Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing.
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/m(2), 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.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Michael B
MB
Maris
Brenda M
BM
Sandmaier
Barry E
BE
Storer
David G
DG
Maloney
Judith A
JA
Shizuru
Edward
E
Agura
Constanze
C
Kliem
Michael
M
Pulsipher
Richard T
RT
Maziarz
Peter A
PA
McSweeney
James
J
Wade
Amelia A
AA
Langston
Thomas R
TR
Chauncey
Benedetto
B
Bruno
Karl G
KG
Blume
Rainer
R
Storb
D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000401:mortality / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019653:Myeloablative Agonists / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D011994:Recombinant Proteins; D012074:Remission Induction; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine