p53 Deletion Yields High Response Rates but Rapid Progression and Poor Overall Survival in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.
Bibliographic record
Abstract
Abstract Background: The p53 deletion has been documented to confer poor prognosis in patients with multiple myeloma (MM) treated with either conventional chemotherapy or autologous stem cell transplant (ASCT). However, it is not clear whether primary drug resistance and/or rapid relapse account for these adverse outcomes. Objective: Evaluate the impact of the p53 deletion in patients who have undergone ASCT for MM on baseline features, response to initial therapy, progression free survival and overall survival post ASCT. Method: Retrospective review of all patients undergoing ASCT for MM at our institution from January 2000 to July 2007. Results: 31 patients with the p53 deletion intended for ASCT were identified. Four patients did not undergo transplant: 2 patients had plasma cell leukemia (PCL) and died within 4 months of diagnosis, 1 patient had primary refractory disease to all therapy and died in 1 year, and 1 patient’s stem cells could not be collected. The 28 who underwent transplant had a median age of 52 (range 30–76) and 20 (78%) were male. Immunoglobulin subtype was IgG in 14 (52%), light chain in 10 (36%), IgA in 1 (4%), IgD in 1 (4%) and non secretory in 1 (4%). 23 pts (85%) had bony disease. ISS stage was as follows: 13 (52%) stage I, 6 (24%) stage II, and 6 (24%) stage III. Seven patients presented with PCL. All patients were treated with dexamethasone based induction chemotherapy (alone or VAD), with 6 patients also receiving thalidomide. Pre-transplant status after induction therapy was 0 CR, 22 PR (92%), 1 MR (4%) and 1 SD (4%). All patients were conditioned with high dose melphalan 140–200mg/m2. There was one patient who died within 100 days of transplant. Overall responses after completion of ASCT, compared with diagnosis, in evaluable pts (n=22) included 1 CR (5%), 19 PR (86%), 2 MR (9%). Median progression free survival (PFS) for this cohort was 16.9 months (95%CI 9.1–22.3) and median overall survival (OS) was 48.2 months (95%CI 11.3–67.2) post transplant. This is considerably shorter when compared to the full cohort of MM pts transplanted at our institution during the same timeframe (n= 706): median PFS 24.4 months and median OS 76.6 months post transplant. Conclusions: Patients with the p53 deletion have a high incidence of plasma cell leukemia (29%), but most respond well to induction therapy and ASCT. However, the duration of response is short (16.9 months), nearly 8 months less than our overall results with ASCT. Furthermore, median overall survival post transplant is only 4 years, over 2 years shorter than the median of 6.4 years observed in all ASCT patients. ASCT is less effective therapy in patients with this poor prognostic marker; development of novel therapeutic regimens, including targeting p53 dysregulation pathway, may be required to improve the clinical outcome in this subset of MM.
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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) | 0.001 | 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".