High-risk additional chromosomal abnormalities at low blast counts herald death by CML


  • R. Hehlmann
  • A. Voskanyan
  • M. Lauseker
  • M. Pfirrmann
  • L. Kalmanti
  • S. Rinaldetti
  • K. Kohlbrenner
  • C. Haferlach
  • B. Schlegelberger
  • A. Fabarius
  • W. Seifarth
  • B. Spieß
  • P. Wuchter
  • S. Krause
  • H.J. Kolb
  • A. Neubauer
  • D.K. Hossfeld
  • C. Nerl
  • A. Gratwohl
  • G.M. Baerlocher
  • A. Burchert
  • T.H. Brümmendorf
  • J. Hasford
  • A. Hochhaus
  • S. Saußele
  • M. Baccarani


  • Leukemia


  • Leukemia 34 (8): 2074-2086


  • Blast crisis is one of the remaining challenges in chronic myeloid leukemia (CML). Whether additional chromosomal abnormalities (ACAs) enable an earlier recognition of imminent blastic proliferation and a timelier change of treatment is unknown. One thousand five hundred and ten imatinib-treated patients with Philadelphia-chromosome-positive (Ph+) CML randomized in CML-study IV were analyzed for ACA/Ph+ and blast increase. By impact on survival, ACAs were grouped into high risk (+8, +Ph, i(17q), +17, +19, +21, 3q26.2, 11q23, -7/7q abnormalities; complex) and low risk (all other). The presence of high- and low-risk ACAs was linked to six cohorts with different blast levels (1%, 5%, 10%, 15%, 20%, and 30%) in a Cox model. One hundred and twenty-three patients displayed ACA/Ph+ (8.1%), 91 were high risk. At low blast levels (1-15%), high-risk ACA showed an increased hazard to die compared to no ACA (ratios: 3.65 in blood; 6.12 in marrow) in contrast to low-risk ACA. No effect was observed at blast levels of 20-30%. Sixty-three patients with high-risk ACA (69%) died (n = 37) or were alive after progression or progression-related transplantation (n = 26). High-risk ACA at low blast counts identify end-phase CML earlier than current diagnostic systems. Mortality was lower with earlier treatment. Cytogenetic monitoring is indicated when signs of progression surface or response to therapy is unsatisfactory.