TY - JOUR
T1 - Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning
T2 - The effect of postgrafting mycophenolate mofetil dosing
AU - Maris, Michael B.
AU - Sandmaier, Brenda M.
AU - Storer, Barry E.
AU - Maloney, David G.
AU - Shizuru, Judith A.
AU - Agura, Edward
AU - Kliem, Constanze
AU - Pulsipher, Michael
AU - Maziarz, Richard T.
AU - McSweeney, Peter A.
AU - Wade, James
AU - Langston, Amelia A.
AU - Chauncey, Thomas R.
AU - Bruno, Benedetto
AU - Blume, Karl G.
AU - Storb, Rainer
PY - 2006/4
Y1 - 2006/4
N2 - We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m2, 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.
AB - We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m2, 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.
KW - Graft-versus-tumor effect
KW - Hematologic malignancy
KW - Hematopoietic cell transplantation
KW - Nonmyeloablative conditioning
KW - Reduced-intensity conditioning
KW - Unrelated donor allografting
UR - http://www.scopus.com/inward/record.url?scp=33644883417&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644883417&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2005.12.030
DO - 10.1016/j.bbmt.2005.12.030
M3 - Article
C2 - 16545729
AN - SCOPUS:33644883417
SN - 1083-8791
VL - 12
SP - 454
EP - 465
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -