Significance of Bone Abnormalities In CML Patients on Imatinib Mesylate Therapy

Abstract 4759

Both Dasatinib and Nilotinib have proven themselves as more effective but costly first line therapy in chronic myeloid leukemia (CML) than imatinib mesylate (IM). Hence, IM would continue to be used as first line therapy in developing countries because of economic reasons. Thus simple diagnostic tools are required which can triage CML patients into different risk categories. Presence of bone abnormalities (osteoblastic, osteolytic and mixed) in CML was generally associated with poor outcome in pre-imatinib era. Nuclear bone scintigraphy is a simple test that has universal availability. The significance of these abnormalities in imatinib-era has not been investigated. We proposed to evaluate the significance of bone abnormalities as seen on nuclear scintigraphy in CML at diagnosis and at follow-up. The bone scintigraphy was performed with 99m Tc methylene di phosphonate 3-hours after an intravenous injection of 740 MBq of the radiotracer. Regions of interest (ROI) were marked using standard software. A second ROI was marked on the diaphyseal region of the involved long bone. The ratio of average counts per pixel between the involved and the normal areas was calculated for each long bone. The average ratios of the right and left half of body were calculated separately. This average scintigraphic quantification ratio were compared before and after IM therapy. The standard investigations including bone marrow examination and cytogenetics studies were done at diagnosis and at follow-up. The bone scintigraphic abnormalities were correlated with cytogenetic remission after 6 months of IM therapy. The starting dose of IM in chronic phase was 400 mg/day and in advanced phase 600 mg/day. The study was approved by institute review board and was carried out according the declaration of Helsinki. Forty-three newly diagnosed CML patients gave consent for the study. The mean age of patients was 40.8+14.6 and male female ratio was 25:18. Thirty-two patients were in chronic phase and 11 were in advanced phase (accelerated or blast crisis). The prevalence of bone scintigraphy abnormalities were found in 76.7% patients (75% in chronic phase and 81% in advanced phase, p =0.06). No bone abnormalities were detected in 10 patients. At a median follow-up of 7 months (range 5–8 months of IM therapy), 16% patients achieved completed cytogenetic remission (CCR) and 80% achieved partial cytogenetic remission (pCR). The average bone quantification decreased from 3.34+1.05 to 2.07+0.44 among patients in CCR and 2.47+0.57 among patients in pCR. One CML patient showed increase in bone quantification from 3.61 at baseline to 4.14 at 6 months and on bone marrow examination, he was diagnosed in blast crisis. No relationship of bone abnormalities was found with Sokal score at baseline. Bone abnormalities as seen on nuclear scintigraphy are thus common among patients with CML. They tend to resolve on IM therapy. However, a longer follow-up of patients is required for further evaluation of this technique in CML patients and whether it can replace sophisticated prognostic molecular techniques which are inaccessible in resource-constraints settings.