Abstract
Background: Catheter-related thrombosis (CRT) occurs frequently during autologous hematopoietic cell transplantation (AHCT) and its current management is highly variable. There is limited data regarding the incidence, risk factors, management patterns and outcomes of CRT in patients with lymphoma or myeloma undergoing AHCT.
Methods: In a retrospective observational study with nested case-control risk factor analysis, we examined 789 patients with lymphoma and myeloma who underwent AHCT at University of Minnesota between 2006-2016. We identified 50 subjects with CRT from central venous catheters (CVCs). Patient and transplant characteristics and outcomes were compared in the case-control analysis with 2:1 matching by patient age and disease. All AHCT recipients underwent insertion of tunneled 14.5fr double lumen large bore tunneled catheters for hematopoietic cell apheresis. All patients underwent routine CT chest prior to AHCT and at days 28 and 100 post-transplant. The primary objective was to describe the CRT incidence, management and complications. Secondary objective was to identify CRT risk factors. Statistical comparison of categorical variables was performed by χ2 and Wilcoxon rank-sum test was used for assessment of continuous variables between cases and controls.
Results: The incidence of CRT in patients with lymphoma and myeloma undergoing AHCT over the ten-year period was 6.3% (n=50); with 32% symptomatic. Out of 50 cases, 43 occurred within 100 days of AHCT and 94% cases were associated with tunneled line; predominantly internal jugular (90%). CRT was diagnosed between 21 days prior to 26 days after CVC insertion. Five patients had pulmonary embolism detected incidentally by CT imaging; all were asymptomatic. The median time from tunneled line placement to CRT was 44 days (11-89 days) Of the 50 patients with CRT, 22% had refractory Hodgkin's lymphoma (incidence in HL 11.0%), 62% non-Hodgkin's lymphoma (incidence in NHL 10.1%) and 16% myeloma (incidence in MM 2.1%). The median age at the time of CRT was 56.6 years; 60% were male. Prior radiation to chest/neck (18%), bulky mediastinal mass (12%), splenectomy (6%), bacteremia (18%), hormonal therapy (8%), and prior VTE (16%) were common amongst CRT cases. Half of CRT cases had a Port-a-cath and 46% had more than one CVC inserted peritransplant. Vein occlusion was complete in 46% and occurred with the same frequency on left and right (44% vs 42%). At the time of CRT, median platelet count was 133 (range 31-426 x 109/L). Median time of tunneled line removal was 0 days (ie. on same day as CRT) but ranged from 21 days before CRT to 161 days after CRT.
Most (86%) CRTs were treated with low molecular weight heparin (LMWH) and 56% received subsequent warfarin. Only 2% were treated with unfractionated heparin. LMWH at dose 1 mg/kg twice daily was administered if platelet count could be maintained above 50 x 109/L and median time to platelet recovery was 15 days (range 9-36). Patients were anticoagulated for <3 months (38%), 3-6 months (24%), and >6 months (22%). One patient required lytic therapy for CRT. Only two patients (4%) received secondary prophylactic anticoagulation after AHCT. This management was safe and effective and grade 1-2 bleeding events occurred in only two patients (4%) during anticoagulation. Five patients (10%) had CRT recurrence or extension while 12% had subsequent VTE after CRT. No deaths occurred due to CRT or its treatment.
In univariate analysis, risk factors for CRT included prior VTE event (20.9% vs 7.0%, p=0.02) and higher WBC peak at mobilization (43.5 vs 40.4 x 109/L, p=0.17) and stem cell engraftment (15.2 vs 11.9 x 109/L, p=0.18). Gender, presence of Port-a-cath, comorbidity index and Karnofsky score did not increase the risk of CRT. Two-year progression-free survival of entire group was 54% (95% CI 50-57%) and was not affected by CRT (p=0.42).
Conclusions: The diagnosis of CRT complicates AHCT and appears to be more common in patients with lymphoma than myeloma. Prior VTE is the main risk factor for CRT. Anticoagulation with LMWH or warfarin appeared safe , however many patients had recurrent VTE events. Higher WBC seems to be associated with risk of thrombosis. Further study to define additional risk factors and examine the management strategies is warranted.
Bachanova: Seattle-Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Zymogen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oxis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding.
Author notes
Asterisk with author names denotes non-ASH members.
