P362: OUTCOMES IN PATIENTS WITH RELAPSED OR REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA RECEIVING HEMATOPOIETIC CELL TRANSPLANTATION USING REAL-WORLD DATA FROM HARMONY
Bibliographic record
Abstract
Background: Hematopoietic cell transplantation (HSCT) is a standard consolidation treatment for patients (pts) with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL). However, predicting post-HSCT survival and related outcomes remains a challenge because of limited samples, outdated published evidence, and studies focussed on de novo ALL. HARMONY Alliance is a large multi-national public-private partnership aiming to gather data on hematologic cancers currently maintained in several individual databases from clinical trials and registries across Europe. The HARMONY data platform contains anonymized data of ~10,000 pts with ALL. Aims: To estimate post-HSCT outcomes, including overall survival (OS), and to identify clinical factors correlated with post-HSCT outcomes using real-world data from HARMONY. Methods: A dataframe was constructed within HARMONY to include pts with R/R ALL who had received HSCT. OS was assessed post-HSCT using Kaplan-Meier time-to-event analyses. Results: A total of 235 adult pts diagnosed with R/R ALL between 1995 and 2019 who received ≥1 allogeneic or unspecified HSCT were included in the analysis. Most pts were male (63.8 %; n=150), Philadelphia-chromosome negative (64.7%; n=152), and had B-cell ALL (71.1 %; n=167); median age at ALL diagnosis was 25.0 years (range, 7.7‒71.0) and at HSCT was 26.8 years (range, 18.5‒71.6). Within 3 years of HSCT, acute graft-versus-host disease (GvHD) was recorded and graded in 11.1 % (n=26) of pts and chronic GvHD was recorded in 4.3% (n=10) of pts. At a median follow-up of 65.7 months (range, 0.3‒169.4), median OS (95% CI) from HSCT was 9.4 months (7.5‒13.8; Fig 1A), with a 1-year OS rate of 45.3 %, and a plateau starting from year 4. Subgroup analyses indicate variation in OS by minimal residual disease (MRD) status before HSCT, age group at HSCT, and time period of HSCT. In the limited number of records where MRD-status before HSCT was available, OS appeared longer in pts with MRD-negativity (n=17) vs MRD-positivity (n=25) at the most recent MRD assessment before HSCT (1-year OS=70.1% vs 50.1%; p=0.324, not significant]; Fig 1B). OS after 1 year was higher in pts <55 years (n=215, 47.3%) vs ≥55 years (n=20, 24.0%) p=0.025; Fig 1C). One-year OS was significantly higher in pts originally diagnosed with ALL in childhood (<18 years) with relapse and consolidating HSCT as adults (n=40, 66.5%) vs pts diagnosed as adults (≥18 years; n=195, 41.0%; p=0.005). Finally, OS following HSCT improved significantly over the historical HSCT periods of 1995‒1999 (n=36), 2000‒2009 (n=101), and 2010‒2019 (n=98); 1-year OS=25.0%, 45.5%, and 52.6%, respectively; p=0.002; Fig 1D). Median relapse-free survival (RFS; 95% CI) from HSCT was 7.6 months (6.1‒9.4), with a 1-year RFS rate of 38.8 %. Summary/Conclusion: This is one of the largest real-world studies focused on adult pts with R/R ALL. While the 1-year OS rate increased to 50% in recent time-periods, post-HSCT outcomes remain unsatisfactory. Recent transplant practices have improved survival. Factors such as younger age at diagnosis and transplant, and quality of pre-HSCT response (eg, reaching MRD-negativity) appear to positively influence post-HSCT survival.Keywords: ALL, Acute lymphoblastic leukemia, relapsed/refractory, Allogeneic stem cell transplant
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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 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 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".