions of prophylaxis (11,5% vs 41,3%, p=0.009) and a reduction in duration of Posaconazole using (19 days vs 27 days, p=0.007).One case of invasive aspergillosis was registered in each group.

We confirmed the  efficacy of posaconazole  for prophylaxis of invasive mycoses  in patients  with AML. Administration of posaconazole prophylaxis on first day after the end of chemotherapy cycle results in saving of drug by reducing duration of posaconazole using by 8 days and does not increase the incidence of invasive mycoses.

1. Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica, 2006, 91(8): 1068-75.

2. Клясова Г.А., Охмат В.А., Васильева В.А., Попова М.О., Капорская Т.С., Свешникова Ю.В. и др. Инвазивные микозы у больных острыми лейкозами и у реципиентов гемопоэтических стволовых клеток. Результаты многоцентрового проспективного наблюдательного исследования в России (RIFI). Гематология и трансфузиология, 2016, 61(1, Suppl. 1): 19.

3. Nucci M, Garnica M, Gloria AB, Lehugeur DS, Dias VC, Palma LC, et al. Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil. Clin. Microbiol. Infect., 2013, 19(8): 745-51.

4. Pagano L, Caira M, Nosari A, Rossi G, Viale P, Aversa F, 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): 1502-3.

5. Michallet M, Bénet T, Sobh M, Kraghel S, El Hamri M, Cannas G, et al. Invasive aspergillosis: an important risk factor on the short-and longterm survival of acute myeloid leukemia (AML) patients. Eur. J. Clin. Microbiol. Infect. Dis., 2012, 31(6): 991-7.

6. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med., 2007, 356(4): 348-59.

7. Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frere P et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3-2009 update. Bone Marrow Transplant., 2011, 46(5): 709-18.

8. Клясова Г.А. Антимикробная терапия. В кн.: Программное лечение заболеваний системы крови: сборник алгоритмов диагностики и протоколов лечения заболеваний системы крови. Под ред. В.Г. Савченко. М.: Практика, 2012: 827–54.

9. De Pauw B, Walsh TJ, Donnelly JP, Stevens, DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/ MSG) consensus group. Clin. Infect. Dis., 2008; 46(12): 1813-21.

10. Ananda-Rajah MR, Grigg A, Downey MT, Bajel A, Spelman T, Cheng A, et al. Comparative clinical effectiveness of prophylactic voriconazole/ posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period. Haematologica, 2012, 97(3): 459-63.

11. Vehreschild JJ, Rüping M, Wisplinghoff H, Farowski F, Steinbach A, Sims R, et al. Clinical effectiveness of posaconazole prophylaxis in patients with acute myelogenous leukaemia (AML): a 6 year experience of the Cologne AML cohort. J. Antimicrob. Chemother., 2010, 65(7): 1466-71.

12. Pagano L, Caira M, Candoni A, Aversa F, Castagnola C, Caramatti C, et al. Evaluation of the practice of antifungal prophylaxis use in patients with newly diagnosed acute myeloid leukemia: results from the SEIFEM 2010-B registry. Clin. Infect. Dis., 2012, 55(11): 1515-21.

13. Girmenia C, Frustaci AM, Gentile G, Minotti C, Cartoni C, Capria S, et al. Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience. Haematologica, 2012, 97(4): 560-7.

14. Duarte RF, Sánchez-Ortega I, Cuesta I, Arnan M, Patiño B, Fernández de Sevilla A, et al. Serum galactomannan–based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis. Clin. Infect. Dis., 2014, 59(12): 1696-702.

15. Maertens J. Primary antifungal prophylaxis. Available at: https://www.ebmt.org/ContentsResources/Library/ECIL/Documents/2014%20ECIL5/ECIL5antifungalprophylaxis%20%2020062014%20Final.pdf Accessed October 2017.