Cytoreduction and prognosis in acute lymphoblastic leukemia--the importance of early marrow response: report from the Childrens Cancer Group.

Abstract

To quantify the residual marrow lymphoblast fraction that best defines patients at high risk for relapse, and the optimal time for assessment during remission induction. The residual lymphoblast percentage was evaluated on day 7 (n = 220) and day 14 (n = 205) during a four- or five-drug induction in patients with poor prognostic factors. The rate of cytoreduction was related to event-free survival (EFS) and other factors. On the New York (NY) regimen, 68%, 14%, and 18%, and on the Berlin-Frankfurt-Munster (BFM) regimen, 56%, 15%, and 29% of patients had M1 (< 5% blasts), M2 (5-25%), or M3 (> 25%) responses on day 7 (P = .075). On day 14, the corresponding values were 87%, 6%, 7% on NY and 84%, 8%, 8% on BFM. For patients who achieved remission by day 28 and a day-7 marrow rating of M1, M2, or M3, the 6-year EFS rate was 78%, 61%, and 49% (P < .001). The day-14 ratings predicted for a 72%, 32%, or 40% EFS (P < .001). Patients with 5% to 10% blasts day 7 had three times as many events as those with less than 5% and had no better EFS than those with 11% to 25% blasts. Patients with a WBC count more than 200,000/microL at diagnosis and an M1 day 7 marrow had an EFS rate of 69%, while for those with M2 or M3, the EFS rate was 41%. Day-7 marrow had greater prognostic significance than the day-14 evaluation. For slow responders on day 7, the day-14 marrow provided additional information. EFS for patients who achieved M1 by day 14 was 65%. EFS decreased to 20% for those still M2 or M3 on day 14. Day-7 and -14 evaluations had significance for patients of all ages and WBC levels. Marrow aspiration on day 7 of therapy provided more useful information than that on day 14. However, day-14 marrow provided additional information for patients with a poor day-7 response. The rate of cytoreduction is a powerful, independent prognostic factor that can identify patients with a slow early response who are at risk for a short remission duration.