The Incidence of Venous Thromboembolism (VTE) in 892 Allogeneic Hematopoietic Cell Transplant (allo-HCT) Recipients ( A single institution study comparison of VTE incidence with sirolimus versus non-sirolimus-based GVHD prophylaxis)

Background:VTE is a potentially life threatening condition that requires early recognition and treatment. An increased incidence of VTE with sirolimus-based immunosuppressive regimen has been reported in solid organ transplant. Limited data exist on VTE incidence in allo–HCT with sirolimus-based GVHD prophylaxis.

Materials and Methods:  We analyzed 892 consecutive allo-HCT recipients between 1/1/2008 and 12/31/2013 at Moffitt Cancer Center. Baseline characteristics and VTE events were collected. The association between VTE and baseline characteristics including sirolimus and non-sirolimus GVHD regimen was assessed using the Cox proportional hazard model. The significance level was set at ≤ 0.05. All analyses were performed using Stata statistical analysis software version 13.

Results: The median age was 53 (19-76) years old. The most common myeloablative preparative regimens consisted of fludarabine and pharmacokinetically-targeted IV busulfan (FLU-BU with AUC of 3500 - 9000) in 94% of cases. The most common reduced intensity regimen used was fludarabine and melphalan (52%). Baseline characteristics are described in the table. The overall incidence of VTE was 6.7% for the entire cohort: 7.2% and 6.4% in the sirolimus and non-sirolimus groups, respectively, with odds ratio (OR) = 1.14 (95% CI 0. 67-1.95; p=0.63). Of the VTE incidence, catheter related VTE were 37% and 36% for the sirolimus and non-sirolimus groups, respectively. Median onset of VTE was 155 and 233 days with sirolimus and non-sirolimus, respectively. In multivariate analysis the risk of VTE increased with every 10-year increment of recipient age with OR = 1.29 (95% CI 1.03-1.61; p=0.026).

Conclusion:  The use of sirolimus-based regimen did not increase the incidence of VTE in allo-HCT recipient. Every 10-year increment in age was associated with 29 % increased risk of VTE.

Table. Patient, disease, and treatment related characteristics (N=892)

Variables	Results
Recipient median age (range), years	53 (19-76)
Recipient gender (%)	F= 43% M= 57%
Donor/recipient gender (%) F/M F/F M/M,F	27% 21% 52%
Donor source (%) MRD MUD MMD Cord blood	32% 43% 16% 7%
Cell source (%) PBSC BM Cord blood	92% 1% 7%
Diagnoses (%) AML/MDS Lymphomas ALL Others	47% 13% 14% 26%
Preparative regimen (%) FLU-BU* Others	72% 30%
GVHD prophylaxis (%) Non-sirolimus (MTX/MMF based) Sirolimus-based	62% 37%
Recipient/Donor CMV serologic status +/+ +/- -/+,-	22% 29% 49%

 

*includes pharmacokinetically-targeted IV busulfan with a median daily AUC ranging from 3500 to 9000 μmoles min/L