Abstract
Venous thromboembolism (VTE) is a serious complication commonly experienced in cancer patients. Incidence of VTE typically brings poor prognosis as it represents the second most common cause of mortality in cancer patients just after the malignancy itself. Studies suggest that multiple myeloma (MM) is among the malignancies with further enhanced risk of VTE, especially in patients undergoing autologous hematopoietic cell transplantation (AHCT). However, risk factors and preventative approaches remain poorly explored. Here, we explore the incidence of VTE in MM patients undergoing AHCT, while also highlighting risk factors and preventions that may aid in preventing VTE in patients who are at higher risk.
Venous thromboembolism (VTE) represents the second most likely cause of mortality in cancer patients.1,2 Multiple myeloma (MM) patients are at a ninefold risk of developing VTE. 3 The increased risk is thought to be possibly related to the marked elevation in cytokines, including IL-1β and TNF-α, which bind to their receptors on platelets and in turn promote their activation and subsequent thrombosis.4,5 Those undergoing autologous hematopoietic cell transplant (AHCT) are at further enhanced risk.6-9 Here, we explored the dynamics of VTE in their peri-AHCT setting, defined as extending from hematopoietic progenitor cell (HPC) mobilization up to 30 days post-AHCT. Chi-square and t-tests were performed for univariate analysis of categorical and continuous variables, respectively. This was followed by multivariate analysis to account for confounding variables.
A total of 493 patients were included, and symptomatic VTE was recorded in 23 events involving 17 patients (3.5%). Of the VTE events, 11 (47.83%) occurred between mobilization and time of hospitalization for AHCT, 3 (13.04%) during hospitalization, and 9 (39.13%) post-discharge. Most VTE events were non-catheter related (95.65%). Lower extremity deep venous thromboses (DVT) were seen in 12 events (52.2%), pulmonary embolisms in 4 events (17.4%), upper extremity DVT in 3 events (13%), internal jugular thromboses in 3 events (13%), and superficial vein thrombosis in 1 event (4.4%). Seven patients (41%) had history of previous VTE, 15 patients (88.2%) were previously on immunomodulatory drugs (IMiD), and 13 patients (76.5%) were either on aspirin only (4 patients, 23.5%) or anticoagulant therapy only (6 patients, 35.3%) or a combination of both (3 patients, 17.7%). A total of 155 patients (29.4%) had a smoking history. Only one patient had a history of inherited hyper-coagulopathy (Factor V Leiden heterozygous).
Patients who developed VTE had higher female preponderance (64.7 vs 40.1%, P = 0.04) were more likely to have Hematopoietic Cell Transplantation-specific-Comorbidity Index (HCT-CI) ≥ 1 (100 vs 79.4%, P = 0.03), neutropenia (<1500/uL (12.5 vs 3%, P = 0.045), and history of prior VTE (41.2 vs 11.6%, P < 0.0001; Table 1), including history of prior VTE in 2 years pre-mobilization (35.29 vs 7.35%, P = 0.0014). Our multivariate analysis confirmed the higher risk of VTE in the peri-transplant period in females (HR 3.02; 95% CI 1.03–10.07) and history of prior VTE (HR 5.32; 95% CI 1.68–15.86).
Baseline Characteristics of the VTE and Non-VTE Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplant.
*P < 0.05. Abbreviations: VTE, venous thromboembolism; AHCT, autologous hematopoietic cell transplant; IgG, immunoglobulin G; MM, multiple myeloma; ISS, international scoring system; PR, partial response; VGPR, very good partial response; CR, complete response; ImiD, immunomodularity drug; HCT-CI, hematopoietic cell transplantation-comorbidity index.
Less patients with VTE were on aspirin at VTE diagnosis relative to patients without VTE at any of the AHCT phases (41.2 vs 65.6%, P = 0.039), while a similar proportion of them was on prophylactic anticoagulation (11.8 vs 5.9%, P = 0.28). Notably, a higher percentage were on therapeutic anticoagulation (41.2 vs 11.6%, P = 0.0025), likely reflecting the inherent effect of prior VTE on the incidence of recurrent VTE in this patient population during the studied time period. Among patients with no prior VTE, patients who did not experience a VTE event were more likely to be on either aspirin or prophylactic anticoagulation (82.6 vs 50%, P = 0.02). Of note, no difference was seen in the incidence of VTE with aspirin versus prophylactic anticoagulation in patients without a history of prior VTE (1.86 vs 0%, P = 0.9).
In summary, the risk of VTE is low at around 3.5% in the immediate peri-transplant period. The use of VTE prophylaxis among MM patients undergoing AHCT significantly lowers its incidence. Antiplatelets are as effective as prophylactic anticoagulation in preventing VTE in those with no prior history of VTE, and may provide an alternative option, especially in the setting of thrombocytopenia. Having a history of prior VTE remains the biggest factor of subsequent VTE in the peri-transplant phase despite treatment with therapeutic anticoagulation.
Footnotes
Data Availability
Data would be made available upon request by the editor.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics Approval
This study was approved by the internal Institutional Review Board.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
