MARROW TRANSPLANTATION FOR CHRONIC MYELOID-LEUKEMIA - THE INFLUENCE OF PLASMA BUSULFAN LEVELS ON THE OUTCOME OF TRANSPLANTATION

The influence of busulfan (BU) plasma concentration on outcome of tran splantation from HLA identical family members for the treatment of chr onic myelogenous leukemia (CML) was examined in 45 patients transplant ed in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). A ll patients received the same regimen of BU, 16 mg/kg orally and cyclo phosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (CssBU) during the dosing interval were measured for each patient. The mean CssBU was 917 ng/mL (range, 642 to 1,749; media n, 917; standard deviation, 213). Of patients with CssBU below the med ian, seven (five of 18 in CP and two of four in AP) developed persiste nt cytogenetic relapse and three of these patients died. There were no relapses in patients with CssBU above the median. The difference in t he cumulative incidence of relapse between the two groups was statisti cally significant (P = .0003). CssBU was the only statistically signif icant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with Cs sBU above and below the median (P = .33). There was no statistically s ignificant association of CssBU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 an d 0.64 was only 0.24, similarly CssBU above the median was not associa ted with an increased risk of severe regimen-related toxicity. We conc lude that low BU plasma levels are associated with an increased risk o f relapse. (C) 1997 by The American Society of Hematology.