Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia

Am J Hematol. 1993 Feb;42(2):147-57. doi: 10.1002/ajh.2830420202.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Antibodies, Monoclonal
  • Biopsy, Needle
  • Bone Marrow / pathology
  • Bromodeoxyuridine
  • Cell Cycle
  • Cell Differentiation
  • Cell Division
  • Cytarabine / therapeutic use
  • Daunorubicin / therapeutic use
  • Drug Therapy, Combination
  • Granulocytes / pathology
  • Humans
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / pathology*
  • Prognosis
  • Remission Induction
  • Risk Factors

Substances

  • Antibodies, Monoclonal
  • Cytarabine
  • Bromodeoxyuridine
  • Daunorubicin