There is still no clear information about the incidence and consequences of infections
with cyclophosphamide (PTCy) administration as prophylaxis against graft-versus-host
disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Revealing the incidence of pre-vaccination bacterial and viral infections (cytomegalovirus
[CMV], herpes virus, and BK-polyomavirus hemorrhagic-cystitis), infection-related
mortality, and predictive factors associated with PTCy application after allo-HSCT
was the study aim.
Patients who underwent allo-HSCT from 9/10–10/10 HLA tissue-matched, unrelated donors
and received cyclophosphamide for post-transplant GVHD prophylaxis from 3 centers
between 2015 and 2020 were retrospectively reviewed. Infections that developed in
the first 100 days after transplantation were recorded.
Forty-one patients, M/F: 25/16, were included in the study. The mean age was 40.8
years (21–67), with 23 AML, 11 ALL, 3 NHL, 2 MDS, one biphenotypic leukemia, and 1
HL diagnosis. HLA tissue compatibility was 9/10 in 32 patients and 10/10 in 9 patients.
All patients received one myeloablative priming regimen [TBI (800–1200 cGy)+Flu (30
mg/m2×5), Cy (60 mg/kg×2) + TBI (1200 cGy), treosulfan (10 g/m2×3) + Flu (40 mg/m2×4)]. In GVHD prophylaxis, PTCy was administered 72 and 96 hours following transplantation
in combination with calcineurin inhibitors ± methotrexate ± mycophenolate mofetil.
Levofloxacin, valacyclovir, fluconazole, and trimethoprim-sulfamethoxazole were empirically
given to all patients along with the transplant preparation regimen.
At least one episode of febrile neutropenia (FEN) developed in all patients during
the transplantation process. More than one episode of FEN developed in 22% of the
patients. One patient died due to septic shock on post-transplant day 9. The incidence
of CMV infection requiring treatment was 36.6% in the first 100 days and 41.5% at
1 year. All patients except 1 were CMV IgG-positive before transplantation. CMV reactivation
was observed in 50% (15/15) of donor/patient CMV IgG (+/+). CMV reactivation was found
in 30% (3/7) of the donor/patient CMVIgG (–/+) patients. Only one of these patients
received antiviral therapy due to multiple reactivations. In 4 patients, CMV pneumonia
developed, and 3 of them died. The rate of polyomavirus-associated cystitis was 7.3%
(3/41). In the first year after transplantation, invasive fungal infection occurred
in only 4 patients (9.8%), herpes virus infection occurred in 1 patient. Three patients
received tenofovir–entecavir treatment because of anti-HBcIg positivity, and HBV reactivation
was not detected in any of the patients.
GVHD prophylaxis containing PTCy after allo-HSCT from an unrelated donor does not
have an increased risk in terms of bacterial, viral, or fungal infections and can
be used safely.