PS1044 THE PROGNOSTIC SIGNIFICANCE OF BCR‐1 AND BCR‐3 ISOFORM OF PML‐RARA AND FLT3‐ITD IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA
Bibliographic record
Abstract
Background: Acute promyelocytic leukemia (APL) has a characteristic peculiar morphologic, genetic features and more favorable outcome. 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. 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. 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. 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. image
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".