Pulmonary Complications in Patients Treated with Tyrosine Kinase Inhibitors, a Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Abstract Background: In patients with chronic myeloid leukemia (CML), long-term use of tyrosine kinase inhibitors (TKIs) is associated with hematological and non-hematological complications. To investigate the pulmonary complications (pulmonary edema and pulmonary arterial hypertension [PAH]) in CML patients receiving TKIs, we conducted a systematic review and meta-analysis of clinical trials and observational studies. Methods: We searched MEDLINE, EMBASE and the Cochrane library to May 2015. The studies were included if they enrolled CML patients, used at least one of imatinib, nilotinib, dasatinib, bosutinib and ponatinib, and reported pulmonary effusion or PAH as one of their outcomes. We performed a single proportion meta-analysis for the cumulative incidence of each outcome. Subgroup analysis was carried out based on type of TKI, phase of disease, dosage and line of treatment. Results: Thirty-nine studies, involving 6562 patients were included in the meta-analysis. The overall cumulative incidence of pleural effusion was 5% (95% confidence interval [CI]; 4.2-5.8, I2=95.9%). Subgroup analysis according to type of TKI revealed that dasatinib was associated with highest incidence of pleural effusion, 26.2% (95%CI; 21.4-31.1) compared to imatinib (0.5%), nilotinib (0.1%), bosutinib (2.1%) and ponatinib (0.3%), Figure 1. Subgroup analysis demonstrated that accelerated/blastic phase, non-first line treatment and higher dose of dasatinib were associated with a higher risk of pleural effusion. There were 7 cohorts reporting PAH. The overall cumulative incidence of pleural effusion was 0.2 per 100 patient year (95% CI; -0.3, I2 =0%) for all TKIs, Figure 2. Conclusions: Pleural effusion is a frequently found pulmonary complication among CML patients receiving dasatinib. However, PAH is uncommon for TKI treated patients. We recommend a low threshold for performing a chest x-ray in symptomatic patients on dasatinib. Because of the low incidence of PAH, we cannot recommend routine screening for PAH in the absence of highly suspicious symptoms. Figure 1. Cumulative incidence of pleural effusion in CML patients treated with tyrosine kinase inhibitors Figure 1. Cumulative incidence of pleural effusion in CML patients treated with tyrosine kinase inhibitors Figure 2. Cumulative incidence of pulmonary artery hypertension in CML patients treated with tyrosine kinase inhibitors Figure 2. Cumulative incidence of pulmonary artery hypertension in CML patients treated with tyrosine kinase inhibitors Disclosures No relevant conflicts of interest to declare.
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 | 0.012 | 0.029 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.017 | 0.041 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| 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".