Evaluation for the Need of Antifungal Prophylaxis In High Risk Hematologic Patients.
Authors: Pérez Olga , Aguilar Manuela , Martín Almudena , Falantes Jose , Montero Isabel , González Jose , Martino Maria Luz , Parody Rocio , Espigado Ildefonso 
Published: October 2019

Abstract
Abstract 4547

Background
Fungal infections remain a vital threat to the immunocompromised patient. Due to the high mortality rate of invasive mycoses, antifungal prophylaxis and prevention appear appropriate in some settings. Patients (pts) with prolonged and severe neutropenia or recipients of allogeneic hematopoietic stem cell transplantation (HSCT) appear to be at high risk for filamentous fungal infections, which are associated with low survival rates. However, there is no consensus on the optimal prophylaxis, eligible patients or its effectiveness and clinical impact.

Objective
To analyze the need for antifungal prophylaxis in Acute Leukemia patients receiving chemotherapy and the effectiveness of fluconazol, followed by posaconazol if GVHD developed, in recipients of allo-HSCT as antifungal prophylaxis.

Methods and patients
Period: from june’07 through june’09. Acute leukemia adult patients receiving chemotherapy as induction or re-induction therapy did not received primary antifungal prophylaxis. Recipientes of Allo-HSCT received 400 mg/d of fluconazole until discharge followed by 200 mg/8h of posaconazole if graft-versus-host disease (GVHD) developed, until its resolution. Patients received secondary antifungal prophylaxis according to their IFI. There were 77 pts who presented 218 episodes of post-chemotherapy neutropenia (80 in ALL and 138 in AML), 207 received no antifungal prophylaxis. On the other hand, we analyzed 40 consecutive Allo-HSCT adult recipients with an average age of 39 years (15-65) followed as in-patient and out-patient basis during a mean period of 18 months (3-24). Standard myeloablative or reduced intensity conditioning schemes were used and donors were HLA-identical sibling (27), unrelated donor (8) and umbilical cord blood (5). Diagnoses: AML (21), ALL (10), NHL (3), MDS (2), CML (2), HL (1) and AAS (1). The GVHD prophylaxis was according to standard protocols with MTX and CsP/MMF or standard umbilical cord blood protocols. Non-normal distribution data were expressed as median values (range). Chi-square test or Fisher exact test were used to compare differences between groups of categorical data. Differences were considered statistically significant for p-values < 0.05. All statistical analyses were performed using SPSS 16.0 software (Chicago, IL).

Results
Acute leukemia patients: There were 8 proved or probable fungal infections (EORTC/MSG consensus), with an incidence of 3.6%. The incidence of IFI in the whole induction AML group was 2.4%, (6.9% in the consolidation AML group, 25% in the re-induction AML group) and 5.2% in induction LLA and no case (0%) in the re-induction ALL group. As etiology, Aspergillus Fumigatus (1), Aspergillus spp (4), Candida tropicalis (1) and Candida spp (2). There were 3 deaths caused by IFI (37.5% of IFI); two of them in the re-induction AML group.
Allogenic hematopoietic stem cell transplantation recipients: 33 patients received fluconazole (82.5%) and 4 pts (10%) fluconazole followed by posaconazole. Other 3 received posaconazole (2) or voriconazole 200 mg/12 hours (1) as secondary prophylaxis since the conditioning. There were 7 cases of IFI (incidence of 17.5%), 3 proved IFIs and 4 probable IFIs. As etiology, Aspergillus Fumigatus (2), Aspergillus spp (4) and Candida albicans (1). Six patients had received fluconazole and one (candidiasis), fluconazole and posaconazole. The mortality attributable to IFI were 4 cases (57% of IFI). There was no IFI in the group of 9 pts without GVHD and all IFIs occurred in patients treated for GVHD.

Conclusions
1) Patients in re-induction of AML may require an effective prophylaxis against fungal infections, but not AML during induction or ALL in any situation. 2) The prophylaxis regimen studied in allogenic HSCT recipients was effective in preventing IFIs in patients without GVHD but not in patients with GVHD, particularly in the case of filamentous fungi. 3) The overall incidence of IFI in allo-HSCT was similar to that reported in other series of high risk and mortality from IFI similar to that described in recent years. 4) Patients with GVHD require more effective antifungal prophylaxis regimens and are candidates for clinical trials.

Disclosures:
No relevant conflicts of interest to declare.