Persistence of peripheral blood and bone marrow blasts during remission induction in adult acute lymphoblastic leukemia confers a poor prognosis depending on treatment intensity

Abstract

Our objectives were to evaluate the prognostic implications of persistence of peripheral blood blasts on day 7 (D7PBb) and of bone marrow blasts >5% on day 14 (D14Mb) after initiation of induction chemotherapy in adults with acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. Records of 365 consecutive newly diagnosed adult ALL patients treated with: (a) vincristine-, doxorubicin-, and dexamethasone-based chemotherapy (VAD, n = 219; 1984-1992); or (b) fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate/high-dose cytarabine (HCVAD, n = 146; 1993-1996), were analyzed. The complete remission (CR) rates were 73% with VAD and 91% with HCVAD (P<0.0001). Three-year event-free survival (EFS) rates were 23 and 40%, respectively (P = 0.00003). The impact of D7PBb and D14BMb on outcome varied with the induction regimen. Patients treated with VAD who had D7PBb had similar EFS rates compared with patients without D7PBb (P = 0.12), but EFS was inferior if they had persistent D14BMb compared with those patients without D14BMb (P = 0.00006). In HCVAD-treated patients, EFS was significantly worse in patients with persistent D7PBb (P = 0.003) but not in patients with D14BMb (P = 0.19). By multivariate analysis, D14BMb was an independent adverse feature for patients treated with VAD, whereas D7PBb was an independent adverse feature for EFS in HCVAD-treated patients. Early clearance of leukemia cells from blood and bone marrow is associated with improved outcome in adult ALL, but the prognostic significance of D7PBb and D14BMb clearance varies with treatment efficacy.