External validation of the HIGH‐2‐LOW model: A predictive score for venous thromboembolism after allogeneic transplant

Abstract

In patients undergoing hematopoietic cell transplantation (HCT), venous thromboembolism (VTE) remains a serious complication that lacks validated risk assessment models (RAMs) to guide thromboprophylaxis. To address this dilemma, we performed a temporal and external validation study of the recently derived HIGH‐2‐LOW RAM. We selected adult patients undergoing allogeneic HCT from Fred Hutchinson Cancer Research Center (FHCRC) and MD Anderson Cancer Center (MDACC). Patients who died, received anticoagulation, or did not engraft platelets by day 30 were excluded. Primary outcomes were defined as overall VTE and pulmonary embolism ± lower‐extremity deep venous thromboembolism (PE/LE‐DVT) by day 180. Covariates were weighted according to the original model, except that grade 2–4 GVHD was substituted for grade 3–4. Discrimination and calibration were assessed. A total of 765 patients from FHCRC and 954 patients from MDACC were included. Incident VTE by day 180 was 5.1% at FHCRC and 6.8% at MDACC. The HIGH‐2‐LOW score had a c‐statistic of 0.67 (0.59–0.75) for VTE and 0.75 (0.64–0.81) for PE/LE‐DVT at FHCRC and 0.62 (0.55–0.70) for VTE and 0.70 (0.56–0.83) for PE/LE‐DVT at MDACC. Twenty‐five percent and 23% of patients were classified as high risk (2+ points) in the two cohorts, respectively. High versus low‐risk was associated with odds ratio (OR) of 2.80 (1.46–5.38) for VTE and 4.21 (1.82–9.77) for PE/LE‐DVT at FHCRC and OR of 3.54 (2.12–5.91) for VTE and 6.82 (2.30–20.16) for PE‐LE‐DVT at MDACC. The HIGH‐2‐LOW RAM identified allogeneic HCT recipients at high risk for VTE in both validation cohorts. It can improve evidence‐based decision‐making for thromboprophylaxis post‐transplant.

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

“…Recent retrospective studies have led to the development of HCT-specific, risk-assessment tools, including the “HIGH-2-LOW” score 12 15 and the “BMTSS-HiGHS2” 13 score. The “HIGH-2-LOW” score was derived to predict VTE after platelet engraftment at day 30, and includes the following factors: history of catheter-related DVT, inpatient status at day 30, GVHD grade 3–4, history of PE or lower extremity DVT, lymphoma diagnosis, obesity with body mass index ≥35 kg/m 2 , and white blood cell ≥11 × 10 9 /L.…”