Chromosomal changes in secondary leukemias of childhood and young adulthood

The increasing success of antineoplastic therapy has resulted in a growing number of long-term survivors. These people are at risk for complications of the therapy itself. Among these induced acute nonlymphoid leukemia (ANLL) has been both common and often lethal. We reviewed 72 recently reported patients under 30 years of age at the time of initial diagnosis who developed a secondary, karyotypically defined leukemia. Fifty-eight patients contracted ANLL a mean of 4 1/2 years from the initial diagnosis. In 25 patients, this was preceded by a preleukemic phase characterized by a hypercellular bone marrow with abnormal precursors, often accompanied by peripheral pancytopenia, that lasted a mean of 6 months. Three additional patients died in this preleukemic phase. In all 61, the most common chromosomal abnormalities were numerical errors. Twenty-four patients had a hypodiploid karyotype, most often in those in whom the primary diagnosis was lymphoma (22 of 43). The most common chromosomes missing in whole or in part were number 7 (18 patients), number 5 (8 patients), number 17 (5 patients), and number 21 (4 patients). The anomalies were frequently multiple and complex. Monosomy 7 figured particularly strongly and may be similar to a karyotypically identical myeloproliferative disorder characterized by micromegakaryocytes, giant platelets, and abnormal granulocyte function arising de novo in children. These findings are similar to those in older patients with ANLL induced by environmental carcinogens or antineoplastic therapy. They are different from the karyotypic changes seen in de novo ANLL in children and young adults, suggesting a different etiology. Also, they reinforce the need to find less leukemogenic treatment programs.