title: Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia.
abstract: Bromodeoxyuridine (BrdU) was administered to 86 newly diagnosed patients with standard risk acute myeloid leukemia (AML) prior to starting induction therapy and the labeling index (LI), durations of S-phase (Ts), and the cell cycle (Tc) of myeloblasts were determined. Induction therapy with cytosine arabinoside and daunomycin was subsequently started. Bone marrow biopsies were obtained on days 6 and 17 and weekly thereafter, and were treated with a monoclonal anti-BrdU antibody to determine the fate of cells labeled on day 0 by BrdU. BrdU labeled granulocytes indicating the presence of in vivo differentiation (Diff+) were identified in 48 patients ranging from 1+ (1-10 labeled cells) to 4+ (greater than 31 labeled granulocytes). When compared to 38 differentiation negative (Diff-) patients, Diff+ group had longer Ts (14.5 hr vs. 10.95 hr, P = 0.015) and Tc (59.7 hr vs. 41.7 hr, P = 0.017). Remission duration was significantly longer (no median) for 3-4+ Diff+ as compared to Diff- (median = 220 days) patients (Wilcoxon P = 0.04). We conclude that the detection of in vivo differentiation in AML patients indicates a favorable long-term prognosis either due to the presence of a substantial amount of normal residual hematopoiesis prior to starting induction therapy or due to the ability of leukemic cells to undergo differentiation.
authors.affiliation: Roswell Park Memorial Institute, Buffalo, New York.
authors.forename: A
authors.initials: A
authors.lastname: Raza
authors.forename: H
authors.initials: H
authors.lastname: Preisler
authors.forename: B
authors.initials: B
authors.lastname: Lampkin
authors.forename: J
authors.initials: J
authors.lastname: Lykins
authors.forename: C
authors.initials: C
authors.lastname: Kukla
authors.forename: P
authors.initials: P
authors.lastname: Gartside
authors.forename: Y
authors.initials: Y
authors.lastname: Sheikh
authors.forename: N
authors.initials: N
authors.lastname: Yousuf
authors.forename: M
authors.initials: M
authors.lastname: White
authors.forename: M
authors.initials: M
authors.lastname: Barcos
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000473:pathology; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors
chemical_list: D000911:Antibodies, Monoclonal; D003561:Cytarabine; D001973:Bromodeoxyuridine; D003630:Daunorubicin