HLA-DR Protein Status Predicts Survival in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Treated with the MACOP-B Chemotherapy Regimen.
Bibliographic record
Abstract
Abstract Background: HLA-DR is one of the MHC Class II antigen presenting molecules. Loss of HLA-DR expression on DLBCL tumor cells has been associated with poor survival in patients on Southwest Oncology Group (SWOG) studies as well as the recent Leukemia and Lymphoma Molecular Profiling project (Rosenwald et al, NEJM 2002). This study was conceived to examine the effect of HLA-DR status on a completely different cohort of patients from a single institution treated uniformly with a single chemotherapy regimen, MACOP-B, in an attempt to validate HLA-DR as an important biomarker in DLBCL. Methods: HLA-DR immunostaining was performed using a tissue microarray block containing two 0.6mm cores of paraffin embedded tissues from 97 patients treated on the MACOP-B regimen (1981–86) at the BC Cancer Agency in Vancouver, Canada (Semin Hematol 1988, suppl 2: 41–6). Only cases of B cell lineage were used. We used the HLA-DR antibody Class II DR, (IgG2b) at a 1:50 dilution (Novocastra, UK) with epitope recovery, on an automated immunostainer (Ventana Benchmark System) using a biotin-avidin-diaminobenzidine-based detection system. Two pathologists (LR and DF) scored all slides for positive or negative results. Results: All patients had advanced-stage disease and were treated uniformly with the MACOP-B chemotherapy regimen. The median follow-up of living patients is 17 years. The IPI was predictive of overall survival (OS) in the study group (p = 0.023). Of the 97 B cell cases, 82 had interpretable staining. The other cases were eliminated for lack of tumor (2), necrotic tissue (1), or lack of internal positive control cells in the tissue core (12). Of the remaining 82 cases, 52 were positive for HLA-DR protein with a median OS of 16.2 years while 30 were negative with a median OS of 4.2 years, (p=0.037, figure below). A Cox multivariate model established both IPI (p = 0.031) and HLA-DR status (p = 0.04) as independent predictors of OS. Discussion: The importance of loss of antigen presenting molecules on cells of DLBCL was a key finding of the previous LLMPP work, and is now further confirmed as impacting OS in a separate set of patients treated uniformly with a different chemotherapy regimen. These findings lend credence to the hypothesis that loss of immunogenicity is of key importance in patient response to treatment and OS and suggest that specific therapies focused on this pathway may benefit patients with DLBCL regardless of their treatment regimen. Figure Figure
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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 | 0.001 |
| 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) | 0.001 | 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".