Microgranular Variant (M3V) of Acute Promyelocytic Leukemia (APL) Does Not Have a Worse Prognosis than Classical APL in the Atra Era: A Report of 153 Patients Treated on Intergroup 0129 and Pethema LPA96 and LPA99.
Bibliographic record
Abstract
Abstract The microgranular variant (M3V) accounts for 15–20% of patients (pts) with acute promyelocytic leukemia (APL). Historically, it has been associated with a higher white blood cell count (WBC) at diagnosis and an inferior outcome compared to classical morphology. Pts with APL treated with ATRA plus chemotherapy strategies have a 3–5 year DFS of 70–80%. The prognosis of pts with M3V treated with ATRA-containing chemotherapy strategies has not been adequately studied. This analysis included 153 patients with M3V entered on the North American Intergroup protocol 0129 (INT0129), a randomized phase III study of either ATRA (INT, ATRA)or daunorubicin/cytarabine for induction (INT, DA) and ATRA maintenance or observation after intensive consolidation or PETHEMA protocols LPA96 and LPA99 in which all pts received ATRA plus idarubicin for induction, intensive consolidation and ATRA plus low-dose chemotherapy for maintenance (PETHEMA, ATRA). The median age was 39 years (range 3–79), the median WBC was 14.5 K/μL (range 0.4–550), and the median platelet count was 25 K/μL (range 1.8 – 207.0). The median follow-up time for pts on INT0129 is 9.7 years, and for pts on PETHEMA LPA96 and LPA99 is 3.2 years. The 3-year disease-free (DFS) and overall survival (OS) analyses are shown in the table below. N Median (in mo) (95% CI) DFS p-value N Median (in mo) (95% CI) OS p-value *comparison between ATRA (INT+PETHEMA) and DA; **comparison among WBC groups. NE: not estimable or not reached in this analysis INT+PETHEMA, ATRA 106 NE 77% <0.0001* 128 NE 75% <0.0001* INT, ATRA 19 NE 63% 24 NE 71% PETHEMA, ATRA 87 NE 81% 104 NE 76% INT, DA 20 8.3(6.7, 12.6) 15% 25 19.4(10.4, 41.8) 32% INT+PETHEMA, ATRA 0<WBC<10K 47 NE 89% 0.01** 52 NE 90% 0.07** 10K≤WBC<50K 37 NE 78% 48 NE 69% WBC≥50K 22 NE 54% 28 NE 58% INT, DA 0<WBC<10K 8 8.4(3.0, 24.6) 13% 0.94** 10 19.5(8.6, 41.8) 30% 0.32** 10K≤WBC<50K 6 9.2(5.2, 12.6) 17% 8 56.6(10.3, NE) 50% WBC≥50K 6 7.9(7.4, 15.9) 17% 7 13.6(6.8, 22.2) 14% In a Cox regression model, when age, gender, WBC, platelet, Hgb, ATRA treatment (ATRA vs DA), and source of pts (INT vs. PETHEMA) are included, only ATRA induction treatment (HR=0.16, p-value=0.0005) appears to be a significant prognostic factor for DFS, and age, WBC, and ATRA induction treatment (HR=0.38, p-value=0.03) for OS. These data suggest that the outcome for pts with APL M3V is excellent, influenced by the WBC at diagnosis and is not different than that of pts with classical morphology when treated with ATRA-containing strategies.
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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) | 0.000 | 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".