Methods Of Sct Myeloablative regimens

A number of myeloablative regimens have been used for SCT in AML. The two most common were derived

Table 35.2 Risk stratification of acute myeloid leukemia Favorable

Age <60 WBC <100,000 De novo leukemia t(15;17); t(8;21); inv16 (or t(16;16))

absence of high risk cytogenetic abnormalities or FLT3-ITD

Unfavorable

Antecedent hematologic condition (e.g., myelodysplasia) or prior chemotherapy/radiation

Deletions/monosomies of chromosome 3, 5, 7, or complex karyotype (>3 per SWOG or >5 per MRC), t6;9, 11q23 rearranged FLT3-ITD

Intermediate/indeterminate all others

SWOG: Southwest Oncology Group; MRC: Medical Research Council (United Kingdom); FLT3-ITD: /ms-like tyrosine kinase 3-internal tandem duplication mutation.

by the pioneering work in AML by the Seattle and Johns Hopkins groups. To this day, total body irradiation (TBI) and cyclophosphamide (Cy) or the busulfan (Bu) and Cy, are the most common regimens utilized. Traditional Bu/Cy consists of 1 mg/kg oral Bu given every 6 h for 16 total doses (16 mg/kg), followed by 2-4 days Cy for a total of 120-200 mg/kg. Most centers utilize the Bu/Cy (2) regimen, as comparison between it and Bu/Cy (4) has shown reduced toxicity for BuCy

(2) without an impact on efficacy. Recently, Bu dosing has been guided and adjusted pharmacokinetically by measuring area under the curve (AUC) to correct for erratic GI absorption and first-pass hepatic metabolism. Maintenance of steady-state Bu levels within a narrow range seems to reduce toxicity, particularly hepatic veno-occlusive disease. More recently, an intravenous formulation of busulfan has become available, with the benefit of far more predictable pharma-cokinetics, minimal patient to patient variability, and potentially less toxicity. The most common radiation-containing preparative regimen for autografting is 120 mg/kg Cy with six fractionated doses of 200 cGy. No definitive data suggest a clear benefit of a radiation-containing regimen over a CT regimen.

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