Many patients with acute lymphoblastic leukemia (ALL) find success with induction therapy, an attempt to induce remission with a short, intense course of chemotherapy. But in a minority of patients induction fails, and the reasons for this aren't well understood. The authors of a recent retrospective study reviewed data from 14 cooperative groups that recruited more than 44,000 children and adolescents with newly diagnosed ALL into clinical trials between January 1985 and December 2000. A total of 1,041 patients experienced induction failure, as measured 28 to 43 days after treatment initiation. The rates of induction failure varied from 1.4% to 4.9% because of the studies' differing definitions of induction failure, as well as differences in the length and intensity of induction therapy.
Although there was great heterogeneity among patients experiencing induction failure, the authors found that this subset of patients were more likely to have certain characteristics: male sex; an age older than six years at diagnosis; a high leukocyte count; leukemia with a T-cell phenotype; central nervous system involvement; 11q23 chromosomal rearrangement; and positivity for t(9;22)(BCR-ABL1), the Philadelphia chromosome. Patients with certain other characteristics tended to have better 10-year survival rates: high-hyperdiploid ALL (a survival rate of 71%) and ETV6-RUNX1 genetic aberrations (a 73% survival rate).
Especially poor outcomes were noted in patients who had T-cell leukemia, 11q23 rearrangement, 25% or more leukemic blasts in bone marrow (M3 marrow) at the end of induction, and were 10 years old or older. Also, the 10-year survival rate was lower (26%) among patients with M3 marrow after induction therapy, compared with the rate (41%) among those with either M1 marrow (less than 5% leukemic blasts) or M2 marrow (5% to 24% leukemic blasts).
Allogeneic hematopoietic stem-cell transplantation was shown to provide benefit to patients with T-cell ALL who experienced induction failure, although it didn't improve outcomes in patients younger than six years who had precursor B-cell ALL, induction failure, and no high-risk cytogenetic abnormalities. The authors note that the latter finding is particularly significant, given that transplantation is the standard of care in these patients.