Invasive fungal diseases caused by rare pathogens in patients after hematopoietic stem cell transplantation (HSCT) & chemotherapy

Abstract

Background: The number of publications on the invasive fungal diseases caused by rare pathogens (rare IFD) after HSCT and chemotherapy is limited. Method(s): From 2008 to 2017 in R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation (CIC725) have been performed 2738 HSCT including 1845 allogeneic (allo-HSCT) and 893 autologous HSCT (auto- HSCT). During the observation period 40 probable and proven rare IFD (EORTC/ MSG 2008 criteria) cases were diagnosed in children and adults with hematological malignances and non-malignant hematological diseases after allo-HSCT (n=30), auto-HSCT (n=2), and chemotherapy (n=8). The median follow up time for rare IFD cases was 3 months; for survivors - 30 months. Result(s): Incidence of rare IFD in HSCT recipients was 1,5%, it was higher after allo- HSCT (1,6%) than auto-HSCT (0,2%) (p<0,01). In 8 patients, this complication developed after CT and 4 of them proceed to allo-HSCT. The most frequent underlying diseases were ALL (33%) and acute AML (30%). The median time of onset of rare IFD after allo-HSCT - 104 (21-1057) days, auto-HSCT - 138 (60-216), after start of CT - 161 (79-189). Etiology of rare IFD was identified by culture in 65% cases: Rhizopus spp. - 27%, Paecilomyces spp. - 7%, Fuzarium spp. - 5%, Malassezia furfur - 5%, Trichosporon asahii - 3%, Scedosporiumapiosperium - 2%, Scopulariopsis gracilis - 2%, Rhizomucor pusillus - 2%, Lichtheimia corymbifera - 2%, mix rare IFD with Rhizopus spp.+ Paecilomyces spp. - 5%, Paecilomyces spp.+ Fuzarium spp. - 5%. 35% cases were diagnosed by microscopy. Antifungal therapy was used in all patients: lipid amphotericin B (L-AmB) - 30%, L-AmB+ caspofungin - 22,5%, voriconazole - 17,5%, posaconazole (posa) - 12,5%, L-AmB + posa - 10%, and echinocandins - 7,5%. Overall survival at 12 weeks from the diagnosis of rare IFD was 50%. The 12- weeks overall survival was better in patients after CT and auto-HSCT (80%) than allo- HSCT (42%), p=0,048. Conclusion(s): The incidence of rare IFD in HSCT recipients was 1,5%. Rare IFD is a late complication after chemotherapy and HSCT and usually develops after or in combination with invasive aspergillosis. Higher incidence and worst prognosis rare IFD is observed in allo-HSCT recipients.