Hehlmann, RüdigerRüdigerHehlmannVoskanyan, AstghikAstghikVoskanyanLauseker, MichaelMichaelLausekerPfirrmann, MarkusMarkusPfirrmannKalmanti, LidaLidaKalmantiRinaldetti, SebastienSebastienRinaldettiKohlbrenner, KatharinaKatharinaKohlbrennerHaferlach, ClaudiaClaudiaHaferlachSchlegelberger, BrigitteBrigitteSchlegelbergerFabarius, AliceAliceFabariusSeifarth, WolfgangWolfgangSeifarthSpieß, BirgitBirgitSpießWuchter, PatrickPatrickWuchterKrause, StefanStefanKrauseKolb, Hans-JochemHans-JochemKolbNeubauer, AndreasAndreasNeubauerHossfeld, Dieter KDieter KHossfeldNerl, ChristophChristophNerlGratwohl, AloisAloisGratwohlBaerlocher, Gabriela M.Gabriela M.BaerlocherBurchert, AndreasAndreasBurchertBrümmendorf, Tim HTim HBrümmendorfHasford, JörgJörgHasfordHochhaus, AndreasAndreasHochhausSaußele, SusanneSusanneSaußeleBaccarani, MicheleMicheleBaccarani2024-12-132024-12-132020-08https://boris-portal.unibe.ch/handle/20.500.12422/193536Blast 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.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.1444783238208210.1038/s41375-020-0826-9