Targeted busulfan and cyclophosphamide as compared to busulfan and TBI as preparative regimens for transplantation in patients with advanced MDS or transformation to AML.
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.
Scott
Bart
B
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. bscott@fhcrc.org
Deeg
H Joachim
HJ
Storer
Barry
B
Chauncey
Thomas
T
Petersdorf
Stephen
S
Slattery
John
J
Appelbaum
Frederick
F
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
D003520:Cyclophosphamide; D002066:Busulfan