Busulfan/Cytoxan and Busulfan/Fludarabine induction in BMT – pro
Two combinations are well established as preparative regimens for leukemia: cyclophosphamide (Cytoxan, Neosar) plus total-body irradiation (TBI) or busulfan (Myleran) plus cyclophosphamide. TBI has been given as a single dose in the past, but a high incidence of complications, especially interstitial pneumonitis, occurred. Fractionated TBI with lung shielding in combination with cyclophosphamide, 60 mg/kg/d intravenously (IV) for 2 days, has been found to provide adequate antileukemic activity with acceptable toxicity. Fractionation schedules vary and may affect the outcome. Hyperfractionation of TBI also has been investigated, with no apparent benefit reported to date.
Busulfan is administered orally at a dose of 1 mg/kg every 6 hours for 16 doses followed by four doses of cyclophosphamide, 50 mg/kg, or two doses at 60 mg/kg. Randomized studies comparing these drug regimens have not been performed, and it is unclear whether either regimen is significantly better than the other with regard to efficacy or toxicity. Busulfan/cyclophosphamide has been compared with cyclophosphamide/TBI in randomized studies, but the results remain controversial.
I reference two older studies that established this regimen as the default in bone marrow transplantation and a PDF 2003 of the current status of this regimen.
Busulfan/fludarabine is a regimen that is in trials, for example, Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers, NCT00619645. This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.
Blaise D, Maraninchi D, Archimbaud E, et al: Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: A randomized trial of busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: A report from the Groupe d’Etudes de la Greffe de Moelle Osseuse. Blood 79:2578, 1992.
http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.med.54.101601.152456
Borje S. Andersson, Marcos de Lima, Peter F. Thall, Xuemei Wang, Daniel Couriel, Martin Korbling, Soonja Roberson, Sergio Giralt, Betty Pierre, James A. Russell, Elizabeth J. Shpall, Roy B. Jones and Richard E. Champlin Once Daily i.v. Busulfan and Fludarabine (i.v. Bu-Flu) Compares Favorably with i.v. Busulfan and Cyclophosphamide (i.v. BuCy2) as Pretransplant Conditioning Therapy in AML/MDS Biology of Blood and Marrow Transplantation, Volume 14, Issue 6, June 2008, Pages 672-684