Voriconazole as secondary antifungal prophylaxis in stem cell transplant recipients (reply)

I do agree with Cordonnier and colleagues who in this issue of the Journal underline the importance of a proper definition of secondary antifungal prophylaxis (SAP) in patients with a previous invasive fungal disease (IFD). 1 The term secondary prophylaxis is only applicable to a population with inactive or apparently resolved disease.

With this premise, their recently published prospective, non-comparative study of SAP with voriconazole in allogeneic hematopoietic stem cell transplant (HSCT) recipients demonstrated that the triazole is an effective option in SAP of IFDs after HSCT. 2 This was strongly evident in patients with an aspergillus infection, considering that none of the 31 patients with a previous proven or probable invasive aspergillosis experienced recurrence of the disease after transplant. For the first time, a prospective study confirmed retrospective evidence showing that the probability of posttransplantation invasive aspergillosis and overall survival among patients who had resolution of radiographic abnormalities and receive SAP was no different from that of patients without prior invasive aspergillosis under primary antifungal prophylaxis. 1, 3

In my editorial on prophylaxis of IFDs in patients with hematologic disorders, I underlined the fact that the efficacy of SAP in patients with active infection or with persistent radiological abnormalities remains unclear. 4 As suggested by Cordonnier and colleagues, strictly speaking, the treatment with antifungal drugs of a controlled but not resolved IFD should not be defined as SAP. In these cases, other terms such as suppressive or continuous antifungal therapy may be more appropriate. On the other hand, an evidence-based antifungal approach in patients with an IFD not in complete remission who require urgent antileukemic treatment remains even more challenging. In real life, a large number of patients with hematologic malignancies undergo allogeneic HSCT despite unresolved IFD. When the underlying malignancy is at high risk of relapse or progression, an early transplant procedure may be required without time for a prolonged antifungal therapy and complete remission of the infection before transplant. This is being seen with increasing frequency in clinical practice and is a challenging issue. In retrospective studies of patients with prior IFD undergoing allogeneic HSCT, the infection was in partial remission, stable phase or progression in about half of the cases and persistent radiographic abnormalities were associated with increased risks of posttrans-plantation IFD. 3, 5 Preliminary data of an ongoing prospective, multicenter epidemiological survey of IFDs in allogeneic HSCT recipients among transplant centers of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) report 84 patients with an IFD diagnosed within the 12 months before transplant. In about 40% of these cases, the infection was in partial remission or active at the time of transplant, and the probability of relapse or progression of the infection and of IFD-related death was significantly higher compared to patients with prior IFD in complete clinical response at the time of transplant (C Girmenia and A Locasciulli on behalf of the GITMO, unpublished data, 2010).

Prior IFD is no longer a contraindication of allogeneic HSCT. However, while SAP in patients with a resolved infection is able to minimize the risk of relapse after transplant, patients with an active/not resolved IFD at the time of transplant continue to be at risk of a potentially fatal reactivation. The role of suppressive/continuous antifungal treatment and of preventive surgical resection of residual pulmonary lesions should be properly investigated in order to identify a tailored antifungal prevention strategy.