CLINICAL, LABORATORY AND X-RAY PECULIARITIES OF INVASIVE ASPERGILLOSIS IN B-CELLULAR LYMPHOMS PATIENTS

The study included 108 patients with B-cell lymphoma which had complication with invasive aspergillosis, 57 patients with Hodgkin lymphoma (HL) and 51 patients with non-Hodgkin lymphoma (NHL). All patients in both groups received chemotherapy before the development of invasive aspergillosis, 73% of patients with HL and 67% patients with NHL received chemotherapy for induction and consolidation of remission. The main predictive factors for IA in patients with HL and NHL were: prolonged lymphocytopenia (70% vs 48%), agranulocytosis (64% vs 71%), use of glucocorticosteroids as part of treatment protocol (61% vs 85%), presence of B – symptoms (63% vs 48%), respectively. In most cases nosocomial invasive aspergillosis was diagnosed in both groups: 65% vs 83% respectively. We identified etiological agents in Hodgkin and non-Hodgkin lymphoma patients: A. fumigatus (50% vs 39%), A. niger (43% vs 33%) and A. flavus (7% vs 8%). The lungs were involved in 100% cases, in group with NHL patients 6% had combined lesions in lungs and other organs and different types of tissues. Clinical manifestation of IA was nonspecific in both groups: fever – 83% vs 76%, cough – 75% vs 59%, respiratory insufficiency – 50% vs 40%, respectively. CT-signs of IA were also nonspecific in both groups: infiltrative (75% vs 66%), focal changes (61% vs 63%), and «ground-glass opacity» (28% vs 31%), respectively. In most cases patients were treated with voriconazole in both patients (88% vs 98%). Overall 12-weeks survival in patients with Hodgkin lymphoma and invasive aspergillosis was 84%, in patients with non-Hodgkin lymphoma and invasive aspergillosis – 81%.

1. Engholm G, Ferlay J, Christensen N, Bray F, Gjerstorff ML, Klint A et al. NORDCAN: Cancer Incidence, Mortality, Prevalence and Survival in the Nordic Countries, Version 7.3 (08.07.2016). Association of the Nordic Cancer Registries. Danish Cancer Society. Available from http://www.ancr.nu, accessed on 28/10/2016.

2. Kaprin А, Starinskiy V, Petrova G. Malignancies in Russia in 2015 (incidence and mortality) [Злокачественные новообразования в России в 2015 году (заболеваемость и смертность)], Herzen Research Institute of Oncology, Moscow, 2017.

3. Cancer Research UK, http://www.cancerresearchuk. org/health-professional/cancer- statistics/,Accessed November 2016.

4. Поддубная И.В. Клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Москва, 2014.

5. Волкова А.Г., Попова М.О., Екушев К.Е., Зиннатуллин И.Р., Николаев Ю.И., Богомолова Т.С. и др. Роль бронхоскопии в диагностике инвазивного аспергиллеза легких у детей после трансплантации гемопоэтических стволовых кроветворных клеток. Российский журнал детской гематологии и онкологии, 2015, 2: 72-76.

6. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clinical Infectious Diseases, 2008, 46(3): 327-60.

7. Krcmery V. Antifungal chemotherapeutics. Medical Principles and Practice, 2005, 14(3): 125-13.

8. Kousha M, Tadi R, Soubani A. Pulmonary aspergillosis: a clinical review. European Respiratory Review, 2011, 20(121): 156-172.

9. Попова М.О., Зубаровская Л.С., Климко Н.Н., Вавилов В.Н., Волкова А.Г., Зюзгин И.С. Инвазивные микозы при трансплантации гемопоэтических стволовых клеток. Терапевтический архив, 2012, 7: 50-57.

10. Klimko N, Kozlova Y, Khostelidi S, Shadrivova O, Borzova Y, Burygina E et al. The burden of serious fungal diseases in Russia. Mycoses, 2015, 58(5): 58-62.

11. Klimko NN, Shadrivova OV, Khostelidi SN. Invasive aspergillosis in Saint Petersburg, Russia: analysis of 445 proven and probable cases. Mycoses: Diagnosis, Therapy and Prophylax is of Fungal Diseases, 2013, 56(3): 113.

12. 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. Haematologyca, 2006, 91: 1068-72.

13. De Pauw B, Walsh TJ, Donnelly JP. 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. Clinical Infectious Diseases, 2008, 46(12): 1813-21.

14. Gil L, Kozlowska-Skrzypczak M, Mol A, Poplawski D, Styczynski J, Komarnicki M. Increased risk for invasive aspergillosis in patients with lymphoproliferative diseases after autologous hematopoietic SCT. Bone Marrow Transplant, 2009, 43(2): 121-6.

15. Lortholary O, Gangneux JP, Sitbon K et al. French Mycosis Study Group. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005–2007). Clinical Microbiology and Infection, 2011, 17(12): 1882- 1889.

16. Шадривова О.В., Фролова Е.В., Филиппова Л.В., Учеваткина А.Е, Хостелиди С.Н., Чернопятова Р.М. и др. Клинико-иммунологические особенности инвазивного аспергиллеза у больных с лимфомой Ходжкина. Клиническая онкогематология, 2014, 2: 233-238.

17. Georgiadou S, Sipsas N, Marom E, Kontoyiannis DP et al. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clinical Infectious Diseases, 2011, 52: 1144-55.

18. Масчан А.А., Клясова Г.А., Веселов А.В. Обзор рекомендаций американского общества по инфекционным болезням по лечению аспергиллеза. Методические рекомендации, 2008: 133-170.

19. Nivoix Y, Velden M, Letscher-Bru V, Moghaddam A, Natarajan-Amé S, Fohrer C et al. Factors associated with overall and attributable mortality in invasive aspergillosis. Clinical Infectious Diseases, 2008, 47: 1176-84.