High-risk additional chromosomal abnormalities at low blast counts herald death by CML
Authors
- 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
Journal
- Leukemia
Citation
- Leukemia 34 (8): 2074-2086
Abstract
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.