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Analyses of bone marrow blast cells collected at diagnosis and relapse from 68 children with acute lymphoblastic leukemia (ALL) demonstrated changes in the expression of cell markers in one-fourth of the patients. Loss of the common ALL antigen (CALLA) was a frequent change, occurring in 8 of the 51 cases initially classified as common or pre-B ALL. The HLA-DR antigen was either acquired or lost in 5 of the 68 cases, terminal deoxynucleotidyl transferase was lost in 6 of 25 cases, and reactivity of the T10 antigen with monoclonal antibodies was increased in 6 of 17 cases of non-T cell ALL. Conversion to acute nonlymphoblastic leukemia, so-called lineage switch, was noted in two cases of common ALL and one of pre-B ALL, coinciding with the loss of CALLA. Results of chromosomal analyses in cases with a loss of CALLA implicated several mechanisms in the observed phenotypic changes. In six cases, including each instance of lineage switch, the original karyotype had been replaced by an entirely different abnormal karyotype, suggesting clonal selection or induction of a second malignancy. In another case, the evidence suggested clonal evolution. Our findings demonstrate that sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanisms of leukemic recurrence and may have implications for treatment selection.

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.

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.