Two Cycles of Consolidation Chemotherapy Are Associated with Similar Clinical Outcomes to Three Cycles in AML Patients with Favorable Risk Cytogenetics
Bibliographic record
Abstract
Abstract Background: Patients with core-binding factor acute myeloid leukemia (CBF-AML) have favourable outcomes when treated with standard anthracycline based induction and repeated cycles of cytarabine based consolidation. CBF-AML exhibit high rates of remission, overall survival, and relapse-free survival even without allogenic stem cell transplant (alloSCT). The exact number of consolidation cycles necessary for optimal outcomes, however is unknown. While early studies suggested that 3 or 4 cycles of high dose cytarabine (HiDAC) are associated with better outcomes relative to 1 cycle (Byrd, 1999 & Byrd, 2004), the effects of 2 cycles, has not been studied in this patient group. In this study, we evaluated the impact of 2 cycles of consolidative chemotherapy on the clinical outcomes of patients with CBF-AML. Methods: Prior to 2012 patients with CBF-AML treated in Edmonton, Canada, were intended to receive 2 cycles of HiDAC after a complete remission (CR) following a single induction cycle ± intensification treatment (given if having >5% blasts on a day+14 marrow). Following a change in institutional policy, patients treated after 2012 were intended to receive 3 cycles of consolidation treatment. c-kit testing was not available prior to 2009 but thereafter all patients with c-kit mutations were offered alloSCT in first CR. In contrast, patients treated in Vancouver, Canada underwent similar induction but were intended to receive three consolidative cycles throughout the entire study period. Pooled data was retrospectively analyzed for all patients with CBF-AML treated in these two Canadian centres between 2003-2017 using an intention to treat approach. Results: Overall, 108 patients were identified with a median age of 48 (range 17-75). Sixty-four patients (59%) were male. Seventy-four patients (68.5%) were intended for 3 cycles of consolidation therapy and 34 patients (31.5%) for 2 cycles. There were no differences in baseline characteristics of the analyzed patients (Table 1). There was also no significant difference in the number of patients who received intensification chemotherapy due to day +14 residual disease, the number of induction deaths, or CR rate at end of induction. Six patients intended to receive 2 cycles of consolidation were transplanted in CR1 compared with 5 who were intended to receive 3 cycles (p=0.09). Rates of hospitalization, median length of hospital stay, bacteremic events, intensive care requirements, and deaths during consolidation therapy did not differ significantly between the two groups. Median follow-up time from CR was significantly longer in the 2 consolidation cycle group relative to the 3 consolidation cycle group (85 months vs. 30 months, p There was no significant difference in overall survival (p=0.96; Figure 1, 5-year OS 73% for the 2 cycle consolidation group v 71% for the 3 cycle consolidation group), relapse-free survival when censored for transplant (p=0.61; Figure 2, 5-year RFS 63% for the 2 cycle consolidation group v 57% for the 3 cycle consolidation group, or event-free survival (p=0.88; 5-year EFS 54% for the 2 cycle consolidation group v 52% for the 3 cycle consolidation group) within the two groups. Multivariate analysis revealed that patients age, cytogenetics [t(8;21), inv(16)/t(16;16)], or transplantation in CR1 did not influence rates of overall survival or relapse-free survival between the two cohorts. Conclusions: These data suggest that the use of 2 chemotherapy consolidation cycles compared with 3 does not diminish relapse-free survival or overall survival in patients with CBF-AML. Reduction in chemotherapy may provide both economic and quality of life benefits for patients. Larger prospective studies are necessary to confirm these findings. Download : Download high-res image (115KB) Download : Download full-size image Disclosures Hogge: Novartis, Roche, and Sanofi: Consultancy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".