A Closer Look at GVHD Prophylaxis and Fungal Infections

Haploidentical hematopoietic stem cell transplantation involves stem cell transplants from donors whose human leukocyte antigens (HLA) are a partial match to the recipients’. The use of haploidentical transplants expanded the pool of possible stem cell donors but brought with it an increased risk of graft-versus-host-disease (GVHD). To deal with that problem, transplant centers looked for other ways to prevent GVHD besides the standard approach of cyclosporine A (CsA) paired with a short course of methotrexate (scMTX). Post-transplant cyclophosphamide (PTCy) is an alternative that has gained traction. But by eliminating donor T cells, PTCy opens the door to possible infections, and studies have shown an increased risk of pre-engraftment bacteremia and reactivation of cytomegalovirus. Fungal disease also seems to be a challenge with haploidentical transplants that use PTCy for GVHD prophylaxis, but uncertainty remains and many details are unknown.

Researchers at Taipei Veterans General Hospital in Taiwan attempted to fill in some of the blanks with a retrospective study of adult patients who underwent hematopoietic stem cell transplants at the hospital’s blood and marrow transplant center from 2003 to 2023. They identified 580 patients. The hematological diseases necessitating stem cell transplants included acute myeloid leukemia (40% of the patients), acute lymphoblastic leukemia (20%) and non-Hodgkin lymphoma (10%). The vast majority — 500 — of the patients had conventional donors, including matched siblings and people who were HLA-matched but unrelated to the stem cell recipient. For them, CsA plus scMTX was used as a way to reduce the risk of GVHD. The other 80 patients had haploidentical donors with PTCy as GVHD prophylaxis. All the patients also received treatment to prevent antifungal infections that included either echinocandins (micafungin, anidulafungin or caspofungin) or azoles (fluconazole or voriconazole).

The results reported by corresponding author Yao-Chung Liu and colleagues In the April 2025 issue of the Journal of Microbiology, Immunology and Infection — and published earlier online — showed that 90 patients (15.5%) in the overall group developed fungal disease. There was little difference between the two types of GVHD prophylaxis: 78 of the 500 (15.6%) of patients treated with CsA plus scMTX experienced fungal disease compared with 12 of the 80 (15%) treated with PTCy. The authors noted that previous research had shown a range of fungal disease among haploidentical patients from 10% to 18%so this result is consistent with other studies.

Just over half of the patients in the PTCy group received echinocandins to prevent fungal infections, while just over 80% of the CsA plus scMTX group received fluconazole. “The change in fungal prophylaxis might have provided potential activity against Candida spp. and Aspergillus spp. leading to similar IFD [invasive fungal disease] rates observed in different GVHD prophylaxis,” wrote Liu and colleagues.

Liu and his colleagues noted that fungal disease led to lower survival rates. In the overall group, those with fungal disease had an overall survival of 8.3 months, a disease-free survival of 5.63 months and GVHD-free relapse-free survival (GRFS) of 3.1 months. They noted that among those without fungal disease, the haploidentical patients-PTCy patients were noninferior to the conventionally matched patients treated with CsA plus scMTX as far as overall and disease-free survival and had an advantage when it came to GRFS.

They noted, though, that the cytomegalovirus reaction rate was higher in the haploidentical group-PTCy group than in the conventional match-CsA plus scMTX group (77.5% vs. vs.53.4%). They noted that the cytomegalovirus reactivation didn’t seem to affect fungal disease. They advised that anti-cytomegalovirus prophylactic antivirals might be warranted in patientsreceivingd PTCy GVHD prophylaxis.

The results from this study showed that the haploidentical patients had much lower rates of acute GVHD than those who received more conventional transplants. In the overall group, 203 (35%) patients experienced acute GVHD and approximately half of the cases were more severe cases of GVHD (grade 3 and 4). But in the haploidentical group, only 18.8% (15 of 80) of the patients experienced acute GVHD compared with 37.6% (188 of 500) of the patients with the more conventionally matched donors.