title: Administration and pharmacokinetics of high-dose cyclophosphamide with hemodialysis support for allogeneic bone marrow transplantation in acute leukemia and end-stage renal disease.
abstract: We report a patient with pre-existing end-stage renal disease (ESRD) who underwent successful matched related donor allogeneic bone marrow transplantation for AML in second complete remission (CR2) using conditioning with high-dose cyclophosphamide (CY, 60 mg/kg/day x 2) and TBI (165 cGy twice daily x 4 days). The timing of hemodialysis after high-dose CY was extrapolated from available data on the pharmacokinetics of high-dose CY and hemodialysis clearance of conventional dose CY and its metabolites. Pharmacokinetic analyses indicated that the elimination of high-dose CY and its alkylating metabolites is impaired in ESRD but is cleared with hemodialysis. The patient's early post-transplant course was uncomplicated, and WBC and platelet engraftment occurred by day +22. Bone marrow examination on day +25 showed trilineage engraftment with no AML; cytogenetics showed 100% donor karyotype. The patient remains in remission with 100% donor karyotype at 3 years post transplant. Clinical results indicate that the administration of high-dose CY is feasible with hemodialysis support for patients with ESRD.
authors.affiliation: Comprehensive Cancer Center of Wake Forest University, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Perry
authors.forename: R A
authors.initials: RA
authors.lastname: Fleming
authors.forename: M V
authors.initials: MV
authors.lastname: Rocco
authors.forename: W P
authors.initials: WP
authors.lastname: Petros
authors.forename: A J
authors.initials: AJ
authors.lastname: Bleyer
authors.forename: J E
authors.initials: JE
authors.lastname: Radford
authors.forename: B L
authors.initials: BL
authors.lastname: Powell
authors.forename: D D
authors.initials: DD
authors.lastname: Hurd
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D006435:Renal Dialysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D003520:Cyclophosphamide