P1339: CLINICAL OUTCOMES OF PATIENTS WITH EBV+ PTLD FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION WHO FAIL RITUXIMAB: A MULTINATIONAL, RETROSPECTIVE CHART REVIEW STUDY
Bibliographic record
Abstract
Background: Post-transplant lymphoproliferative disease (PTLD) occurs following allogeneic hematopoietic stem cell transplantation (HCT) as a consequence of immunosuppression. In most cases following HCT, PTLD is associated with Epstein-Barr Virus (EBV) infection of B cells, either due to reactivation, or from primary EBV infection (Styczynski J, Haematol. 2016; Allen UD, Am J Transplant, 2019; Nijand M, Transplant Direct, 2016). Clinical practice treatment guidelines recommend rituximab as preemptive therapy for EBV reactivation (based on EBV virus load) and for treatment of EBV-driven (EBV+) PTLD following HCT. However, EBV+ PTLD patients (pts) who fail rituximab have very poor outcomes with limited treatment options. Published evidence on the clinical outcomes of these pts who fail rituximab is also limited. Aims: To describe the outcomes for pts diagnosed with EBV+ PTLD following HCT who fail rituximab in a multinational real-world setting. Methods: We conducted a large multinational, multicenter retrospective chart review study of EBV+ PTLD pts following HCT or solid organ transplantation who received rituximab or rituximab plus chemotherapy (CT) between January 2000-December 2018 and were refractory (failed to achieve complete response [CR] or partial response [PR]) or relapsed at any point after such therapy. Data was collected from 29 centers across North America (United States and Canada) and the European Union. This analysis includes pts with EBV+ PTLD following HCT who were refractory or relapsed after rituximab ± CT as first line of therapy. The Kaplan-Meier (KM) method was used to estimate the overall survival (OS). Rituximab failure date was defined as the earliest date when pts became refractory or relapsed following rituximab ± CT. Results:: A total of 81 pts with EBV+ PTLD following HCT who failed rituximab ± CT were included in the analysis. Median age at PTLD diagnosis was 49 years (interquartile range [IQR]: 33‒57) and median time to PTLD onset from transplant was 3 months (IQR: 1.9‒4.2). Median follow-up time was 1.7 months (IQR: 0.6‒3.4) from the date of PTLD diagnosis. Of all the PTLDs, 52 (64.2%) were monomorphic, 18 (22.2%) polymorphic, 2 (2.5%) early lesions, and 9 (11.1%) were unknown. The most common PTLD subtype was diffuse large B-cell lymphoma (DLBCL) (46, 56.8%). Sixty-eight (84%) pts received rituximab monotherapy and 13 (16%) pts received rituximab plus CT as first line of therapy. Seven out of 13 pts who received rituximab plus CT had received preemptive rituximab treatment for EBV viremia prior to PTLD treatment. Median OS was 0.7 months (95% CI: 0.3‒1; IQR: 0.1‒2.7) for 81 pts from rituximab failure date (Figure 1). Median OS from PTLD diagnosis was 1.7 months (95% CI: 1.1‒2.3; IQR: 0.6‒3.4). Seventy-four (91.4%) out of the 81 pts ultimately died. Causes of death comprised 50 (67.6%) related to PTLD and therapy, 10 (13.5%) graft-versus-host disease (GvHD), 5 (6.8%) from sepsis/infection, 3 (4.1%) due to primary disease leading to HCT, 2 (2.7%) organ failure, 1 (1.4%) graft failure, 1 (1.4%) from hepatic failure, and 2 (2.7%) unknown. Image:Summary/Conclusion: The prognosis of EBV+ PTLD pts following HCT who fail rituximab ± CT remains very poor with an estimated median OS of less than 1 month, highlighting the significant unmet need in this population.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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 teacher head, 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".