Dasatinib Affects Bone Homeostasis, Independent of Molecular Response, in Patients with Chronic Myelogenous Leukemia (CML)
Daniela Hoehn, Naveen Pemmaraju, Jorge E Cortes, Xuemei Wang, Rashmi Kanagal-Shamanna, Sara E Dellasala, Aziz Nazha, Hagop M Kantarjian, L Jeffrey Medeiros, Carlos E Bueso-Ramos. UT MD Anderson Cancer Center, Houston, TX
Background: Imatinib, a 1st generation tyrosine kinase inhibitor (TKI), can promote bone formation in CML patients independent of cytogenetic response. Dasatinib, a 2nd generation TKI, also may have a direct effect on bone metabolism by interfering with the c-FMS, C-src and [PDGF-R] pathways as suggested by in vitro data. In this study we assess total bone volume (TBV) data in bone marrow biopsies of dasatinib treated CML patients.
Design: We reviewed 23 chronic phase CML patients without evidence of clonal evolution; treated with dasatinib from 2006-2011. We compared paired bone marrow biopsy specimens, at diagnosis and 12-51 months after commencing dasatinib therapy. Whole slide digital imaging (Philips) was performed on all bone marrow biopsy slides. Each biopsy compartment was quantified using an area pixel count algorithm. TBV was calculated as percentage area. Morphometric results were correlated with results of conventional cytogenetics and molecular analysis obtained every 3 months. In addition, TBV results in this study were compared with an age-/gender-matched control group, as well as another group of 34 CML patients treated with imatinib.
Results: Average TBV at time of CML diagnosis in the dasatinib versus the control group was 18.7% and 18%. With a median follow up of 24 months (range 12-51), there was a significant overall increase of TBV (5.2%, p=0.22). 17 of 23 (74%) CML patients on dasatinib showed increased TBV. Five patients showed decreased TBV but remained within the range appropriate for their age group. All dasatinib treated patients showed hematological response at cytogenetic and molecular level. There was no significant correlation between degree of TBV change and decline in BCR-ABL1 transcripts. The overall change of TBV in the dasatinib study group exceeded the TBV change observed in the imatinib study group (3.2%, p=0.02.
Conclusions: Our results indicate that dasatinib therapy commonly promotes bone formation in CML patients, and at an increased rate compared with imatinib therapy. There was no correlation between TBV change and either cytogenetic or molecular response.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 218, Wednesday Morning