Reduced Intensity Cord Blood Transplantation Using Mycophenolate Mofetil and Cyclosporine for Adult Patients with Advanced Hematologic Malignancies.

Objectives: To evaluate the feasibility of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) using cyclosporine and mycofenolate mofetil as graft-versus-host disease (GVHD) prophylaxis for adult patients with advanced hematological diseases

Methods: Twenty-one patients (median age, 54; range, 30–76) with advanced hematological diseases underwent RI-UCBT at Metropolitan Fuchu Hospital between July 2002 and September 2004. Underlying disease included AML (n=7), non-Hodgkin lymphoma (n=10), Hodgkin lymphoma (n=2), and aplastic anemia (n=1). Preparative regimen comprised fludarabine (Flu) and total body irradiation (TBI), combined with busulfan (BU) or cyclophosphamide (CY). GVHD prophylaxis was cyclosporine and mycophenolate mofetil. Primary endpoint of this study was engraftment. Secondary endpoints were to describe clinical features of immune reactions following RI-CBT. Immune reactions included high-grade fever (> 38 degree centigrade), elevation of serum C-reactive protein (CRP) levels, skin rash or erythema, diarrhea, hyperbilirubinemia, symptoms of central nerve systems, and body weight gains. They were classified according to their onset after transplant: pre-engraftment immune reactions, engraftment syndrome, and GvHD.

Results: Ten patients achieved primary neutrophil engraftment at a median of day 22 (range, 11–33). Five patients died of disease progression before engraftment. Primary graft failure was diagnosed in the remaining 6 patients. Among them, 3 patients received second transplant, and the other 3 patients developed autologous hematopoiesis recovery. Seven of 10 patients who achieved engraftment developed pre-engraftment immune reactions including fever, an increase in CRP, skin rash, diarrhea, and body weight gain. Similar manifestations were observed in six patients who had not achieved primary engraftment. Six patients developed engraftment syndrome. Nine patients developed Grade II to IV GVHD: skin rash (n=9), diarrhea (n=7), and hyperbilirubinemia (n=1). Seven of 10 patients who achieved engraftment survived without disease progression at a median follow-up of 17.5 months (range, 8.4–29.0).

Conclusions: This study demonstrated the feasibility of RI-UCBT in adults, indicating that acute GVHD prophylaxis with cyclosporine and mycophenolate mofetil is worth considering for further intense evaluation.