Venous Thromboembolism Is Hematopoietic Stem Cell Transplant Patients– a Meta-Analysis and Systemic Review

Background

Venous Thromboembolism (VTE) is a common late effect after Hematopoietic Stem Cell Transplant with wide variation in reported frequency of incidence (1-20% of patients). There is lack of data with respect to risks and outcomes of VTE, unlike sinusoidal obstruction syndromes (SOS) for which adequate literature is available. Therefore, optimal approach for prevention and management of VTE in HSCT patients is unknown.  We sought to conduct a meta-analysis of VTE incidence and evaluate its risk factors in HSCT patients.

Methods

A comprehensive search of several databases from each database's earliest inception to June 2nd, 2014 in any language was conducted by an experienced medical librarian. The databases included Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid CCT and Scopus. To avoid publication bias, we also searched annual meeting abstracts from ASBMT, EBMT, ASH, SIOP, and ISTH. The electronic search generated 755 articles. Only 34 studies met the strict selection criteria. Case reports, review articles, meta-analysis, postmortem reports, and solid organ transplants were excluded. Two investigators independently analyzed the studies for final selection. Both autologous and allogeneic HSCTs were included for any indication. SOS and thrombotic microangiopathy cases were excluded from the analysis. Only Deep Venous Thrombosis and Pulmonary embolism were included in the analysis.

Results:

Among the final 34 studies with adequate data for analysis, N was 8353. 522 patients developed DVT or PE in the cohort giving an incident rate of 6.12%. Quality appraisal was performed for clinical trials using the Cochrane Risk of Bias tool, which indicated poor quality of reporting in majority of trials with possibility of introducing bias. A meta-regression model could not be constructed due to non-uniform reporting of the outcome of interest and because of significant methodologic variation between the studies. Among the patients receiving immunomodulatory (IMiD) therapy post-HSCT (n=703), 22.7% developed VTE. Chronic graft versus host disease did not affect the rates of VTE; although most of the studies in the final cohort did not report the cGVHD incidence.  VTE incidence in autologous HSCT and allogeneic HSCT was 9.43% (196/2078) and 4.61% (180/3902) respectively [data missing or not reported for rest].

Conclusions:

VTE can be life threatening late complication of HSCT with substantial number of patients developing PE or DVT post HSCT. Results of our study with a large sample size indicate a substantial risk of VTE with IMiD usage in HSCT patients. Further studies from large database would be helpful in deciphering the associations of VTE with GVHD and establishing guidelines for prophylaxis and management.