Patient Characteristics and Early Death Predictors in Acute Promyelocytic Leukaemia Patients; Experience from United Arab Emirates (UAE)
Authors: Alzaabi Mariam Rashed , Hassan Inaam bashir , Tallman Martin S , Alam Arif , Al qawasmeh Khalid , Kristensen Jorgen 
Published: October 2019

Abstract
Background: Acute promyelocytic leukemia (APL) is a highly curable subtype of acute myeloid leukemia (AML). APL has unique morphological, cytogenetic and molecular characteristics. Although extensive data regarding APL are available from developed countries only few studies have been published from developing countries. They describe higher early death rates with lower complete remission rate compared to patients from developed countries. In a retrospective analysis, we evaluated the characteristics features at presentation and predictor of early death in 67 patients with APL diagnosed between 2000 and 2015 at two centers in UAE. To our knowledge there are no published data on APL early death rates from the United Arab Emirates (UAE)
Patients and Methods: All patients age >15 years with a newly diagnosis of APL between January 2000 and January 2013 at Tawam hospital and Sheikh Khalifa Medical City (SKMC) were included. The initial diagnosis was typically based on clinical, morphological & phenotypic (negative expression of CD34 and HLA-DR but positive expression of CD2 and CD9) suspicion of APL. Subsequently the diagnosis was confirmed with genetic study for detection of t(15:17). Oral ATRA was immediately started at the standard dose 45 mg/m2 per day in addition to supportive care to correct the coagulopathy (fresh-frozen plasma, cryoprecipitate to maintain fibrinogen at >1.5 g/l, and platelets was maintained at >30x109/l). Early death was defined as death within 30 days of a patient being diagnosed with APL. Data were analyzed using SPSS version 21 (IBM SPSS Inc., Chicago, IL).
Results: The median age was 33 years (15 - 57) with only 18 (26.9%) of the patients were older than 40 years. Patients were more likely to be male (42, 62.7%), present with bleeding (53, 80.3%) at the time of diagnosis, have a WBC count greater than 10x109/L in 59.9% while in 40% of the patients it was < 5 x109/L. They tend to have platelet count < 30x109/L in 76.1%, high INR in 66.7% and < 1.5g/L fibrinogen in two third of them. 69.2% of them had bcr1 and 10 of the patients (14.9%) had t(15:17) with additional chromosomal abnormalities include monosomy7 (2 patients), trisomy 8 (1 patients), del 9 (1 patients), ring chromosome 6 (2 patients), der 21 (1 patients) and complex karyotype (3 patients).
Early death rate was 11.9%(8/67 patients). In a univariate analysis of the prognostic factors, early-deaths occurred significantly more frequent in patients who were >40 years of age (27.8% versus 6.1%; p= 0.015), those who presented with fever (21.2% versus 2.3%; p=0.030), WBC count >20 x 109/L (26.1% versus 4.5%; p=0.010), high INR (17.7% versus 0.0%; p=0.047), high APTT (40% versus 7.4%; p=0.021) at the time of diagnosis. Although fibrinogen level <1.5g/L was not identified as a significant predictor (21.1% versus 5.1%; p=0.062) of early death, a level of <1.0 g/L emerge as a significance (30.0% versus 4.3%; p=0.010) predictor in addition to the breakpoints other than bcr1 (25.0% versus 3.7%; p=0.043). Time to start of ATRA (>24h versus within 24h) therapy failed to show statistical significance (13.3% versus 12.5%; p=0.9). Patients with WBC count <5.0x109/L have tendency to less frequent early death (3.7% versus 17.5%; p=0.08). None of the patients with additional chromosomal abnormalities experienced early death (0.0% versus 14.0%). However the difference was not statistically significant (p=0.26).
Conclusion: The patient characteristics of UAE APL patients at presentation are similar to other published data. Early death rate is comparable to that published from developed countries. Our data support that coagulopathy at presentation is a major contributor to early death and that treatment of APL with improvement of early death rate is feasible at centers in developing countries provided access to facilities for aggressive supportive care.

Disclosures
No relevant conflicts of interest to declare.