Outcomes of Salvage Chemotherapy and Autologous Stem Cell Transplantation for Relapsed or Refractory Primary Mediastinal Large B Cell Lymphoma (PMLCL) Are Inferior to Diffuse Large B Cell Lymphoma (DLBCL).
Bibliographic record
Abstract
Abstract INTRODUCTION: PMLCL is an aggressive subtype of non-Hodgkin’s lymphoma with a distinct clinical and gene expression profile. While the results of primary therapy for PMLCL have been shown to be superior to those of DLBCL, the outcomes of salvage chemotherapy and autologous stem cell transplantation (ASCT) for relapsed or refractory disease are not well characterized. We studied the overall response rate (ORR) of this group of patients (pts) to second-line chemotherapy and compared their progression-free (PFS) and overall survival (OS) to a group of pts with DLBCL. METHODS: We retrospectively reviewed our computerized database and charts between Jan 1st 1995 until Dec 31st 2004 and identified 37 pts with PMLCL who underwent salvage chemotherapy. 143 consecutive pts with DLBCL that received salvage chemotherapy between Jan 1st 1999 and Dec 31st 2004 were also identified to serve as a cohort for comparison. All pts had disease that did not respond to or relapsed after initial anthracycline-based chemotherapy. Responses have been retrospectively assessed using International Workshop Criteria. Pts typically received 2–3 cycles of platinum-based salvage therapy to assess chemotherapy sensitivity; responding pts proceeded to PBSC mobilization and subsequent ASCT. The conditioning regimen consisted of high-dose VP16 60 mg/kg day −4 and melphalan 160 mg/m2 day −3 with PBSC infusion day 0. Pts with bulk disease at relapse (> 5cm) received involved field radiation post-ASCT. RESULTS: The median age at the time of salvage chemotherapy was 34 (range 21–64) in the PMLCL group vs. 50 (18–64) in the DLBCL group (P < 0.0001, Wilcoxon test). Advanced stage disease at salvage was found in 46% of PMLCL pts. vs. 49% of DLBCL pts (p=0.74 chi-square test). The distribution of primary refractory (57% PMLCL, 44% DLBCL) and relapsed pts (43% PMLCL, 56% DLBCL) was similar (p=0.17). The ORR to first line salvage chemotherapy was 25% in PMLCL pts vs. 48% in DLBCL pts (p=0.01, chi-square test). 22% of PMLCL and 50% of DLBCL pts were able to proceed to ASCT after all salvage chemotherapy and PBSC mobilization (p=0.002, chi-square). At two years post diagnosis of relapsed or refractory disease, the OS of the PMLCL pts was 31% vs. 50% in DLBCL pts (p=0.03). For pts undergoing ASCT, the 2-year post-ASCT OS (67% PMLCL vs. 59% DLBCL, p=0.99) and PFS (57% PMLCL vs. 36% DLBCL, p=0.64) were similar. Multivariate analysis to determine predictors of survival after progression found that ECOG performance status (2–3 vs. 0, HR=2.9,p=0.01) and primary refractory disease (HR=2, p=0.003) were predictive of OS. Survival was not significantly different between PMLCL and DLBCL types (p=0.18). Multivariate analysis to determine predictors of ORR to salvage chemotherapy showed that ECOG (1 vs. 0, OR=2.6, 2–3 vs. 0, OR=2.6, p=0.05), primary refractory lymphoma (OR= 6.1, p<0.0001) and PMLCL type (OR =2.5, p=0.05) were predictive of lack of response to salvage chemotherapy. CONCLUSIONS: In this “intent to transplant” analysis, relapsed or refractory PMLCL had an inferior ORR and survival from time of progression when compared to DLBCL. PMLCL pts who have chemosensitive disease have an OS and PFS post-ASCT that is similar to pts with DLBCL. Strategies for PMLCL should focus on improved salvage therapies for refractory and relapsed disease.
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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 | 0.000 | 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".