Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. Clinical and cytogenetic characteristics and results of in vitro culture of bone marrow and HLA typing

Thirty-one patients were studied with a clinical picture of preleukemia, acute myeloproliferative syndrome, or overt acute nonlymphocytic leukemia following irradiation and/or chemotherapy for lymphoproliferative disorders, multiple myeloma, or solid tumors. In 28 patients the original tumor was in complete remission. All patients had developed leukocytosis or unexplained cytopenia. The initial examinations disclosed overt acute nonlymphocytic leukemia in 5, acute myeloproliferative syndrome in 5, and preleukemia in 21 patients. During the follow-up period, acute myeloproliferation or overt leukemia developed in 16/21 preleukemic patients. Clonal cytogenetic abnormalities in the bone marrow were observed in 26/31 patients, 21 were hypodiploid, and all abnormal clones apparently were lacking a B or C group chromosome. Banding technique disclosed the abnormality as 5q– in four, – 5 in one.–7 in seven, and the combination of 5q– and –7 in four cases. Isolated defects of other B or C group chromosomes were not observed. In vitro culture of the bone marrow in agar was abnormal on day 7 in 20/22 patients examined. Absent growth of colonies was the most characteristic finding observed in 18 patients; other abnormalities were reduced or increased growth of clusters and growth of microclusters. The distribution of blood types and HLA types in the patients was random, except for a possibly increased incidence of HLA-B27. A major group of patients developed cytopenia with the cytogenetic abnormalities 5q– and/or –7, alternatively–B and/or –C in bone marrow cells 30–60 mo from start of treatment with an alkylating agent. Most of these patients subsequently showed further leukemic evolution and could represent cases of therapy-induced leukemias.