The Presence of HLA DR15 Antigen in Patients with Severe Aplastic Anemia Does Not Impact Engraftment and Survival After HLA-Identical Sibling Transplantation.
Bibliographic record
Abstract
Abstract Abstract 2280 Poster Board II-257 The HLA Class II antigen DR15 (common alleles 1501, 1502) is of interest in the pathobiology of T-lymphocyte mediated marrow failure (myelodysplastic syndrome (MDS), severe aplastic anemia (SAA) and paroxysmal nocturnal hemoglobinuria (PNH). Available data suggest that the presence of DR15 in patients with MDS is associated with an increased response rate to immunosuppressive therapy (IST) with ATG. While DR15 is overrepresented in patients with SAA and PNH, its presence has not been clearly shown to correlate with outcome after hematopoietic stem cell transplant in these diseases. We studied 1422 patients with SAA (30% were DR15+) who received HLA-identical sibling bone marrow (85%) or peripheral blood progenitor cells (15%) and were transplanted in 1990 – 2006 to determine whether the presence of HLA DR15 affected hematopoietic recovery, graft-versus-host disease or overall survival. The study was confined to matched sibling transplants to eliminate HLA-disparity as a driving force for any observed differences. High resolution HLA typing to discriminate between DR15 and DR16, the serological splits of DR2 was available for all subjects. Most patients (80%) had idiopathic SAA and 50% of patients were Caucasian. Patient, disease and transplant characteristics of patients with and without DR15 were similar. Proportions of patients who had received prior IST were similar among those with and without DR15. In multivariate analysis, after adjustment for significant factors, neutrophil recovery at day 28 (odds ratio [OR] 1.02, p=0.905), platelet recovery at day 100 (OR 0.95, p=0.776), secondary graft failure at 2 years (OR 0.66, p=0.123), acute (hazard ratio [HR] 0.88, p=0.345) and chronic (HR 1.09, p=0.519) graft-versus-host disease and overall mortality (HR 1.22, p=0.102) risks were similar in patients with and without DR15. Factors associated with higher mortality after transplantation included aracteristics as reported previously, including age older than 40 years (HR 2.74, p<0.001), poor performance score at transplantation (HR 1.72, p<0.001), non-Caucasians (HR 1.40, p=0.005), transplantation of peripheral blood progenitor cells (HR 1.43, p=0.019), transplantations before 2001 (HR 1.45, p=0.006) and conditioning regimens with cyclophosphamide alone (HR 1.44, p=0.022), cyclophosphamide with busulfan (HR 1.71, p=0.001) and fludarabine with other agents (HR 2.19, p<0.001). Agents used with fludarabine were: cyclophosphamide (n=54), busulfan (n=32) and monoclonocal antibody or irradiation (n=14). The 5-year probabilities of overall survival (after adjusting for the above factors that had an adverse effect on survival) were 79% in patients who were DR15 negative compared to 75% in those who were DR15+. Based on the sample size and a type I error rate of 5%, the probability of detecting a 5% difference in overall survival between the groups is 70% and a 10% difference, 98%. In conclusion, the presence of DR15 did not impact clinical outcomes after HLA-identical sibling transplantation for severe aplastic anemia. Disclosures: No relevant conflicts of interest to declare.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".