TY  - JOUR
A1  - Hanfstein, Benjamin
A1  - Lauseker, Michael
A1  - Hehlmann, Rüdiger
A1  - Saussele, Susanne
A1  - Erben, Philipp
A1  - Dietz, Christian
A1  - Fabarius, Alice
A1  - Proetel, Ulrike
A1  - Schnittger, Susanne
A1  - Haferlach, Claudia
A1  - Krause, Stefan W.
A1  - Schubert, Jörg
A1  - Einsele, Hermann
A1  - Hänel, Mathias
A1  - Dengler, Jolanta
A1  - Falge, Christiane
A1  - Kanz, Lothar
A1  - Neubauer, Andreas
A1  - Kneba, Michael
A1  - Stengelmann, Frank
A1  - Pfreundschuh, Michael
A1  - Waller, Cornelius F.
A1  - Spiekerman, Karsten
A1  - Baerlocher, Gabriela M.
A1  - Pfirrmann, Markus
A1  - Hasford, Joerg
A1  - Hofmann, Wolf-Karsten
A1  - Hochhaus, Andreas
A1  - Müller, Martin C.
T1  - Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib
JF  - Haematologica
N2  - 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 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/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)
KW  - chronic myelogenous leukemia
KW  - polymerase-chain-reaktion
KW  - hybrid messenger RNA
KW  - chronic phase
KW  - cytogenetic response
KW  - no correlation
KW  - ABL gene
KW  - transcripts
KW  - breakpoint
KW  - survival
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115476
SN  - 1592-8721
VL  - 99
IS  - 9
ER  - 
TY  - JOUR
T1  - Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment
JF  - Leukemia
N2  - Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N = 166 patients) and best available drug treatment (group B; N = 261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high( P < 0.001) and non-high-risk disease (P = 0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P = 0.005) and free of drug treatment (56% vs 6%; P < 0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
KW  - chronic myelogenous leukemia
KW  - hematopoietic SCT
KW  - interferon-alpha
KW  - molecular response in cml
KW  - Imatinib
KW  - european leukemia net
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190738
VL  - 30
IS  - 3
SP  - 562
EP  - 569
ER  -