Haemopoietic Cell Transplantation of Patients with a History of Deep or Invasive Fungal Infection during Prophylaxis with Liposomal Amphotericin B

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the ‘proven’ group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients.

[1]  M. Territo,et al.  Intravenous and Oral Itraconazole versus Intravenous and Oral Fluconazole for Long-Term Antifungal Prophylaxis in Allogeneic Hematopoietic Stem-Cell Transplant Recipients: A Multicenter, Randomized Trial , 2003, Annals of Internal Medicine.

[2]  C. Beyan,et al.  Itraconazole is not effective for the prophylaxis of fungal infections in patients with neutropenia , 2003, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[3]  Richard Sylvester,et al.  Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. , 2002, The New England journal of medicine.

[4]  Lawrence Corey,et al.  Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  D. Denning,et al.  Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  W. Siegert,et al.  A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome , 2001, Bone Marrow Transplantation.

[7]  J. Latgé,et al.  Aspergillus fumigatus and Aspergillosis , 1999, Clinical Microbiology Reviews.

[8]  N. Kröger,et al.  Early infections in patients undergoing bone marrow or blood stem cell transplantation – a 7 year single centre investigation of 409 cases , 1999, Bone Marrow Transplantation.

[9]  J. Latgé,et al.  Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  N. Kröger,et al.  Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia , 1998, Bone Marrow Transplantation.

[11]  D. De Bacquer,et al.  Impact of previous aspergillosis on the outcome of bone marrow transplantation. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  N. Kröger,et al.  High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  M. Kletzel,et al.  Prior fungal infection is not a contraindication to bone marrow transplant in patients with acute leukemia. , 1997, Medical and pediatric oncology.

[14]  P. Ljungman,et al.  Aspergillosis prior to bone marrow transplantation. Infectious Diseases Working Party of the EBMT and the EORTC Invasive Fungal Infections Cooperative Group. , 1995, Bone marrow transplantation.

[15]  J. Esteve,et al.  [Intravenous amphotericin B as prevention of deep mycoses in allogeneic bone marrow transplantation]. , 1994, Medicina clínica (Ed. impresa).

[16]  S. Brunet,et al.  Successful bone marrow transplantation in patients with previous invasive fungal infections: report of four cases. , 1994, Bone marrow transplantation.

[17]  M G Rinaldi,et al.  Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. , 1991, The New England journal of medicine.