Incidence of Invasive Fungal Infection (IFI) after Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) for Adult Patients with Hematological Diseases.

Introduction

Cord blood is an alternative stem cell source, and RICBT is investigated as a clinical trial. High incidence of infection is an obstacle to the spread of RICBT; however, the detail of infectious complication is not described. We retrospectively investigated the incidence and risk factor of IFI after RICBT.

Patient and method

A total of 102 patients received RICBT at Toranomon Hospital from March 2002 to May 2004. The median age of the patients was 57 years (range, 20–79). Underlying diseases included acute myeloid leukemia or myelodysplastic syndrome (n = 43), malignant lymphoma (n = 38), acute lymphoblastic leukemia (n = 12), multiple myeloma (n = 4), severe aplastic anemia (n = 3), chronic myeloid leukemia (n = 1) and idiopathic myelofibrosis (n = 1), and 90 (88%) patients had advanced or chemorefractory diseases. Preparative regimen comprised fludarabine 125mg/m², melphalan 80 mg/m² and 400 cGy total body irradiation. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n = 80) or tacrolimus (n = 22). The median number of infused nucleated cell was 2.8 (range, 2.0 – 4.6) x 10E7 cells / kg, and HLA disparity was 0 (n = 1), 1 (n = 15) and 2 (n = 86). Patients were managed in laminar airflow-equipped rooms. All patients received fluconazole 200 mg/day for the prophylaxis of fungal infection. Proven or probable invasive fungal infections were defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC / MSG) criteria. Patients with possible IFI were not included in this analysis. The day of diagnosis of the fungal infection was the day on which the first positive diagnostic test was performed. For patients whose diagnosis was established after death, the date of death was considered to be the day of diagnosis.

Result

The median follow-up after RICBT was 8.5 months (range, 0.9–28). Eighty patients achieved primary engraftment, and the median time to engraftment was 20 days (range, 9–55). Nine (9%) patients developed IFI (Aspergillosis 8, Trichosporosis 1). Two patients had a history of IFI prior to transplant. The median time of diagnosis was 15 (range, 2–179) days after transplant. Six of the nine IFI developed during neutropenia. Four patients responded to treatment with amphotericin B and micafungin, and five patients died of IFI. No risk factor was identified in univariate and multivariate analysis.

Discussion

Different from recent reports on IFI after nonmyeloablative transplantation from adult donor, IFI develops early after RICBT. Because most of patients received multiple courses of myelosuppressive chemotherapy, patients possibly had latent IFI. In fact, two patients with history of IFI recurred after RICBT. Moreover, most of patients developed IFI in laminar-airflow equipped room. These facts suggest that early onset IFI might be an activation of latent fungal infection. On the other hand, increased incidence of bacterial and viral infection suggests the possibility that profound immunosuppression after RICBT causes early onset IFI.

Conclusion

IFI develops during neutropenia in RICBT. Prospective study to evaluate the risk factor of IFI and the effective fungal prophylaxis for RICBT is warranted.