Foscarnet treatment of cytomegalovirus infection in haploidentical or unrelated donor transplants

Elisabetta Metafuni,Alida Dominietto,Emanuele Angelucci,Maria Teresa Van Lint,Andrea Bacigalupo,Simona Sica,Patrizia Chiusolo,Stefania Bregante,Luca Laurenti

doi:10.1038/s41409-018-0200-y

Abstract

We studied 97 patients who developed cytomegalovirus (CMV) viremia following an allogeneic hemopoietic stem cell transplant (HSCT) between 2010 and 2015, treated with foscarnet, with the aim of assessing efficacy and safety. The donor was unrelated in 30 patients (UD) and a family HLA-haploidentical donor (HAPLO) in 67 patients: the former (UD) received a prophylaxis for graft-versus-host disease (GvHD), based on antithymocyte globulin (ATG); the latter (HAPLO) received GvHD prophylaxis, based on post-transplant cyclophosphamide (PT-CY). Renal and hematological toxicity were defined according to NCI-CTCAE4 criteria. In univariate analysis, CMV response was 84% in HAPLO vs 59% in UD grafts (p = 0.01) and 90 vs 66% (p = 0.02) for patients with a CMV viral load within or over the median value. In multivariate analysis, the CMV viral load was the strongest predictor of response to foscarnet (p = 0.02), followed by donor type (p = 0.06). Renal impairment developed in 14% of the patients. Overall survival was 69%:, advanced phase at transplant (p = 0.01) and ATG-based regimens (p = 0.02), were the only two predicting factor. In conclusion, CMV response to foscarnet treatment is predicted by a lower CMV load and GvHD prophylaxis. Renal toxicity of foscarnet is not a limiting factor.

Highlights

Cytomegalovirus (CMV) infection is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT), and occurs in up to 80% of CMV-seropositive patients [1]
Neutrophil engraftment (>0.5 × 109/L) was achieved after a median interval of 17 and 18 days after hemopoietic stem cell transplant (HSCT) in the unrelated in patients (UD) and haploidentical donor (HAPLO) groups (Table 2); acute graft-versus-host disease (GvHD) grade II–IV developed in comparable proportion of patients in the two groups (Table 2)
We have shown in the present study that pre-emptive treatment of CMV infection with foscarnet yields higher response rates in patients grafted from HAPLO donors with post-transplant cyclophosphamide (PT-CY) as GvHD prophylaxis, as compared to patient grafted from UD donors receiving an antithymocyte globulin (ATG)-based regimen

Summary

Introduction

Cytomegalovirus (CMV) infection is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT), and occurs in up to 80% of CMV-seropositive patients [1]. A randomized study in 110 patients with CMV infection compared foscarnet with ganciclovir, the primary end point being survival without CMV disease or death. At 180 days [12], the event-free survival was 66 vs 73% for patients treated with foscarnet or ganciclovir (p = 0.6). Another randomized study reported a faster clearance of CMV antigenemia in the foscarnet group, as compared to ganciclovir group, with an overall transplant-related mortality (TRM) of 18%, with no difference in response or mortality in the two groups [13]

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