Invasive Fungal Infection in Haematopoietic Stem Cell Transplant Recipients: Epidemiology from the Transplant Physician’s Viewpoint

Abstract

The practice of hematopoietic stem cell transplantation (HSCT) has undergone many changes that affect the likelihood that a given patient would develop an invasive fungal infection (IFI). The risks for IFI and the types of IFI that may occur are not continuous over the time course after transplantation. IFIs vary with the events that occur during the pre-engraftment neutropenic period, the early post-engraftment period until approximately day 100 post-transplant, and those in the late post-engraftment period after day 100. A number of well-recognized transplant recipient-, transplant procedure-, and transplant complication-related factors play a role in the likelihood of IFI. Important recipient-related factors include age, state of the underlying disease for which the HSCT is being done, and treatment-related history. Transplant procedure-related factors include the type of transplant (autologous or allogeneic), the use of and timing of anti-fungal prevention strategies including whether or not the transplant was conducted in a protected environment to minimize environmental exposure to mould conidia, the choice of conditioning (myeloablative or non-myeloablative), human leucocyte antigen-relatedness [autologous, matched related, mismatched related (including haploidentical pairings), unrelated (matched or mismatched)], stem cell source (bone marrow, peripheral, or cord blood), stem cell dosing, and stem cell product processing (red cell, plasma, or T-lymphocyte depletions, or CD34 selections). Transplant-related complications include duration of pre-engraftment period of neutropenia, graft failure or rejection, the degree of cytotoxic conditioning therapy-related intestinal mucosal damage, acute and chronic graft-versus-host disease (GvHD), the use of corticosteroids for the prevention or management of GvHD, the presence of cytomegalovirus infection and disease. The interaction of these factors over a given patient's journey through HSCT conspires to promote or reduce the overall IFI risk and set the conditions for the development of any given IFI. The following discussion attempts to look at this from the perspective of the transplant physician struggling to account for these interactions and their attendant risks for IFI.

Antifungal prophylaxis in hematopoietic stem cell transplant recipients: the unfinished tale of imperfect success

“…Yet, the risk for IFI and spectrum of possible pathogen exposure is heterogeneous over the time course of the transplant. 10,11 Because change in the profile of contemporary transplant recipients (for example, fewer patients with CML, transplantation in older patients with comorbidities) and transplantation procedures (for example, more nonmyeloablative HSCTs, peripheral and cord blood SCTs, increasing stem cell doses, CD34 stem cell selection/T-cell depletion) have evolved constantly, 10 antifungal prophylaxis has been a 'moving target' where consensus is difficult. Some examples are worth mentioning.…”

Population Pharmacokinetics of Liposomal Amphotericin B and Caspofungin in Allogeneic Hematopoietic Stem Cell Recipients

“…Infection rates range between 10 and 25%, and overall mortality is 35 to 50% for invasive candidiasis and 65 to 90% for invasive aspergillosis and infections by other filamentous fungi (5,14).…”

Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

“…Depending on the presence of well-characterized risk factors, rates of infection by opportunistic fungal pathogens are between 10 and 25%. The case fatality rates vary between 35 and 50% for invasive candidiasis and 65 and 90% for invasive aspergillosis and infections by other filamentous fungi (8,15).…”