Impact of Thrombotic Events Occurring during Active Treatment of Leukemia on the Overall Survival and Event-Free Survival: A Systematic Review
Bibliographic record
Abstract
Introduction Venous thromboembolism (TE) is a well-recognized complication of cancer, both in pediatric and adult populations. Adult oncology studies indicate a possible negative association between venous TE and survival. Despite pediatric patients with acute lymphoblastic leukemia (ALL) being at higher risk for TE, the association between TE and survival has been insufficiently examined. This systematic review investigates the following question: Within pediatric (0-18 years old) and adolescents and young adult (18-39 years old) (AYA) patients with ALL, what is the impact of the development of TE on the overall survival (OS) and event-free survival (EFS) compared to those without TE? Methods A comprehensive search strategy was developed in Embase, MEDLINE, and CINAHL databases (accessed June 14, 2021). Original research papers in English reporting the OS and EFS of pediatric and AYA population with ALL and TE were included. To ensure reliability, two reviewers independently screened titles, abstracts, and full-text articles for inclusion. Conflicts were resolved by a third member and through further discussion with the team. This systematic review's protocol was approved by PROSPERO. Results Our electronic search identified 5361 unique citations (Figure 1). Following the exclusion of duplicates, 4605 titles and abstracts were screened. Of these, 4326 studies did not meet the inclusion criteria and 279 full-text studies were screened further. Of these, 17 studies met the inclusion criteria and were included in this systematic review. Demographic data of the included studies can be found in Table 1. From the seventeen included studies, 10 were retrospective chart review, one was a retrospective case-control study, four were prospective studies, and two were population based retrospective cohort studies. The majority of the included studies (n=15, 88%) had TE as a primary or secondary aim. All included studies had patient populations with ALL, and two of these studies had additional patients with acute myeloid leukemia. From the seventeen included studies, a total of 9227 patients were included in this systematic review, of which 504 patients developed TE, corresponding to a prevalence of 5.46%. Overall, thirteen of the included studies provided mortality as a categorical variable; however, eleven of these thirteen studies only provided this data for those with TE. Of the eleven studies, which included 504 patients with TE, 33 patients died, corresponding to a mortality rate of 6.55%. Four of the included studies provided EFS and OS as the primary outcome, however, only three of these studies provided these outcomes for both patients with and without thromboembolism. Crude analysis of these three studies, which included 4423 patients, revealed an OS of 83.97% and EFS of 81.73% for those with TE, compared to OS of 95.8% and EFS of 94.83% for those without TE. Conclusion While a meta-analysis of the included studies in this systematic review could not able to be performed given the heterogeneity of the studies, we did identify a lower survival rate in the TE population, compared to the population without TE, as evidenced by the relatively lower OS in the TE population, as well as the corresponding mortality rate of 6.55%. Many of the included studies had varying definitions for survival, and inconsistently reported the survival data for both populations with and without TE. Indeed, only four of the included studies provided EFS and OS as outcomes and the remaining thirteen studies provided categorical data, including survival rates, and mortality rates. We recommend that future studies should include consistent definitions of survival, and such data should be provided for both populations of patients with and without TE. Additionally, we intended to conduct a subgroup analysis on AYA population, as this often is an under-studied population. Unfortunately, only one of the seventeen included studies provided data on AYA population. We thus recommend future studies investigating outcomes of TE in ALL patients, specifically include AYA populations. Discussion This review's strengths include its comprehensive search strategy created in consultation with a health sciences librarian, and a protocol that was established a priori. One limitation is our inclusion of solely English studies, thus limiting the data retrieved from non-English speaking countries. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
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 | 0.009 | 0.045 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.009 |
| Bibliometrics | 0.010 | 0.013 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".