Impact of treatment efficacy on the prognostic value of glucocorticoid receptor levels in childhood acute lymphoblastic leukemia

Glucocorticoid receptor (GR) levels were quantitated in leukemic blasts from bone marrow aspirates of 249 children with acute lymphoblastic leukemia (ALL) who were entered on two St. Jude Total Therapy Studies. Of these, 235 were evaluable for analysis of the relation of GR levels to clinical outcome. For the 42 patients in the earlier Total Therapy Study IX, lower GR levels (<16,000 sites/cell) were associated with both induction failure and more frequent relapse (p <0.01) [Cancer Research, Vol. 42, p. 4801 (1982)]. When patients with ‘high-risk’ features (leukocyte count >100 × 10³/mm³, positive erythrocyte rosette test, central nervous system involvement, and mediastinal mass) were excluded, lower receptor levels were still associated with early and more frequent relapse (p <0.02). The other 193 evaluable patients were consecutively admitted to Total Therapy Study X, in which patients with ‘standard-risk’ or ‘high-risk’ features were assigned to separate protocols — XS and XH, respectively. Induction chemotherapy in both protocols consisted of prednisone, vincristine and l-asparaginase; patients in the XH protocol received additional epipodophyllotoxin (VM-26) and cytosine arabinoside twice a week for 2 weeks preceding the conventional induction therapy. To compare the prognostic value of GR level in Study X with that of Study IX (which included both ‘high-risk’ and ‘standard-risk’ patients but did not separate them into different protocol groups), children in the XH and XS protocols were analysed together. The proportion of patients with ‘standard-risk’ features was the same in the two studies: 69% in Study IX and 73% in Study X. In Study X, which had a significantly better treatment result (p <0.001), lower receptor levels were not associated with induction failure, but were correlated with more frequent relapse (p <0.05). When patients in XH and XS protocols were analysed separately, however, receptor levels were no longer related to treatment outcome. Thus, GR level in childhood ALL has prognostic value, but it is not an independent factor and its importance is related to the efficacy of treatment.