Differences in bone marrow cytogenetic characteristics between treated and untreated myeloma

Abstract

Clonal karyotypic abnormalities in myelomatosis at initial diagnosis have been widely studied, but little data are available on the karyotypic status following treatment. We have studied bone marrow (BM) from 17 cases of untreated myelomatosis at initial diagnosis and from a further 29 cases who had received chemotherapy with regimens containing alkylating agents. At the time of study all previously treated cases had been off treatment for at least 152 days, had a paraprotein level in plateau phase, had a BM with less than 4% blasts, and in 28 of these 29 cases had less than 20% BM plasma cells. Two cases had more than 15% BM ringed sideroblasts; one other case was transfusion dependent.Clear differences in cytogenetic characteristics between the two groups were seen. At initial diagnosis clonal karyotypic abnormalities were observed in six of 11 assessible cases. All had hyperdiploid clones (of 49–54 chromosomes) and showed characteristic involvement of chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. Additional structural rearrangements were present in only two of these cases. Following treatment, clonal abnormalities were seen in 10 of 25 assessible cases, of which only two showed hyperdiploidy (one with a hyperdiploid line, one with an additional derived chromosome). The remaining eight showed hypodiploid or pseudodiploid lines, and seven of these showed complex karyotypes with multiple rearrangements particularly affecting chromosomes 1, 2, 3, 6 and 7. After a minimum follow-up of 16 months, only four of these 10 cases (40%) remain alive compared with 12 of 15 (80%) with a normal karyotype after treatment (P = 0.03). No correlation was observed between the presence of an abnormal karyotype and the total dose or timing of previous therapy, though cases with an abnormal karyotype tended to have received treatment for longer (790 ± 166 days) than cases with a normal karyotype (486 ± 50 days). It is not clear whether the ploidy difference between the two groups represents a change in the disease state due to treatment or a direct effect of treatment itself.