title: Targeted busulfan and cyclophosphamide as compared to busulfan and TBI as preparative regimens for transplantation in patients with advanced MDS or transformation to AML.
abstract: Hematopoietic cell transplantation is the only curative therapy for patients with myelodysplasia (MDS). However, treatment-related toxicity and, in patients with advanced MDS (RAEB, RAEB-T) and those who have transformed to AML (tAML), post-transplant relapse continues to be problematic. We reviewed results in 128 patients with advanced MDS and tAML transplanted from HLA-identical related or unrelated donors after preparation with myeloablative conditioning regimens. Seventy-eight patients were conditioned with busulfan (Bu), prescribed dose 16 mg/kg, adjusted to achieve plasma concentrations of 800-900 ng/ml, plus cyclophosphamide (Cy), 2 x 60 mg/kg [tBuCy], and 50 patients were conditioned with Bu 7 mg/kg (without dose adjustment) and total body irradiation (TBI) 6 x 200 cGy given over 3 days [BuTBI]. There was no statistically significant difference in regards to overall survival, relapse-free survival (RFS), or non-relapse mortality (NRM) between the 2 regimens regardless of donor status. However, there was a trend towards higher rates of relapse (HR 1.33, P=0.38) and lower rates of NRM (HR 0.61, P=0.09) in patients conditioned with tBuCy. The increased rate of relapse seen with tBuCy was significant when restricted to only those patients with a diagnosis of RAEB (HR 4.50, P=0.02). Patients given BuTBI had a higher incidence of GvHD; however, the incidence of GvHD regardless of grade did not differ significantly between patients who relapsed and those who did not. Thus, in patients with advanced MDS/tAML, the use of a less toxic conditioning regimen resulted in a non-significant overall gain in RFS largely due to lower rates of NRM. New concepts of conditioning regimens are needed which reduce toxicity without increasing the risk of relapse.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. bscott@fhcrc.org
authors.forename: Bart
authors.initials: B
authors.lastname: Scott
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Stephen
authors.initials: S
authors.lastname: Petersdorf
authors.forename: John
authors.initials: J
authors.lastname: Slattery
authors.forename: Frederick
authors.initials: F
authors.lastname: Appelbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D012008:Recurrence; D015996:Survival Rate; D019172:Transplantation Conditioning
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan