PARP inhibitors and the rising incidence of secondary myelodysplastic syndrome and acute myeloid leukemia: A comprehensive meta-analysis
Bibliographic record
Abstract
Abstract Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have transformed the management of BRCA-mutated ovarian and breast cancers. However, post-marketing surveillance has raised concerns about therapy-related myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after prolonged PARPi exposure. We conducted a pooled meta-analysis to quantify the incidence of MDS/AML associated with PARPi use and to explore associated demographic and clinical features. Methods: We performed a systematic review and meta-analysis of 17 studies, including 13 real-world observational datasets and 4 published meta-analyses. Studies were included if they reported the total number of patients treated with PARPi and the incidence or number of MDS/AML cases. Extracted variables included sample size, median age, gender distribution, mortality, and latency. A pooled incidence rate with 95% confidence intervals (CI) was calculated using a random-effects model. Results: The combined cohort included 106,793 patients treated with PARPi, including olaparib, niraparib, rucaparib, and talazoparib. A total of 1,579 cases of MDS or AML were reported. The median age across studies was 62 years, and the female-to-male ratio was approximately 53:1, reflecting the predominance of PARPi use in gynecologic malignancies. Most studies originated from high-income countries, including the United States, Japan, and Canada. The mean mortality rate among patients developing MDS/AML was 38.3%. The pooled hazard ratio (HR) for death associated with therapy-related MDS/AML following PARPi exposure was 3.37, indicating a significant increase in mortality risk. Incidence of MDS/AML varied across studies from 0.3% to 3.5%. The pooled incidence was 1.48% (95% CI, 1.41%–1.55%). Among studies reporting latency, the median time from PARPi initiation to MDS/AML diagnosis was 19.5 months. Conclusions: This meta-analysis highlights that while MDS and AML are uncommon complications of PARP inhibitor therapy, their occurrence is clinically meaningful, with an overall incidence of approximately 1.5%. The risk notably increases with extended treatment duration and is associated with substantial mortality. These results underscore the importance of vigilant hematologic monitoring in patients receiving long-term PARP inhibitors and emphasize the need for prospective studies to discover predictive biomarkers and enhance personalized risk stratification.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.010 | 0.019 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.046 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".