7079 Background: The treatment of (CML) has undergone major changes in the past decade with the introduction of tyrosine kinase inhibitors (TKI). However the initial enthusiasm is waning with increasing recognition of drug resistance. There is an urgent need to identify the types of receptor mutations which lead to drug resistance and their significance in salvage therapy. Methods: We identified 17 males and 8 female patients with median age 40 yrs (range 9–55 years) with CML who were on imatinib at the time of loss of hematologic response (HR), cytogenetic (CyR), or molecular response (MR) and performed imatinib-resistance mutation analysis. The sequencing was done on ABI machine by direct sequencing method. Results: This group included 22 patients with chronic phase (CP) disease, 2 patients with accelerated phase (AP), and 1 patient with extramedullary blast crisis (BC). Fourteen patients received treatment with agents other than imatinib as the first-line therapy due to either nonavailability of the drug at the time of diagnosis in India, but were started on imatinib when drug became available. The other 11 patients received imatinib as first-line therapy. The best response to imatinib included major CyR in 14 patients which included 3 patients with complete CyR and minor CyR in 6 patients. Lack of HR was noted in 2 patients in whom CyR was not evaluated. Imatinib resistance mutation analysis was prompted by no HR (n = 2); loss of HR after achieving CyR (n = 9); failure to achieve CyR milestones (n = 3); loss of CyR (n = 9); development of extramedullary BC (n = 1). The analysis revealed no mutations-11 patients, M351T-4 patients, G250E-3 patients, F317L-2 patients, M244V- 1 patient, T315I-1 patient, F382L-1 patient, results awaited in 4 patients with 2 patients showing 2 mutations. Conclusions: The majority of patients 11/25 had no detectable mutations while T315I which confers resistance to all TKIs was detected only in 1/25 patients who demonstrated loss of response in our population. The correlation of the other mutations to loss of response and the response to second line TKI needs to be studied in further detail. In addition analysis of mutation patterns at baseline may help in stratifying patients for treatment. No significant financial relationships to disclose.
20512 Background: Considering the high cost of intensive high-dose methotrexate based chemotherapy, a non-methotrexate based chemotherapy regimen was evaluated in newly diagnosed osteosarcoma patients Methods: A total of 54 patients of newly diagnosed osteosarcoma (2000 to 2005) were included in the study. Chemotherapy protocol included 3 drugs viz. Doxorubicin (20 mg/m2 on Day1 to Day3), Cisplatin (100 mg/m2 on Day 1) and Ifosfamide (2000 mg/m2 on Day1 to Day 5) in combination as A1 cycle - Ifosfamide + Doxorubicin, B1 cycle - Doxorubicin + Cisplatin, C1 cycle - Cisplatin + Ifosfamide. The sequence was repeated as A2, B2 and C2 (total 6 cycles). Surgical excision of primary tumor was done after 3 cycles of chemotherapy Results: The median age at diagnosis was 15.5 years with a slight male preponderance (n=38, 70.4 %). Axial skeleton (maxillary) was affected only in one patient. Lower end of femur was the most common appendicular skeletal site for the primary tumor (n=27, 50 %). Forty two out of 54 (77.8 %) patients had nonmetastatic disease at diagnosis. Lung was the most common site of distant metastasis at diagnosis (11 out of 12 patients). Fifty patients received all 6 chemotherapy cycles as planned. Limb salvage with reconstruction surgery was performed in 35 (64.8 %) patients. Complete (100%) tumor necrosis was seen in 18 (33.3 %) patients. The median duration of follow-up was 16 months. The actuarial disease free and overall survival at 3 years would be 41.4 % and 43.6 % respectively. The incidence of febrile neutropenia was 11.85 % and of grade III/IV thrombocytopenia was 10 % of all chemotherapy cycles. Easily controllable emesis was the commnoest non-hematological toxicity, experienced by 31.5 % of patients. Two patients died due to post chemotherapy neutropenic sepsis. With univariate analysis, complete histological response (100 % tumor necrosis) alone could be identified as independent favorable prognostic factor (3 year OS of 73.6 %, P=0.003). The overall survival outcome was not statistically different in subgroups of sex, age group and pathological tumor size. Conclusions: Non-methotrexate based triple drug combination chemotherapy is an effective treatment option for patients with newly diagnosed osteosarcoma in developing countries like India. No significant financial relationships to disclose.
Second malignancies or co-existing malignancies like ovarian, endometrial, lung carcinomas, soft tissue sarcomas have been reported to be associated with breast carcinoma. The commonest cause of bone pain in a patient of breast cancer is metastasis to bone. We present a rare case of multiple myeloma mimicking bony metastasis in a patient of breast carcinoma.
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