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THE PROGNOSTIC SIGNIFICANCE OF BCR-1 AND BCR-3 ISOFORM OF PML-RARA AND FLT3-ITD IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA

PS1044

Rasekh, E.1; Elsayed, G.1; Madney, Y.2; El Gammal, M.3

doi: 10.1097/01.HS9.0000562472.96992.e6
Poster Session II: Acute myeloid leukemia - Clinical
Free

1Clinical pathology

2Pediatric oncology

3Medical Oncology, NCI, Cairo University, Cairo, Egypt

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Background:

Acute promyelocytic leukemia (APL) has a characteristic peculiar morphologic, genetic features and more favorable outcome.

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Aims:

is to study the differential effect of BCR-1 and BCR-3 isoforms of PML-RARA together with FLT3-ITD mutational status on outcome of APL patients.

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Methods:

All patients referred to the outpatient medical and pediatric oncology clinic, National cancer institute (NCI), Cairo University, Egypt in the period from May 2012 to January 2018. The diagnosis of APL was based on morphologic examination of the bone marrow and peripheral blood smears and was confirmed by the detection of the PML-RARA transcript by FISH and RT-PCR.

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Results:

the study included 118 patients with newly diagnosed de novo APL (71 (60%) adults and 47 (39.8%) children). Based on the initial TLC, pediatric APL patients have higher (48.9%) risk than adults (30%) (p = 0.044). The CR rate was 91% (77/84), after excluding early induction related deaths (18) and patients who did not receive treatment at NCI (no beds available) (16). All pediatric patients (both BCR-1 and BCR-3) and all adult patients with BCR-3 achieved CR while 22/28 (78.5%) of patients with BCR-1 achieved CR (p = 0.04). Adult patients with FLT3 mutation (5/8 = 62.5%) received more high-risk regimen than patients with wild FLT3-ITD (10/38 = 26.3%)(p = 0.047). FLT3-ITD mutation was associated with more hemorrhage and DIC (p = 0.038), and lower 2-year OS (96% v 44.6%)(p = 0.001) in pediatric patients. Also DIC and Hemorrhage are associated with lower 2-year OS in pediatric patients (91.4% v 48.6%)(p < 0.001). The 1-year and 2-year OS for pediatric patients were better than adults (56.2% v 83% and 80.7 % v 49.8% respectively) with a median of 39.4 month versus 12month respectively (p = 0.005). On multivariate analysis, Age was an independent prognostic variable affecting survival, HR 2.6 (95% CI 1.3-5.3, P= 0.007)(adults had hazards ratio of death 2.6 times higher than pediatrics). DIC & FLT3-ITD were independent prognostic variables affecting survival in the pediatric APL with HR 12.3 (95% CI 1.46-104.61, P = 0.021) and 5.2 (95% CI 1.01-26.95, P = 0.048) respectively.

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Summary/Conclusion:

BCR-1 isoform of PML-RARA is associated with decreased response to ATRA-based regimens in adult APL patients. DIC & FLT3-ITD are adverse prognostic factors in pediatric APL patients. Age is an independent prognostic factor in APL patients (whole group). Despite higher high risk groups in pediatric patients, the outcome is better than adult patients.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.