Residual bone marrow leukemic progenitor cell burden after induction chemotherapy in pediatric patients with acute lymphoblastic leukemia

We used highly sensitive multiparameter flow cytometry and blast colony ass ays to quantify the leukemic progenitor cell (LPC) burden of postinduction chemotherapy bone marrows from newly diagnosed and relapsed pediatric patie nts with acute lymphoblastic leukemia (ALL), Of 890 newly diagnosed patient s, 243 (27%) had detectable LPC in the postinduction bone marrow samples wi th an average (mean +/- SE) LPC content of 22 +/- 9 LPC/10(6) mononuclear c ell (MNC; range, 0-7199/10(6) MNC; median, 0/10(6) MNC), By comparison, 24 of 50 (48%) patients with relapsed ALL had detectable LPC in their postindu ction bone marrow specimens (P = 0.003), and their average LPC content was 202 +/- 139 LPC/10(6) MNC, Fewer patients with B-lineage ALL (170 of 786; 2 2%) than patients,vith T-lineage ALL (73 of 104; 70%) harbored residual LPC in their postinduction bone marrow specimens (P < 0.0001), This correlatio n,vith immunophenotype was independent of the National Cancer Institute ris k classification, Similarly, 19 of 44 (43%) patients with relapsed B-lineag e ALL versus 5 of 6 (83%) patients with relapsed T-lineage ALL harbored res idual LPC in their postinduction bone marrow specimens (P = 0.09), Among ne wly diagnosed patients, those with high-risk ALL seemed to have larger numb ers of residual LPC in their bone marrow after induction chemotherapy than those with standard risk ALL (53 +/- 26, n = 286 versus 7 +/- 1, n = 604, P = 0.04), LPC of patients with standard risk ALL who had a slow early marro w response at day 7 seemed to be more resistant to the three-drug induction chemotherapy than patients who had a rapid early marrow response. Overall, the order of chemosensitivity of LPC was: newly diagnosed standard risk B- lineage > newly diagnosed higher risk B-lineage > newly diagnosed standard risk T-lineage > newly diagnosed higher risk T-lineage > relapsed B-lineage > relapsed T-lineage, Notably, LPC- patients whose end-of-induction remiss ion bone marrow specimens had zero LPC had an excellent early event-free su rvival outcome, Within the standard and high-risk subsets, LPC- patients ha d a 2.6-fold lower and 2.4-fold lower incidence of events, respectively, th an LPC+ patients. At 6 months, 12 months, as well as 24 months, the ranking order for better event-free survival was: standard risk, LPC- > high risk, LPC- > standard risk, LPC+ > high risk, and LPC+.