PS1285 INVASIVE FUNGAL DISEASES IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION RECIPIENTS WITH HODGKIN'S LYMPHOMA
Authors: Popova M. , Rogacheva Y. , Volkova A. , Markova I. , Frolova A. , Shvetcov A. , Nikolaev I. , Goloshchapov O. , Ignatieva S. , Bogomolova T. , Kozlov A. , Lepik K. , Yuriy Z. , Stelmakh L. , Kondakova E. , Gevorgian A. , Beynarovich A. , Borzenkova E. , Darskaya E. , Vladovskaya M. , Bondarenko S. , Moiseev I. , Baykov V. , Mikhailova N. , Zubarovskaya L. , Klimko N. , Afanasyev B. 
Published: June 2019

Background:

Data on invasive fungal disease (IFD) in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients with relapsed/refractory Hodgkin's lymphoma (r/r HL) are limited. Outcome of allo‐HSCT in patients with prior IFD is still a subject of controversy.

Aims:

The aim is to study the epidemiology of IFD in allo‐HSCT recipients with r/r HL.

Methods:

Single center prospective observational study included 86 patients with classical r/r HL who underwent allo‐HSCT from 2002 to 2018. The median age was 27 (13–49) y.o., children (<18 yo) – 13% (n = 11). Allo‐HSCT from MUD was performed in 45,4% (n = 39), MRD – 24,4% (n = 21), MMUD – 15,1% (n = 13), haplo – 15,1% (n = 13), with RIC (100%) and predominantly PTCY‐based GvHD prophylaxis (71%). Primary antifungal prophylaxis was fluconazole in 85%, secondary – voriconazole (100%). EORTC/MSG 2008 criteria for diagnosis and response to therapy were used. In pts with CT‐scan lung lesions before allo‐HSCT bronchoscopy with BAL was used. “Active IFD” means IFD diagnosed just before HSCT. Median follow‐up time was 12 months [1–71].

Results:

Incidence of pre‐existing IFD in allo‐HSCT recipients with r/r HL was 12,8% (n = 11). All cases of IFD prior to HSCT were invasive aspergillosis (IA) with lungs involvement. Antifungal therapy before allo‐HSCT was used in 81,8% pts with median duration – 2 months. Complete response to antifungal therapy was in 45,4% pts, partial response or stabilization – 36,4%, and 18,2% pts had an “active IFD”. After allo‐HSCT all pts received voriconazole as an antifungal therapy or secondary prophylaxis. Cumulative incidence of relapse or progression of IA after allo‐HSCT was 18,2% with the median 49 day [19–79] of onset after HSCT, which were successfully treated with voriconazole. Incidence of IFD after allo‐HSCT for naïve patients was 17,6% (n = 13/74). Etiology of IFD after allo‐HSCT was IA – 69%, invasive candidiasis (IC) – 15%, mucormycosis – 8%, and combined IFD caused by Aspergillus fumigatus + Rhizopus stolonifer ‐ 8%. The median day of onset of IFD after allo‐HSCT was day+ 114 [1–489]. The main site of infection were lungs (88%), the main clinical symptom – febrile fever (100%). Antifungal therapy was following: voriconazole – 59%, micafungin – 17%, posaconazole – 8%, lipid amphotericin B – 8% and combination lipid amphotericin B with caspofungin – 8%. Overall survival (OS) at 12 weeks from the IFD diagnosis after allo‐HSCT was 80%. The 2‐year OS in children and adult with r/r HL after allo‐HSCT was 73,3%. Development of IFD after allo‐HSCT do not decrease the 2‐year OS rate (69,2% vs 74%, p = 0,77). The impact of prior IFD on 2‐year OS in allo‐HSCT recipients was not statistically significant in all group (63,6% vs 74,7%, p = 0,47), and separately in children and adults.

Summary/Conclusion:

Incidence of pre‐existing IFD in children and adults with r/r Hodgkin's lymphoma allo‐HSCT recipients was 12,8%. Incidence of IFD after allo‐HSCT in naïve patients with Hodgkin's lymphoma was 17,6%. The major etiology agent as before as after allo‐HSCT were Aspergillus spp. IFD was a late complication after allo‐HSCT. Despite the high incidence of IFD before or after allo‐HSCT didn’t influence the outcome in children and adults with r/r Hodgkin lymphoma.