Aage Drivsholm

In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: A cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients

Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12single), 20 as +12 with additional abnormalities (+12complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q. The immunophenotype was typical for CLL in 358 patients (CD5+, Slg(weak), mainly FMC7-) and atypical for CLL in 122 patients (25%) (CD5-, or Slg(strong) or FMC7+). Chromosome abnormalities were found significantly more often in patients with atypical (48%) than in patients with typical CLL phenotype (22%) (P < 0.00005). Also +12complex, 14q+, del6q, and abnormalities of chromosome 17 were significantly more frequent in patients with atypical CLL phenotype, whereas +12single was found equally often in patients with typical and atypical CLL phenotype. The cytomorphology of most of the +12 patients was that of classical CLL irrespective of phenotype. In univariate survival analysis the following cytogenetic findings were significantly correlated to a poor prognosis: chromosome 17 abnormalities, 14q+, an abnormal karyotype, +12complex, more than one cytogenetic event, and the relative number of abnormal mitoses. In multivariate survival analysis chromosome 17 abnormalities were the only cytogenetic findings with independent prognostic value irrespective of immunophenotype. We conclude that in patients with typical CLL immunophenotype, chromosome abnormalities are somewhat less frequent at the time of diagnosis than hitherto believed. +12single is compatible with classical CLL, and has no prognostic influence whereas chromosome 17 abnormalities signify a poor prognosis. In patients with an atypical CLL immunophenotype, chromosome abnormalities including +12complex, 14q+, del 6q and chromosome 17 are found in about 50% of the patients, and in particular chromosome 17 abnormalities suggest a poor prognosis.

Chromosomal banding patterns in 88 cases of acute nonlymphocytic leukemia

Abstract The chromosomal findings in 88 consecutive cases of acute nonlymphocytic leukemia (ANLL) which have been cytogenetically evaluated are reported. The chromosomes were directly prepared from bone marrow cells and studied by trypsin-Giemsa banding. Abnormal stem lines were found in 42% of the cases. Supernumerary chromosomes Nos. 6, 8 and 21, missing chromosomes 7 and Y, and structural rearrangements t(8;21) and 5q—occurred so often that nonrandom events are presumably underlying. It is shown that nonidentical marker chromosomes often have break points in common. Several vulnerable points which particularly often appear to break in structural rearrangements are located. It is pointed out and discussed that the large series of ANLL analysed with banding which have been published so far disagree concerning the frequencies of nonrandom aberrations.

Chromosomes and survival in multiple myeloma. A banding study of 25 cases

Abstract The chromosomal findings in 25 cases of multiple myeloma are reported. The chromosomes were directly prepared from bone marrow cells and studied by trypsin-Leishman banding. Abnormal stem lines were found in 16 cases (64%), and were characterized by banding in 12 cases. Twelve cases were hyperdiploid; 11 cases carried marker chromosomes, 50% of which involved chromosome No. 1. Five cases were trisomic for 1q21-1q3. A vulnerable point was located on 3q27 or 28 or 29. The two cases that carried the 14q+ marker chromosome were also the only cases with plasma cells in the peripheral blood. Based on this study and the literature it is suggested that a 14q+ is necessary for the development of plasma cell leukemia. The actuarial survival curves gave no evidence for major prognostic significance of the demonstration of an abnormal cell clone. Trisomy for 1q21-1q3 may be a bad prognostic sign. The results are discussed with special reference to the aberrations in acute nonlymphocytic leukemia as reported earlier in a series of 88 cases from this laboratory.

Occurrence and type of chromosomal abnormalities in consecutive malignant monoclonal gammopathies: Correlation with survival

Chromosome studies were done on 73 patients with multiple myeloma and three patients with plasma cell leukemia. Eighteen of 76 patients (24%) had chromosomally abnormal clones, including all three patients with PCL. The most common anomalous chromosomes were #1, #14, and #12. In addition, i(17q) was found in two patients with plasma cell leukemia. Among newly diagnosed patients there was no difference in survival for those with abnormal karyotypes and those with normal karyotypes. Among previously diagnosed patients receiving treatment, however, individuals with an abnormal clone had a significantly higher mortality during the first 2 years compared to those with a normal clone. Patients with no growth of metaphases in their bone marrow aspirate had a significantly lower mortality than other patients (p less than 0.05).

Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia

Aberrations of chromosome 6 were observed in 11 of 193 cases of chronic lymphocytic leukemia diagnosed January 1, 1984-November 1, 1988 and investigated cytogenetically within 30 days after diagnosis. The 6p was rearranged in 5 cases: 4 balanced and 1 unbalanced translocation. The 6q was involved in 6 cases: 4 deletions and 2 balanced translocations. Three of the del(6q) may be identical: del(6)(q13q27). In two cases there were no additional aberrations. Aberrations of chromosome 6 correlated significantly with an advanced clinical stage, diffuse pattern of bone marrow infiltration, and increased SmIgM-fluorescence intensity. All these factors are associated with poor prognosis. Although the number of cases with 6q aberrations is still too small and the observation period too short to show significant influence on survival, the presence of 6q aberrations at diagnosis may prove useful in delineating a subtype of chronic lymphocytic leukemia with poor prognosis.