Prognostic importance of structural chromosomal abnormalities in children with hyperdiploid (greater than 50 chromosomes) acute lymphoblastic leukemia

Approximately one fourth of children with newly diagnosed acute lymphoblastic leukemia (ALL) have hyperdiploid (greater than 50 chromosomes) blasts and a relatively favorable prognosis. Nonetheless, a substantial proportion of these patients fail therapy. We studied 138 children (70 male, 68 female) with hyperdiploid greater than 50 ALL to assess initial clinical and cytogenetic features that might predict treatment failure. In 85 of these cases (62%), structural chromosomal abnormalities were also present; clinical and laboratory features in this group did not differ from those of the 53 cases with only numeric abnormalities. However, of the 28 failures seen at a median follow-up of 4 years, 22 occurred in cases with structural chromosomal abnormalities (P = .03 by Breslow test). In a multivariate analysis, only the presence of structural chromosomal abnormalities and male gender were independently associated with treatment failure. Structural chromosomal abnormalities in cases of ALL with greater than 50 chromosomes may define a biologically different form of leukemia characterized by increased likelihood of drug resistance.     

Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia

We studied the presenting clinical and biologic features of 23 children with acute lymphoblastic leukemia (ALL) whose leukemic marrow karyotypes contained abnormalities involving the short arm of chromosome 12. Nineteen of the abnormalities were assigned to the 12p12 breakpoint. The median age of the children was 5 years (range 2 to 13 years) and their initial leukocyte counts ranged from 1,800 to 424,000/microL (median 30,000/microL). Twenty-one patients (91%) had common phenotype ALL (CALLA+, HLA-DR+), including three cases with a pre-B cell phenotype (CIg+). The remaining two cases were T cell in origin. The French-American-British (FAB) morphologic type of lymphoblastic leukemia was L1 in all cases but one. With a median follow-up of 11 months, four patients have relapsed and another failed induction therapy. The modal chromosome number in all cases was less than 50. Three distinct cytogenetic patterns, with apparently similar clinical manifestations, were noted: terminal deletions of chromosome 12 in 10 cases, apparently balanced reciprocal translocations in 6, and unbalanced translocations in 7. All translocations were between the 12p arm and different donor chromosomes except for chromosomes 7, 9, and 17, which participated twice. Only two patients had identical translocations: t(7;12)(q11;p12). This unusual variation in donor chromosomes and breakpoints suggests that translocations involving the 12p are specific with respect to only one member of the translocation pair, namely chromosome 12. The relatively high frequency of the 12p abnormalities in this study (10% of all completely banded cases seen over a 35-month period) warrants further investigation.     

EFFECT OF SUBCLINICAL LEAD INTOXICATION ON LARYNGEAL CANCER

SUMMARY In this study we investigated the possible relationship of laryngeal cancer and subclinical lead intoxication, using the depression of aminolevulinic acid dehydratase (ALAD) activity in blood as indicator. Twenty-six patients with laryngeal cancer and 53 normal controls met the criteria to enter the study. Blood ALAD activity values in the patients with laryngeal cancer ranged from 27.1 to 75.3 U/l with a mean of 50.79 U/l. The respective values in the control group ranged from 36.2 to 98 U/l with a mean of 59.76 U/l. There was a statistically significant difference between the two means (0.001 <p<0.01), whereas blood lead concentrations in all patients were within normal limits. These findings support the hypothesis that low level lead intoxication (subclinical blood lead levels), from cars, industries and products, may contribute to the risk of laryngeal cancer. Further investigation is needed to clarify the exact relationship between lead and cancer of the larynx.