The Autoantibody Response to ALK In Pediatric Anaplastic Large Cell Lymphoma: A Children's Oncology Group Report
Bibliographic record
Abstract
Abstract Abstract 4130 Introduction: Pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas (ALCL) are characterized by the expression of aberrant ALK fusion proteins, the most common of which is nucleophosmin (NPM)/ALK. Interestingly, an autoantibody response to the ALK oncoprotein has been described. Objective: To determine the prevalence and prognostic significance of immune response to the ALK oncoprotein, we analyzed the serum autoantibody response to ALK in a large cohort of uniformly treated advanced stage ALK-positive pediatric ALCL patients enrolled into the ANHL0131 trial (a randomized phase III trial with standard APO versus consolidation with a regimen including vinblastine (J Clin Oncol 28:15s, 2010) and correlated the results with clinical features and patient outcome. Methods: A total of 129 eligible patients were enrolled in this study. Analysis was performed through May 2009 with a median follow-up of 2.9 yrs (0.13-4.7 yrs). ALK expression was determined by immunohistochemistry performed on tissue sections. Patients were stratified according to stage and the involvement of mediastinum, visceral organs, central nervous system and bone marrow. Serum samples were obtained from 64 patients at the time of diagnosis. A subset of the patients (n=43) were also evaluated at the end of induction. An indirect immunoperoxidase technique using cytocentrifuge preparations of COS cells transfected with cDNA encoding NPM/ALK were stained with the patient's serum and the highest dilution of the serum samples at which staining of the transfectants was observed was determined as the titer of the antibody. Three groups of patients were identified: antibody dilutions 0-≤1/750 (low), 1/2025-<1/60750 (intermediate), and ≥1/60750 (high). Results: Autoantibodies to ALK were detected in the serum of 64/64 (100%) patients at the time of diagnosis. Sixteen patients (25%) showed high antibody titers against ALK, 25 patients (40%) intermediate titers and 23 patients (36%) low titers. There was an inverse relationship between autoantibody titers and event-free survival which did not reach statistical significance (p=0.14) due to small number of overall rate of failure (9/64 patients). Patients with high autoantibody titers at diagnosis had a somewhat better 4-year event-free survival (100%) than those with lower antibody titers (intermediate: 82% and low: 75%). Stage 4 and mediastinal disease appeared to be associated with low autoantibody titers (p=0.05). Those 43 patients who were also evaluated at end of induction demonstrated either no change or reduction in autoantibody titers. Conclusions: These results indicate that the autoantibody response to ALK is highly prevalent in patients with ALK-positive ALCLs. They also indicate that the presence of an immune response to the tumor may be associated with clinical response. These results are similar to those reported by NHL-BFM Study (Blood 2010:115:3314-3319). The predictive/prognostic value of autoantibody titer with regard to tumor dissemination and risk of relapse remains to be determined for this treatment regimen. 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 | 0.001 | 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 | 0.001 |
| 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".