PB1937 CHROMOSOMAL ABERRATIONS IN CHRONIC MYELOID LEUKEMIA AND THEIR IMPACT ON RESPONSE TO CONVENTIONAL TYROSINE KINASE INHIBITORS AND RISK OF BLASTIC TRANSFORMATION.

Abstract

Background:Chronic Myeloid Leukemia(CML) is a common hematological malignancy with tyrosine kinase inhibitors(TKI) forming the main stay of treatment.Aims:The purpose of this project was to study the clinical presentation of patients with CML harboring additional chromosomal abnormalities at diagnosis and disease outcomes.Methods:This is a retrospective chart review of all patients who were diagnosed with CML in chronic phase (CP) with additional chromosomal abnormalities (ACAs) over a period of 5 years from 2010 to 2015 at our institution.Results:Response to initial TKI A total of 283 patients were diagnosed with CML from January 2010 to January 2015. Thirty one patients were found to have ACAs at the time of diagnosis in addition to BCR‐ABL fusion gene.23 patients (74.2%) were males whereas 8(25.8%) were females. 13(41.9%) were in the age group of 31 to 50 years. 30 patients were started on Imatinib and one on Nilotinib. 16 patients (51.6%) achieved complete hematological response within 3 months. However a complete molecular and cytogenetic response was never achieved in 17 (54.8%) and 18 (58.1%) patients respectively.Cytogenetics Analysis and ACAs Conventional cytogenetic analysis revealed that 11 (35.5%) of patients had variant Philadelphia chromosome followed by 7 patients (22.6%) with trisomy 8. 5 patients (16.1%) had multiple chromosomal abnormalities including trisomy 8, deletion 1 and isochrome 17q.Risk of blastic transformation Eight patients (25.8%) transformed to acute myeloid leukemia(AML) whereas 3 (9.7%) patients had a transformation to acute lymphoblastic leukemia(ALL).Therapy and response in transformed patients Out of the 11 patients who transformed to AML and ALL, 6 patients underwent induction chemotherapy while 5 were not considered fit for it on account of poor performance score and lack of resources. Out of these 6 patients, none responded to induction chemo.Summary/Conclusion:In summary, this study aimed to look at the clinical presentation of patients with CML harboring additional chromosomal abnormalities at diagnosis, cytogenetic analysis, risk of blastic transformation and response to treatment in transformed patients. Despite an early hematological response, more than half of the patients failed to achieve complete molecular and cytogenetic response which clearly shows suboptimal response to the tyrosine kinase inhibitors in this particular set of CML patients. There was transformation to acute leukemia in 35.5% of patients. We were able to give induction chemotherapy to only 6 out of 11 patients and none of them responded to it. This study showed that presence of ACA at the time of diagnosis is a high risk feature for patients with CML and confers poor prognosis when treated with conventional TKI. Further studies are required in our population regarding alternative therapy for such patient population.