Details

Autor(en) / Beteiligte

• Hehlmann, Rüdiger
• Voskanyan, Astghik
• Lauseker, Michael
• Pfirrmann, Markus
• Kalmanti, Lida
• Rinaldetti, Sebastien
• Kohlbrenner, Katharina
• Haferlach, Claudia
• Schlegelberger, Brigitte
• Fabarius, Alice
• Seifarth, Wolfgang
• Spieß, Birgit
• Wuchter, Patrick
• Krause, Stefan
• Kolb, Hans-Jochem
• Neubauer, Andreas
• Hossfeld, Dieter K.
• Nerl, Christoph
• Gratwohl, Alois
• Baerlocher, Gabriela M.
• Burchert, Andreas
• Brümmendorf, Tim H.
• Hasford, Jörg
• Hochhaus, Andreas
• Saußele, Susanne
• Baccarani, Michele

Titel

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

Ist Teil von

• Leukemia, 2020-08, Vol.34 (8), p.2074-2086

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.