How I perform hematopoietic stem cell transplantation on patients with a history of invasive fungal disease

Abstract

Hematopoietic transplantation is the preferred treatment for many patients with hematologic malignancies. Some patients may develop invasive fungal diseases (IFDs) during initial chemotherapy, which need to be considered when assessing patients for transplantation and treatment posttransplantation. Given the associated high risk of relapse and mortality in the post-hematopoietic stem cell transplantation (HSCT) period, IFDs, especially invasive mold diseases, were historically considered a contraindication for HSCT. Over the last 3 decades, advances in antifungal drugs and early diagnosis have improved IFD outcomes, and HSCT in patients with a recent IFD has become increasingly common. However, an organized approach for performing transplantation in patients with a prior IFD is scarce, and decisions are highly individualized. Patient-, malignancy-, transplantation procedure-, antifungal treatment-, and fungus-specific issues affect the risk of IFD relapse. Effective surveillance to detect IFD relapse post-HSCT and careful drug selection for antifungal prophylaxis are of paramount importance. Antifungal drugs have their own toxicities and interact with immunosuppressive drugs such as calcineurin inhibitors. Immune adjunct cytokine or cellular therapy and surgery can be considered in selected cases. In this review, we critically evaluate these factors and provide guidance for the complex decision making involved in the peri-HSCT management of these patients.

Graphical abstract

Figure 1.

Recommendations for peritransplantation management of high-risk patients for IFD relapse. ^aThe duration of secondary antifungal prophylaxis is individualized; consider stopping after up to 1 year post-HSCT (carefully evaluating for acute and chronic toxicities from antifungals) if patient is in CR, has polymorphonuclear leukocyte (PMN) count >1000 cells per mm³, and no signs or symptoms of active IFD. ^bResume mold-active prophylaxis if GVHD develops (acute or chronic) requiring systemic immunosuppressive therapy. ^cAny triazole antifungal administered with conditioning regimen (eg, busulphan, cyclophosphamide) or calcineurin inhibitors. ^dRole of surveillance with fungal biomarkers in asymptomatic patients receiving mold-active prophylaxis is unproven. MDR, multidrug resistant; TDM, therapeutic drug monitoring.

Figure 2.

Recommendations for peritransplantation management of low-risk patients for IFD relapse. ^aThe duration of secondary antifungal prophylaxis is individualized; consider stopping after up to 6 months post-HSCT (carefully evaluating for acute and chronic toxicities from antifungals) if patient is in CR, has polymorphonuclear leukocyte (PMN) count >1000 cells per mm³, and no signs or symptoms of active IFD. ^bResume mold-active prophylaxis if GVHD develops (acute or chronic) requiring systemic immunosuppressive therapy. ^cTriazole antifungal should be administered with conditioning regimen (eg, busulphan, cyclophosphamide) or calcineurin inhibitors and sirolimus. ^dRole of surveillance with fungal biomarkers in asymptomatic patients receiving mold-active prophylaxis is unproven. AMB, amphotericin B; TDM, therapeutic drug monitoring.