Venkateswar Rao Pydi

Abstract Background: Acute promyelocytic leukemia (APL) accounts for approximately 10% of acute myeloid leukemia(AML) cases in adults. With the advent of targeted therapy like all- trans retinoic acid (ATRA) and arsenic trioxide, survival rates have improved leading to cure in majority of patients. The present study was designed to analyze the outcomes in newly diagnosed APL. Aims and objectives: The primary objective of this study was to analyze overall survival and relapse rate in APL. Secondary objective was to study the parameters impacting outcomes in APL. Materials and methods: All newly diagnosed patients with APL between January 2005 and December 2017 were retrospectively analyzed. Diagnosis of APL was confirmed by demonstration of PML-RARA translocation by polymerase chain reaction or fluorescence in situ hydridization. Risk stratification was done using Sanz risk. Event free survival was defined as the time from diagnosis till relapse, death or lost to follow up. Overall survival was defined as time from diagnosis till death or lost to follow up. Statistical analysis was done using SPSS software, v.25. Overall survival curves were plotted using the Kaplan-Meier method. INCLUSION CRITERIA: All cases of APL diagnosed by morphology and confirmed by RT PCR (PML RARα) were included in this study. EXCLUSION CRITERIA: Age ≤ 18yrs Death within 72 hours of admission / not taken treatment Prior chemotherapy or radiotherapy for the treatment of malignancy. Results: Data of 1396 AML patients between 2005 and 2017 was collected, of which 190(13.6%) patients had APL. Of 190 patients, 111 patients who met inclusion and exclusion criteria were analyzed. The median age at presentation was 33 years (range,19-60). The male female ratio was 1.01:1. The median duration of symptoms at presentation was 15 days (range, 3-180). According to Sanz risk grouping, high, intermediate and low risk were seen in 48 (43.1%), 46 (42.4%), 17(14.5%) patients respectively. The baseline characteristics are tabulated in Table 1. Of 111 patients, 96 (86.5%) patients received induction chemotherapy with ATRA and daunorubicin and 15(13.5%) patients received ATRA and arsenic trioxide. Induction mortality was 23(20.7%). Eighty-eight (79%) patients survived induction chemotherapy, of which 87(98.8%) were in complete molecular remission (CMR) at the end of consolidation. At a median follow up of 30 months, the event free survival rate, overall survival rate and relapse rate were 72%, 74.7% and 9% respectively. The overall survival rate in low-intermediate and high-risk groups were 84.1% and 62.5% respectively. Of eight patients who relapsed, five patients received second line chemotherapy and attained second CMR (100%). On univariate analysis, the strongest predictors for OS were high risk and bcr3 variant(p=0.007, p=<0.001 respectively). On multivariate analysis, only high risk was significant for overall survival (p=0.02). Conclusion: Majority of APL patients were high risk at presentation. High risk and bcr3 variant had significant impact on survival outcome in APL. As relapse rates were low and second CMR can be achieved with salvage chemotherapy in majority of patients, improving induction outcomes will further improve survivals in APL. Disclosures No relevant conflicts of interest to declare.

Background: Acute promyelocytic leukemia (APL) results from fusion of PML RARα gene and accounts for 10% of AML. The breakpoints on chromosome 17 are consistently located in the second intron of the RAR α gene, but on chromosome 15, there are different breakpoint cluster regions, namely bcr1, bcr2, and bcr3 located in intron 6, exon 6, and intron 3, respectively. About 70% of patients with APL have bcr‐1 or long (L)‐type transcript, 20% of patients with APL have bcr‐3 or short (S)‐type transcript, and 10% of patients have bcr‐2 or variant (V)‐type transcript Aims: The primary objective of this analysis was to study patient characteristics and outcomes in relation to bcr fusion transcripts of APL Methods: Data of all patients diagnosed as APL by PCR for PML RARα with known bcr transcripts were retrospectively analysed. Deaths within 72 hours of admission were excluded from the study. Statistical analysis was done using SPSS software, version 25. Overall survival was plotted using the Kaplan‐Meier method Results: A total of 54 patients were analysed. bcr 1, bcr 3, bcr 2 and bcr 2’3 transcripts were seen in 29(53.7%), 20(37%), 3(5.6%) and 2(3.7%) respectively. Ten out of 11 paediatric patients (91%) had bcr1 transcript at presentation. The baseline characteristics and chemotherapy regimens used are tabulated in Table 1. Differentiation syndrome during induction chemotherapy was seen in 6 (21%) and 3 (15%) patients in bcr1 and bcr 3 transcripts respectively. Five patients with bcr3 transcript, 2 patients with bcr1 transcript and one patient each in bcr2 and bcr2’3 transcripts succumbed during induction therapy. Sepsis (45%), followed by DIC (45%) were the most common causes of mortality. At a median follow up of 19 months, the overall survival rate was 93.1% and 74.3 % in bcr1 and bcr3 transcript groups respectively (p = 0.09). Summary/Conclusion: Most of the paediatric patients had bcr1 transcript at presentation. High risk at presentation was significantly higher in bcr3 group. Sepsis and DIC were the most common causes of induction mortality. Patients with bcr3 transcript had nonsignificant inferior survival compared to bcr1 image