Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis

Abstract

Summary:In a 10-year consecutive series of 263 allogeneic bone marrow transplant recipients, we identified five cases (1.9%) of invasive mucormycosis. Only one infection occurred within the first 100 days after transplantation, while the remainder complicated the late post-transplant course (median day of diagnosis: 343). Sites of infection were considered 'non-classical' and included pulmonary, cutaneous and gastric involvement. No case of fungal dissemination was observed. Mucormycosis was the primary cause of death in three of the five patients. Corticosteroid-treated graft-versus-host disease, either acute or chronic, or severe neutropenia were present in all cases. However, compared with a matched control population, the most striking finding was the demonstration of severe iron overload in each of the mucormycosis patients. The mean level of serum ferritin, transferrin saturation and number of transfused units of red cells (2029 g/l, 92% and 52 units, respectively) in the study group is significantly higher compared with the control group (P Ͻ 0.05). The difference with other risk groups for mucormycosis, including deferoxamine-treated dialysis patients and acidotic diabetics, was analyzed in view of the possible pathogenic role of iron. Although these infections are often fatal, limited disease may have a better prognosis if diagnosed early and treated aggressively.

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation

“…12 An increase in some late fungal infections, specially mucormycosis, have been reported in iron loaded patients after HSCT. 13 Further studies to confirm our findings are mandatory. If these results are reproduced, pre-transplant strategies to decrease iron overload 14 could be proposed to decrease TRM and improve survival.…”

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

“…26 Interestingly, previous clinical papers have related iron overload and infection in immuno-deficient patients, and the infection was always produced by Aspergillus or Mucor. [27][28][29] In our series, Aspergillus infection was not related with neutropenia or acute GVHD, probably because 41% of cases were autologous transplants and the number of patients with long-standing neutropenia or severe acute GVHD was low. An association between CMV disease and fungal infections has been noted not only in solid organ transplant recipients 30,31 but also in recipients of HSCT.…”

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

“…There is a positive correlation between iron overload and infectious events in both allogeneic and autologous hematopoietic stem cell transplantation. Among these infections, bacteremia, invasive aspergillosis and mucormycosis are the most prevalent [18].…”