Elderly acute lymphoblastic leukemia (ALL) patients are often unfit for neither dose-intensive chemotherapy nor stem cell transplantation, thus their clinical outcomes have been dismal. The increased incidence of BCR-ABL translocation with increasing age also contributed to poor prognosis but, it was our conjecture that the introduction of potent tyrosine kinase inhibitors (TKI) targeting ABL, BCR-ABL translocation might not deliver negative prognostic impact in elderly ALL. Considering that many elderly Ph- ALL patients do not tolerate cytotoxic chemotherapy required for effective tumor control, we supposed that efficacy of ABL TKIs and their combination strategy with low dose cytotoxic chemotherapy would result in better survival for elderly Ph+ ALL compared to their Ph- counterparts.
This study was a multicenter longitudinal cohort study of elderly de novo ALL (≥ 60 years) recruited from 11 hospitals in Korea from January 2005 to December 2015. We considered Ph+ if it was positive in at least one of three techniques: conventional cytogenetics, fluorescence in situ hybridization, or quantitative real-time polymerase chain reaction (qRT-PCR).
Among the 96 patients enrolled, there were 50 Ph- ALL patients (52.1%) and 46 Ph+ ALL patients (47.9%). There were no differences between the 2 groups regarding age, sex distribution, performance status, and induction regimens. For treatment outcomes evaluation, the 5 Ph+ ALL patients not receiving TKI were eliminated and 41 Ph+ ALL patients treated with TKI were compared with 50 Ph- ALL patients (Table). Complete remission (CR) was attained in 27 (54.0%) of patients in the Ph- group versus 35 (85.4%) in the Ph+ group (P=0.001). The median RFS was significantly longer in the Ph+ group (3.1 months for Ph- vs. 8.9 months for Ph+, P=0.017). Induction death and induction failure occurred significantly more often in the Ph- group. The median OS was 6.3 months for Ph- group versus 10.3 months for Ph+ group (P=0.033).
In conclusion, using real world data, this study reports the possible favorable impact of Ph+ in TKI-era for elderly patients.
Citation Format: Ja Min Byun. Prognostic impact of Philadelphia chromosome in elderly acute lymphoblastic leukemia patients ineligible for hematopoietic stem cell transplantation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 765. doi:10.1158/1538-7445.AM2017-765