TY - JOUR
T1 - High-risk additional chromosomal abnormalities at low blast counts herald death by CML
AU - for the SAKK and the German CML Study Group
AU - Hehlmann, Rüdiger
AU - Voskanyan, Astghik
AU - Lauseker, Michael
AU - Pfirrmann, Markus
AU - Kalmanti, Lida
AU - Rinaldetti, Sebastien
AU - Kohlbrenner, Katharina
AU - Haferlach, Claudia
AU - Schlegelberger, Brigitte
AU - Fabarius, Alice
AU - Seifarth, Wolfgang
AU - Spieß, Birgit
AU - Wuchter, Patrick
AU - Krause, Stefan
AU - Kolb, Hans Jochem
AU - Neubauer, Andreas
AU - Hossfeld, Dieter K.
AU - Nerl, Christoph
AU - Gratwohl, Alois
AU - Baerlocher, Gabriela M.
AU - Burchert, Andreas
AU - Brümmendorf, Tim H.
AU - Hasford, Jörg
AU - Hochhaus, Andreas
AU - Saußele, Susanne
AU - Baccarani, Michele
AU - von Weikersthal, L. Fischer
AU - Hahn, M.
AU - Schlimok, G.
AU - Reichert, D.
AU - Janssen, J.
AU - Martens, U.
AU - Majunke, P.
AU - Reichert, Peter
AU - Neben, K.
AU - Korsten, S.
AU - Scholz, Ch
AU - Oldenkott, B.
AU - Heßling, J.
AU - Kingreen, D.
AU - Sperling, C.
AU - Schelenz, C.
AU - Blau, I.
AU - Urmersbach, A.
AU - Ludwig, W.
AU - Le Coutre, P.
AU - Arnold, R.
AU - de Wit, M.
AU - Pezzutto, A.
AU - Schäfer, E.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085089603&partnerID=8YFLogxK
U2 - 10.1038/s41375-020-0826-9
DO - 10.1038/s41375-020-0826-9
M3 - Article
C2 - 32382082
AN - SCOPUS:85085089603
SN - 0887-6924
VL - 34
SP - 2074
EP - 2086
JO - Leukemia
JF - Leukemia
IS - 8
ER -