TY  - JOUR
A1  - Proetel, Ulrike
A1  - Pletsch, Nadine
A1  - Lauseker, Michael
A1  - Müller, Martin C.
A1  - Hanfstein, Benjamin
A1  - Krause, Stefan W.
A1  - Kalmanti, Lida
A1  - Schreiber, Annette
A1  - Heim, Dominik
A1  - Baerlocher, Gabriela M.
A1  - Hofmann, Wolf-Karsten
A1  - Lange, Elisabeth
A1  - Einsele, Hermann
A1  - Wernli, Martin
A1  - Kremers, Stephan
A1  - Schlag, Rudolf
A1  - Müller, Lothar
A1  - Hänel, Mathias
A1  - Link, Hartmut
A1  - Hertenstein, Bernd
A1  - Pfirrmann, Markus
A1  - Hochhaus, Andreas
A1  - Hasford, Joerg
A1  - Hehlmann, Rüdiger
A1  - Saußele, Susanne
T1  - Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV
JF  - Annals of Hematology
N2  - The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
KW  - chronic myeloid leukemia
KW  - older patients
KW  - different imatinib dose regimens
KW  - early applied higher imatinib dosages
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121574
SN  - 0939-5555
VL  - 93
IS  - 7
ER  - 
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  -