PB1927 BCR‐ABL1/ABL REDUCTION RATIO SUPERIORITY OVER EMR AND HALVING TIME AS A PREDICTOR FOR OUTCOME IN EGYPTIAN CHRONIC PHASE CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH TYROSINE KINASE INHIBITORS
Authors: M. Elbogdady, S. Shamaa, E. Azmy, T. Abozeid, M. AbdElmoety, Z. Emara
Journal: HemaSphere (2019)

Background: Treating CML has taken tremendous leaps in the last two decades with the introduction of TKIs, This evolution has been accompanied by evolution in the diagnosis and monitoring of CML with the introduction of terms of cytogenetic and molecular response. EMR is known for its strong predictive value in CML patients But the kinetics of BCR‐ABL1 transcript decrease might be more precise in predicting Patients outcome. Aims: The aim of this study is to compare EMR, halving time and reduction ration of BCR‐ABL1 transcript level, using ABL as a housekeeping gene, at 3 months from TKI therapy as predictors for outcome regarding event free survival (EFS) and major molecular remission (MMR) at 12 months. Methods: In this study, we evaluated 60 newly diagnosed chronic phase CML patients Egyptian patients who were treated in the oncology center Mansoura University with follow up ranging from 1 8 to 51 months, QPCR was assessed on end of months 1,2,3,6,12,18,24, 36 and 48 for patients achieving these milestones, HT and RR were assessed with their specific equations at 3 months, ROC curve &amp; Youden Index were used to identify cutoff values &amp; Kaplan Mayer test was used for survival assessment. Events defined as failure according to ELN guidelines, loss of attained response, progression to accelerated or blastic phase, death. Results: all outcomes were significantly superior for the 51 patients with EMR, so did for the 30 patients with halving time ≤ 19 days and the 42 patient with reduction ratio ≥ 0.11. EFS was correlated with EMR, HT and reduction ratio in a positive manner with EFS was met in 51 patients who achieved EMR (37 were censored) Vs event in the form of treatment failure in 4 who didn’t achieve EMR (5 were censored) which was not significant (P = 0.208). EFS was met in 30 patients who achieved HT ≤ 19 days (24 were censored) Vs event in the form of treatment failure in 30 patients who had HT &gt; 19 days (18 were censored) which was not significant (P = 0.088). EFS was met in 42 patients who achieved reduction ratio &gt; 0.11 (34 were censored) Vs event in the form of treatment failure in 18 patients who had reduction ratio &lt; 0.11 (8 were censored) which was significant (P = 0.002).Achievement of MMR at 12 months was associated with attaining EMR at 3 months, MMR was positive in 64.7% versus 33.3% in patients who had EMR versus those who were EMR negative while No MMR was found in 35.3% Vs 66.7% for the same groups respectively, however this was not statistically significant P = 0.131. Achievement of MMR at 12 months was also associated with 3 months halving time ≤ 19 days, MMR was positive in 73.3% Vs 46.7% in patients whose halving time was ≤ 19 days versus those who were &gt; 19 while No MMR was found in 26.7% Vs 53.3% for the same groups respectively, this was statistically significant P = 0.035. Achievement of MMR at 12 months was also associated with 3 months reduction ratio ≥ 0.11, MMR was positive in 73.8% Vs 26.2% in patients whose reduction ratio ≥ 0.11versus those who were &lt; 0.11 while No MMR was found in 27.8% Vs 27.2% for the same groups respectively, this was statistically significant P = 0.0001. Summary/Conclusion: In conclusion, our study demonstrated that at 3 months’ time point BCR‐ABL1/ABL RR ≥ 0.11 from baseline is superior to HT ≤ 19 days and EMR in predicting EFS and MMR at 12 months with sustained response up to 48 months.