Short Term Imatinib Therapy Promotes Bone Formation in Patients with Chronic Myelogenous Leukemia (CML) Independent of Cytogenetic Response.
Daniela Hoehn, LJeffrey Medeiros, Carlos Bueso-Ramos. UT M.D. Anderson Cancer Center, Houston, TX
Background: The tyrosine kinase inhibitor, imantinib, affects osteoclast morphology and is important in osteoclast (c-FMS) and osteoblast (platelet-derived growth factor receptor [PDGF-R], c-Abl) function, suggesting that therapy may alter bone homeostasis (Fitter et al, Blood 2008; 111:2538). In this study, we assessed this possibility using digital image analysis in CML patients, and correlated the results with cytogenetic response.
Design: We retrospectively reviewed 34 patients with chronic phase CML without evidence of clonal evolution who were treated with imatinib. We compared paired bone marrow biopsy specimens, at baseline and at another time point within subsequent 48 months. Results were compared with those of conventional cytogenetics analysis. Digital imaging was executed by selecting representative areas with hematopoietic bone marrow space and bony trabeculae. The areas selected were scanned at 2 x magnification with the Image Pro Plus system (Version 6.3, MediaCybernetics, Bethesda, MD, USA). Each bony trabecula and the entire hematopoietic area excluding cortical bone were circled manually to allow for calculation of total biopsy area and total trabecular area. Areas were quantified using the ImagePro Plus software area pixel count algorithm as recommended by Teman et al (Leukemia Research 2010). Trabecular bone volume (TBV) was calculated as a percentage of area by comparing the trabecular portion of the bone marrow to the non-osseous portion.
Results: The study group included 25 men and 9 women ranging in age from 30 to 75 years. 24 (71%) patients, 18 men, 6 women, showed increase in trabecular bone volume (TBV) over time on imatinib. A severe increase (defined as >50%) was identified in 4 (12%) patients, a moderate increase in TBV (10-50%) was identified in 17 (50%) patients, and a minimal increase <10 % was observed in 3 (9%) patients. Ten patients showed a decrease in TBV: severe (defined as <50%) in 2 (6%), moderate (10-20%) in 5 (15%), and mild (<10%) in 3 (9%) patients, but all patients remaining within the range of TBV appropriate for their age group. No correlation between bone homeostasis and cytogenetic response was identified. Complete cytogenetic response was observed in 33% of patients with increased in TBV, and in 6% of patients with decreased TBV.
Conclusions: Our results indicate that imatinib therapy commonly promotes bone formation in CML patients, presumably by enhancing bone metabolism through PDGF and c-FMS pathways. No correlation between TBV and complete cytogenetic response was identified.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 165, Monday Morning