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Randomized Controlled Trial
. 2014 Sep;99(9):1441-7.
doi: 10.3324/haematol.2013.096537. Epub 2014 May 16.

Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib

Benjamin Hanfstein  1 , Michael Lauseker  2 , Rüdiger Hehlmann  1 , Susanne Saussele  1 , Philipp Erben  1 , Christian Dietz  1 , Alice Fabarius  1 , Ulrike Proetel  1 , Susanne Schnittger  3 , Claudia Haferlach  3 , Stefan W Krause  4 , Jörg Schubert  5 , Hermann Einsele  6 , Mathias Hänel  7 , Jolanta Dengler  8 , Christiane Falge  9 , Lothar Kanz  10 , Andreas Neubauer  11 , Michael Kneba  12 , Frank Stegelmann  13 , Michael Pfreundschuh  14 , Cornelius F Waller  15 , Karsten Spiekermann  16 , Gabriela M Baerlocher  17 , Markus Pfirrmann  2 , Joerg Hasford  2 , Wolf-Karsten Hofmann  1 , Andreas Hochhaus  18 , Martin C Müller  19 ; SAKK and the German CML Study Group
Affiliations
Randomized Controlled Trial

Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib

Benjamin Hanfstein et al. Haematologica. 2014 Sep.

Abstract

The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier:00055874).

Trial registration: ClinicalTrials.gov NCT00055874.

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Figures

Figure 1.
Figure 1.
(A) Box plots of leukocyte counts (WBC) at diagnosis. E14a2 is associated with lower WBC (65 × 109/L, median) as compared to e13a2 (88 × 109/L, P<0.001) and e13a2+e14a2 (78 × 109/L; P=0.030). (B) Box plots of platelet counts at diagnosis. E13a2 is associated with lower platelet count (296 × 109/L, median) as compared to e14a2 (430 × 109/L; P<0.001) and e13a2+e14a2 (420 × 109/L; P<0.001).
Figure 2.
Figure 2.
Cumulative incidence of major molecular remissions (MMR).
Figure 3.
Figure 3.
Cumulative incidence of 4-log molecular remissions (MR4).
Figure 4.
Figure 4.
Cumulative incidence of complete cytogenetic remissions (CCyR).
Figure 5.
Figure 5.
Probability of progression-free survival (PFS).
Figure 6.
Figure 6.
Probability of overall survival (OS).
See this image and copyright information in PMC

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