Secondary acute myeloid leukemia with inv(16): report of two cases following paclitaxel-containing chemotherapy and review of the role of intensifiedara-C therapy

Acute myeloid leukemia developing secondary to prior cytotoxic chemotherapy (s-AML) encompasses a range of distinct entities. We report two cases of s -AML with inv(16)(p13q22) who had prior exposure to paclitaxel. Additionall y, two previously reported cases of s-AML with inv(16) had prior paclitaxel exposure raising the possibility that the taxanes may predispose to this s pecific syndrome of s-AML, One of our patients received escalated-dose ara- C chemotherapy, achieving a complete remission (12+ months). We therefore e xamined the prognosis of previously reported cases of s-AML with inv(l6) an d analyzed the influence of escalated-dose ara-C (greater than or equal to 400 mg/m(2)/day). A total of 25 evaluable cases were identified, with 96% a ttaining CR independent of ara-C dose. The estimated median remission durat ion was 40 months and the median survival has not been reached (actuarial B -year survival 52 +/- 18%), Although not achieving statistical significance , patients treated with escalated dose ara-C (n =15) had longer remission d uration and overall survival than those treated with standard dose ara-C (n = 10)(P = 0.063 and 0.20, respectively). In univariate analysis, younger a ge, male gender, and the presence of additional cytogenetic abnormalities w ere associated with a tendency towards adverse outcomes (P < 0.1). Age and gender were equally distributed between ara-C dose cohorts, but more patien ts treated with standard-dose ara-C had additional cytogenetic abnormalitie s (P = 0.048), Within the limitations of this retrospective study, this ana lysis suggests that, similar to de novo AML with inv(16), secondary cases m ay also potentially benefit from treatment with escalated-dose ara-C. This is consistent with the premise that the underlying molecular defect, rather than the presence of prior cytotoxic drug exposure, may be the most import ant determinant of disease behavior and chemotherapy responsiveness in AML.