Transformed Lymphoma: Incidence and Long-Term Outcome.
Bibliographic record
Abstract
Abstract Background: Development of large cell lymphoma in patients with an underlying indolent lymphoma is usually referred to as transformation and is thought to carry a poor prognosis. Its true incidence remains unknown with reported frequencies ranging between 20–70%. Objective: To determine the annual risk of transformation in a population-based group of patients diagnosed with indolent NHL in the province of British Columbia(BC) and to evaluate their outcome after transformation. Patients and Methods: The BC Cancer Agency lymphoma database was used to identify all patients diagnosed with follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL) or small lymphocytic lymphoma (SLL) between 1986 and 2001. Exclusion criteria: diagnosis outside BC; marginal zone or MALT histology; HIV positivity; age <15 or ≥61 y; incomplete staging at diagnosis or refusal of initial recommended treatment. The definition of transformation was based on either histological confirmation (HIST) or clinical features (CLIN), which included rapid discordant nodal or extranodal growth; sudden rise in LDH to > twice previous baseline; involvement of unusual extranodal sites other than bone marrow, spleen or peripheral blood; or new hypercalcemia. The extent of transformation (limited vs advanced) and treatment were also noted. Results: 406 records have been reviewed to date with a median follow-up for living patients of 84 months (range, 1–220). Initial characteristics: median age 49 y (range, 21–60); M:F ratio 1:1; histology, FL 345 (85%), SLL 32 (8%), LPL 29 (7%). 80 patients developed transformation, 58 (73%) based on HIST and 22 (27%) based on CLIN. The likelihood of developing transformation was approximately equal for each of the three histologic subtypes: FL 20%, SLL 15%, and LPL 10%. The majority of transformations were considered advanced, 58 (73%) vs 22 (27%) limited. Most patients, 66 (83%), were treated with CHOP-like chemotherapy at transformation and, of those, 14 patients also received radiation. The 5 y, 10 y and 15 y risks of transformation were 14%, 21% and 39%, respectively, with a continuous annual incidence of transformation of 2%. The 5 y, 10 y and 15 y overall survivals for the 326 patients whose lymphoma never transformed were 92%, 84% and 72% compared to 69%, 50%, and 26% for the 80 patients whose lymphoma did transform (p<0.0001). The post-transformation 5 y overall survival (post-T 5 y OS) of all 80 patients with transformed disease was 39% and the 5 y progression free survival (post-T 5 y PFS), 33%. Patients had a better outcome after limited than advanced transformation (post-T 5 y PFS (55% vs 22%, p = 0.02) and post-T 5 y OS (63% vs 30%, p=0.007)). Patients with transformation based on CLIN vs HIST criteria did not differ in their outcome (post-T 5 y PFS 39% vs 29%, p=NS, and 5 y OS 39% vs 38%, p=NS). Conclusion: The annual risk of transformation of indolent NHL lymphoma is 2% per year continuously for at least 15 y after initial diagnosis. Patients with limited extent of transformation have a much better post-transformation survival (63% vs 30%). A clinical diagnosis of transformation is just as accurate for predicting subsequent natural history as histologic proof. The development of transformation has a significant negative impact on the survival of patients with indolent lymphoma (10 y OS reduced from 84% to 50%).
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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 | 0.002 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".