Retrospective Analysis of Thromboprophylaxis Use during Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

INTRODUCTION

Thrombosis is a common complication in malignancy and its occurrence in cancer patients is associated with high mortality (HR 5.8).¹ Only 14% of transplant centers report using hematopoietic stem cell transplant (HSCT)-specific thromboprophylaxis protocol because (1) consideration of thrombocytopenia as protective from venous thromboembolism (VTE), (2) concern for bleeding risk, and (3) lack of evidence of thromboprophylaxis usage in HSCT.² We hypothesize that thromboprophylaxis (VTE ppx) could prevent VTE without additional risk of bleeding in multiple myeloma (MM) patients undergoing autologous HSCT (auto HSCT).

METHODS

Study population and data collection

We conducted a retrospective cohort study of adult patients with MM undergoing auto HSCT at Cedars Sinai Medical Center between July 2016 and August 2023. The primary endpoint was the rate of thrombotic, hemorrhagic, and death events within 30 days of auto HSCT depending on receipt of VTE ppx. For VTE ppx, heparin products were used in prophylactic doses until platelet count was lower than 50,000 / mcL at the discretion of the treating physician.

Statistical analysis

The baseline characteristics of patients by VTE ppx received were compared using the chi-squared, fisher's exact test, and the Mann-Whitney U test. Univariate logistic regression was used to predict potential clinical risk factors associated with bleeding or VTE.

RESULTS

A total of 351 MM patients were included. 244 patients (69.5%) received VTE ppx during auto HSCT admission. On average, patients received 7.8 days of VTE ppx, which most commonly (89%) was low molecular weight heparin. Between the groups who received and did not receive VTE ppx, there were significant statistical differences in ethnicity, prior VTE, and Karnofsky Performance Scale (KPS). One hundred seven of 244 patients (43.9%) who received VTE ppx were non-Hispanic Caucasians while 44 of 107 patients (41.1%) who did not receive VTE ppx were Hispanic/Latino (p = 0.0006). Prior VTE event had a higher likelihood of receiving VTE ppx (87.5% vs 67.7 %, p=0.0251). Patients with KPS greater than 80 were more likely to have received VTE ppx (94.7% vs 86.0 %, p=0.0057). Other baseline characteristics were equivalent.

Twenty one of 351 patients (5.98 %) developed a VTE at a median time of 10 days (range 0 - 26 days) post-HSCT. The mean platelet count at the time of VTE was 82,000 / mcL (range 6,000 - 237,000) .

Thirty-two of 351patients (9.1 %) had prior VTE and were considered high VTE risk. Three of 28 high risk patients (10.7%) who received VTE ppx developed VTE.

Three hundred nineteen of 351 patients (90.9 %) did not have prior VTE and were considered standard VTE risk. Two hundred sixteen standard risk patients received VTE ppx while 103 patients did not. Nine of 216 (4.17%) standard risk patients who received VTE ppx developed VTE, and 9 of 103 standard risk patients who did not receive VTE ppx (8.74%) developed VTE (OR: 0.45, 95% CI: 0.17-1.18).

Thirteen of 351 patients (3.70%) had a bleed at a median time of 13 days (range 2 - 22 days) post-HSCT with 2 major and 11 minor events. The mean platelet count at bleeding was 34,000 / mcL (range 2,000 - 133,000).

Three patients (0.85 %) died within 30 days post-HSCT. All three patients had a VTE. One patient received VTE ppx and developed a bleed. Two deaths were related to VTE.

Univariate logistic analysis did not find an association between bleeding or VTE and VTE ppx receipt/agent, age, BMI, history of smoking, prior VTE, KPS, or Comorbidity Index (HCT-CI). The female gender was associated with increased risk of VTE (OR: 2.89, 95% CI: 1.14-7.35). The duration of VTE ppx use also showed an association with decreased risk of VTE (OR: 0.78, CI: 0.64-0.96).

DISCUSSION

In this single center retrospective study, MM patients with a prior VTE were more likely to receive VTE ppx during auto-HSCT. The receipt of VTE ppx did not increase bleeding rate. In standard VTE risk patients, the administration of VTE ppx showed a trend of roughly half rate of VTE, but this difference did not reach statistical significance. However, prolonged use of VTE ppx was associated with a significantly decreased risk of VTE in both high and standard VTE risk groups. Further analyses with longer duration of follow up with higher patient numbers is in process.

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