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| Item Type: | Article |
|---|---|
| Title: | High-risk additional chromosomal abnormalities at low blast counts herald death by CML |
| Creators Name: | Hehlmann, R., Voskanyan, A., Lauseker, M., Pfirrmann, M., Kalmanti, L., Rinaldetti, S., Kohlbrenner, K., Haferlach, C., Schlegelberger, B., Fabarius, A., Seifarth, W., Spieß, B., Wuchter, P., Krause, S., Kolb, H.J., Neubauer, A., Hossfeld, D.K., Nerl, C., Gratwohl, A., Baerlocher, G.M., Burchert, A., Brümmendorf, T.H., Hasford, J., Hochhaus, A., Saußele, S. and Baccarani, M. |
| 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. |
| Keywords: | Blast Crisis, Cause of Death, Chromosome Aberrations, BCR-ABL Positive Chronic Myelogenous Leukemia, Risk |
| Source: | Leukemia |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Volume: | 34 |
| Number: | 8 |
| Page Range: | 2074-2086 |
| Date: | August 2020 |
| Additional Information: | Antonio Pezzutto is a member of the SAKK and the German CML Study Group. Erratum in: Leukemia 34(10): 2823. |
| Official Publication: | https://doi.org/10.1038/s41375-020-0826-9 |
| PubMed: | View item in PubMed |
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