Cytogenetic analysis was performed in 47 newly diagnosed patients with agnogenic myeloid metaplasia (AMM); 32 had a normal karyotype (68%, group I), whereas 15 had clonal abnormalities (32%, group II). The most frequent abnormal findings were a 20q- deletion in six cases (either alone or within complex anomalies), interstitial 13q- deletion in three cases (and monosomy 13 in one case), and acquired trisomy 21 or 21p+ in three cases. Four cases exhibited complex aberrations involving several chromosomes, sometimes with a mosaicism. In two patients with an initial abnormal karyotype, further cytogenetic analysis during the disease course showed the appearance of additional clonal anomalies, and particularly of a probable Philadelphia (Ph1) variant in one case. Treatment was essentially supportive. Survival was significantly shorter in group II (median, 30 months) compared with group I (median, not reached at 6 years; P = .015). In univariate analysis, other parameters significantly associated with a poor prognosis (P less than .05) were higher age, anemia, and increased percentage of circulating blasts. However, in a multivariate analysis, only cytogenetic abnormalities and age retained their independent prognostic value.

Cytogenetic analysis was performed in 47 newly diagnosed patients with agnogenic myeloid metaplasia (AMM); 32 had a normal karyotype (68%, group I), whereas 15 had clonal abnormalities (32%, group II). The most frequent abnormal findings were a 20q- deletion in six cases (either alone or within complex anomalies), interstitial 13q- deletion in three cases (and monosomy 13 in one case), and acquired trisomy 21 or 21p+ in three cases. Four cases exhibited complex aberrations involving several chromosomes, sometimes with a mosaicism. In two patients with an initial abnormal karyotype, further cytogenetic analysis during the disease course showed the appearance of additional clonal anomalies, and particularly of a probable Philadelphia (Ph1) variant in one case. Treatment was essentially supportive. Survival was significantly shorter in group II (median, 30 months) compared with group I (median, not reached at 6 years; P = .015). In univariate analysis, other parameters significantly associated with a poor prognosis (P less than .05) were higher age, anemia, and increased percentage of circulating blasts. However, in a multivariate analysis, only cytogenetic abnormalities and age retained their independent prognostic value.

Cytogenetic analysis was made at diagnosis in 174 cases of ALL (101 children less than 20 years and 73 adults), excluding Burkitt's ALL (L3). In 11 children (11 per cent) insufficient material was obtained. In the remaining 90, 50 (56 per cent) had a normal karyotype, 20 (22 per cent) a hyperdiploid karyotype, five (6 per cent) a hypodiploid karyotype, 12 (13 per cent) had a translocation (including seven cases of t(1;19] and three had a pseudodiploid karyotype without translocation. Ninety-eight per cent of patients reached complete remission (CR). Median actuarial CR duration was not attained, was 50 months, 13 months, and 11 months respectively in patients with hyperdiploid, normal, hypodiploid karyotype and in patients with a translocation, the difference between subgroups being significant. In a Cox model, cytogenetics were the strongest factor predicting CR duration (p = 0.03) followed by leukocytes (p = 0.04), whereas the presence of 'bulky disease' had a borderline value (p = 0.077). Of note was that 9/17 (53 per cent) patients with a hypodiploid karyotype or a translocation had no 'risk factors' before cytogenetic analysis. In adults, cytogenetic analysis was unsuccessful in 15 (20 per cent) of patients. In the remaining 58 cases, 19 (33 per cent) had a normal karyotype, 15 (26 per cent) had a hyperdiploid, one (2 per cent) had a hypodiploid karyotype, 19 (33 per cent) had a translocation (including 12 t(9;22], and four (7 per cent) had a pseudodiploid without translocation. 73 per cent patients reached CR. Median actuarial DFS was 12.5 months. No significant differences in CR rate and CR duration were seen between cytogenetic groups, but median CR duration was slightly longer in patients with a normal karyotype (17 months) and shorter in patients with t(9;22) (8.5 months). Only 3/12 of the latter had major risk factors before cytogenetic analysis. Cytogenetic analysis is important in ALL, especially in patients with otherwise standard risk factors, as it may reveal unexpected translocations or hypodiploidy, which may require a therapeutic reinforcement.

In a well-documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6-12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV-induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision-repair defect of 9.2-13.5 per cent of residual activity.

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