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Facchin, G.1; Candoni, A.1; Busca, A.2; Lazzarotto, D.1; Cattaneo, C.3; Nadali, G.4; Klimko, N.5; Del Principe, M. I.6; Castagnola, C.7; Verga, L.8; Calore, E.9; Capelli, D.10; Perruccio, K.11; Melillo, L.12; Pagano, L.13

doi: 10.1097/
Poster Session II: Infectious diseases

1Clinica ematologica, ASUI-University of Udine, Udine

2S.C. Ematologia, AO Città della Salute e della Scienza, Torino

3S.C. Ematologia, Spedali Civili, Brescia

4U.O.C. Ematologia, AOUI, Policlinico GB Rossi, Verona, Italy

5Metchnikov North-Western State Medical University, St. Petersburg, Russian Federation

6Ematologia, Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Roma

7Dipartimento Oncoematologico, Fondazione ICRRS Policlinico San Matteo, Pavia

8Clinica Ematologica, Ospedale S Geraldo, Monza

9Clinica di Oncoematologia pediatrica, Dipartimento di Salute della Donna e del Bambino, Azienda Ospedaliero-Universitaria, Padova

10Clinica Ematologica, Ospedali Riuniti di Ancona, Ancona

11Oncoematologia Pediatrica, Ospedale SM Misericordia, Perugia

12Divisione di Ematologia, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo

13Istituto di Ematologia, Polo Onco-Ematologico Fondazione Policlinico A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

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Invasive Fungal Infections of the Central Nervous System (IFI-CNS) are very rare and life threatening complications and no specific epidemiologic data are available in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) recipients.

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We describe the incidence, clinical characteristics and outcome of IFI-CNS detected, over a 7 years period, in 13 Allo-HSCT Centers.

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Between January 2010 and December 2016, 3866 Allo-HSCT were performed in 13 HSCT Centers; in this cohort of patients there were 24 consecutive diagnosis of IFI-CNS with an incidence of 0,62%. The diagnosis was made by biopsy ± histological examination, serum or/and liquor biomarkers and radiological examination (CT ± MRI). All cases of IFI-CNS were proven (58%) or probable (42%) according to the EORTC criteria.

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The median age of patients was 39 years (range 12-63) and acute leukaemia (10 myeloid and 7 lymphoid) was the most common underlying haematologic disease (71%); 54% of patients (13/24) had severe neutropenia (granulocytes less than 500/mmc) at the onset of infection and there was a concomitant extra CNS involvement (mainly lung) in 75% of cases. Among the 24 patients with IFI-CNS, 16 had received an Allo-HSCT from unrelated donors, 4 from a HLA-id family donor and 4 from a haploidentical donor. Of 14 proven cases 12 were caused by moulds (7 aspergillosis, 3 mucormycosis, 1 fusariosis, and 1 scedosporidiosis) and 2 by yeasts (1 cryptococcosis and 1 trichosporonosis). All the 10 probable infections were caused by Aspergillus spp. The fungal biomarkers (galattomannan and others) on cerebrospinal fluid were performed in 11/24 (46%) of cases and were positive in 73% (8/11). The brain diagnostic biopsy was performed in 8% of cases and a biopsy from other concomitant involved sites was performed in 21% of cases. All patients received antifungal therapy mainly with amphotericine (14/24-58%) or voriconazole (11/24-46%). A combination antifungal therapy was administered in 33% (8/24) of cases. The antifungal therapy was coupled with neurosurgical intervention only in 17% of cases. The overall response rate (ORR) to treatment was 38%. Median follow-up of 24 patients with IFI-CNS was 7 months (range 0,3-63) with a 12 months overall survival (OS) probability of 23% (Figure 1). The overall mortality was 75% (18/24) and the IFI-SNC attributable mortality was 44% (8/18).



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a)Proven or Probable IFI-CNS remains a very rare infectious complication after Allo-HSCT with an incidence of 0,62% in this recent epidemiological survey. The most important causative agent remains Aspergillus sp and a concomitant extra CNS involvement (mainly lung) is very common (in 75% of the reported cases).

b)The fungal biomarkers on cerebrospinal fluid, when performed, were highly informative (positive in 73% of our case series). This underlines that diagnostic lumbar puncture should be encouraged when we suspect an IFI-CNS to confirm the diagnosis and to promptly start a targeted therapy.

c)The CNS biopsy and the surgical approach were performed in a minority of cases.

d)Despite the availability of a broad spectrum of antifungal drugs the ORR remains poor (38% in the present series) and the probability of OS at 12 months was only 23%. New drugs with better permeability in the CNS and less interactions with immunosuppressive agents (such as isavuconazole) and/or more aggressive diagnostic and therapeutic approach (combination antifungal therapy coupled with surgery) could improve the outcome of IFI-CNS in Allo-HSCT recipients.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.