Acute leukemia treated with intensive chemotherapy in patients with a history of previous chemo- and/or radiotherapy: prognostic significance of karyotype and preceding myelodysplastic syndrome. Groupe Francais de Cytogénétique Hématologique (GFCH)

Abstract

The prognostic significance of karyotype and of a preceding myelodysplastic syndrome (MDS) was evaluated in 57 patients with acute leukemia (AL) treated with intensive chemotherapy. All patients had a history of previous chemo- and/or radiotherapy for a neoplastic disease. Acute nonlymphocytic leukemia (ANLL) was diagnosed in 49 patients, six patients suffered from acute lymphatic leukemia (ALL) and one patient from biphenotypic and undifferentiated AL, respectively. Chromosomal aberration rate was 91%. In 54% of the patients, simple or specific chromosomal anomalies with not more than three cytogenetic defects were found, such as t(8;21), t(15;17), inv(16), t(9;11) and t(4;11). Only 37% of the patients had a karyotype highly characteristic of sAL with more than 4 structural cytogenetic defects, and/or -5, 5q-, -7, 7q-. This unusual distribution of cytogenetic defects in these patients is undoubtedly due to patient selection, since only patients who received aggressive chemotherapy were included in this study. 25 patients had previously been diagnosed as having MDS. Presence or absence of a preceding MDS and karyotype were predictive parameters for achievement of complete remission (CR). CR was obtained in 47% of the patients with normal karyotype or simple aberrations, but only in 24% of the patients with complex anomalies (p = 0.09). Patients without a prior MDS had a higher CR rate (53%) than patients with a preceding MDS (20%) (p = 0.02). CR rate was highest in patients with a normal karyotype or simple aberrations without previous MDS (56%), compared to those with complex anomalies and a prior MDS (14%) (p = 0.02). We conclude that, from a clinical point of view, AL in the former patients should be considered as de novo AL and not as secondary, therapy-related AL and that therapeutic nihilism is no longer justified in these patients.