Unrelated Donor Granulocyte Colony-Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cell Transplantation after Nonmyeloablative Conditioning: The Effect of Postgrafting Mycophenolate Mofetil Dosing

Autor: Edward Agura, Brenda M. Sandmaier, Barry E. Storer, Peter A. McSweeney, David G. Maloney, Richard T. Maziarz, Karl G. Blume, Rainer Storb, Michael B. Maris, Benedetto Bruno, Amelia Langston, Thomas R. Chauncey, Constanze Kliem, Michael A. Pulsipher, James C. Wade, Judith A. Shizuru
Rok vydání: 2006
Předmět:
Graft Rejection
Male
Hematologic malignancy
Transplantation Conditioning
medicine.medical_treatment
Graft vs Host Disease
Gastroenterology
0302 clinical medicine
Unrelated donor allografting
Granulocyte Colony-Stimulating Factor
Nonmyeloablative conditioning
Hematopoietic cell transplantation
Graft Survival
Remission Induction
Immunosuppression
Hematology
Middle Aged
Total body irradiation
Recombinant Proteins
3. Good health
Fludarabine
Granulocyte colony-stimulating factor
Survival Rate
Hematologic Neoplasms
030220 oncology & carcinogenesis
Cyclosporine
Female
Immunosuppressive Agents
Vidarabine
medicine.drug
Adult
medicine.medical_specialty
Graft-versus-tumor effect
Adolescent
Peripheral blood mononuclear cell
Disease-Free Survival
Mycophenolic acid
03 medical and health sciences
Pharmacokinetics
Internal medicine
medicine
Humans
Aged
Peripheral Blood Stem Cell Transplantation
Transplantation
business.industry
Mycophenolic Acid
Myeloablative Agonists
Surgery
Reduced-intensity conditioning
business
030215 immunology
Zdroj: Biology of Blood and Marrow Transplantation. 12(4):454-465
ISSN: 1083-8791
DOI: 10.1016/j.bbmt.2005.12.030
Popis: 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.
Databáze: OpenAIRE
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