Venous Thromboembolism Post-allogeneic Hematopoietic Cell Transplant: Risk Factors, Incidence, and Outcomes

Abstract

Background Venous thromboembolism (VTE) is a well-documented complication of both solid and hematologic malignancies, but there are fewer data on allogeneic hematopoietic cell transplant (HCT) recipients. Therefore, we studied the incidence, risk factors, and impact of VTE on post-HCT outcomes in a contemporary cohort.

Methods We retrospectively reviewed patients who underwent allogeneic HCT between January 2014 and August 2019 to identify patients with post-HCT VTE. Patient, disease, and transplant-related risk factors for VTE were investigated using competing risk analysis.

Results A total of 431 patients were included in this study. Median (interquartile range [IQR]) age in years was 59 (46–65) at transplant. The most common indication for transplant was acute myelogenous leukemia (49.4%). Within our cohort, 64 patients (14.8%) developed post-HCT VTE with a median (IQR) follow-up time of 24.6 (8.4–47.1) months. The cumulative incidence of VTE was 4.2% at 6 months, 9.0% at 12 months, 12.6% at 24 months, and 13.8% at 36 months. In multivariable analysis, older age (hazard ratio [HR] per 10-year increase: 1.36, 95% confidence interval [CI]: 1.09–1.70), history of VTE (HR: 1.95, 95% CI: 1.09–3.49), and grade 2–4 acute graft versus host disease (GVHD; HR: 1.75, 95% CI: 1.05–2.94) were independently associated with VTE. VTE was significantly associated with an increased risk of nonrelapse mortality (NRM; HR: 4.09, 95% CI: 2.47–6.74) and decreased overall survival (OS; HR: 2.19, 95% CI: 1.48–3.24).

Conclusion VTE is an important complication after allogeneic HCT and is significantly associated with increased NRM and decreased OS. Older patients, those with prior VTE, and patients with acute GVHD are at increased risk for development of VTE after HCT.

Keywords

venous thromboembolism - deep vein thrombosis - malignancy

• References

• 1 El Jurdi N, Elhusseini H, Beckman J. et al. High incidence of thromboembolism in patients with chronic GVHD: association with severity of GVHD and donor-recipient ABO blood group. Blood Cancer J 2021; 11 (05) 96
• 2 Kekre N, Kim HT, Ho VT. et al. Venous thromboembolism is associated with graft-versus-host disease and increased non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Haematologica 2017; 102 (07) 1185-1191
• 3 Chaturvedi S, Neff A, Nagler A, Savani U, Mohty M, Savani BN. Venous thromboembolism in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2016; 51 (04) 473-478
• 4 Gerber DE, Segal JB, Levy MY, Kane J, Jones RJ, Streiff MB. The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention. Blood 2008; 112 (03) 504-510
• 5 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111 (10) 4902-4907
• 6 Sanfilippo KM, Luo S, Wang TF. et al. Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score. Am J Hematol 2019; 94 (11) 1176-1184
• 7 Al-Ani F, Wang YP, Lazo-Langner A. Development of a clinical prediction rule for venous thromboembolism in patients with acute leukemia. Thromb Haemost 2020; 120 (02) 322-328
• 8 Kirkizlar O, Alp Kirkizlar T, Umit EG. et al. The incidence of venous thromboembolism and impact on survival in Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 2020; 20 (08) 542-547
• 9 Zahid MF, Murad MH, Litzow MR. et al. Venous thromboembolism following hematopoietic stem cell transplantation-a systematic review and meta-analysis. Ann Hematol 2016; 95 (09) 1457-1464
• 10 Labrador J, Lopez-Anglada L, Perez-Lopez E. et al. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients. Haematologica 2013; 98 (03) 437-443
• 11 O'Hara VJ, Miller T, Mehta R, Swartzendruber E, Kiel PJ. Incidence of venous thromboembolism in the setting of hematopoietic cell transplantation. Am J Ther 2014; 21 (01) 15-19
• 12 Martens KL, da Costa WL, Amos CI. et al. HIGH-2-LOW risk model to predict venous thromboembolism in allogeneic transplant patients after platelet engraftment. Blood Adv 2021; 5 (01) 167-175
• 13 Gangaraju R, Chen Y, Hageman L. et al. Late-occurring venous thromboembolism in allogeneic blood or marrow transplant survivors: a BMTSS-HiGHS2 risk model. Blood Adv 2021; 5 (20) 4102-4111
• 14 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
• 15 Li A, Martens KL, Nguyen D. et al. External validation of the HIGH-2-LOW model: A predictive score for venous thromboembolism after allogeneic transplant. Am J Hematol 2022; 97 (06) 740-748
• 16 Deng RX, Zhu XL, Zhang AB. et al. Machine learning algorithm as a prognostic tool for venous thromboembolism in allogeneic transplant patients. Transplant Cell Ther 2023; 29 (01) 57.e1-57.e10
• 17 Martens KL, Amos CI, Hernandez CR. et al. Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation. Am J Hematol 2021; 96 (09) 1137-1146