Cancer Res Treat.  2016 Jan;48(1):312-321. 10.4143/crt.2014.266.

Cross-sectional Study of Patients with Diffuse Large B-Cell Lymphoma: Assessing the Effect of Host Status, Tumor Burden, and Inflammatory Activity on Venous Thromboembolism

• Lim SH
• Woo SY
• Kim S
• Ko YH
• Kim WS
• Kim SJ

• KMID: 2152290
• DOI: http://doi.org/10.4143/crt.2014.266

Abstract

PURPOSE
The risk factors for venous thromboembolism (VTE) in diffuse large B-cell lymphoma (DLBCL) are not clear although thrombosis can be associated with host status, tumor burden, and inflammatory activity. We assessed the effect of those factors on VTE in a cross-sectional study of patients enrolled in a prospective cohort study.
MATERIALS AND METHODS
We analyzed the occurrence of VTE in 322 patients with newly diagnosed DLBCL who received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) between 2008 and 2011. Serum levels of inflammatory cytokines were measured from serum samples archived at diagnosis.
RESULTS
With a median follow-up duration of 41.9 months, VTE was documented in 34 patients (10.6%). A comparison of baseline characteristics indicated the group with VTE had higher percentage of old age, stage III/IV and extranodal involvements than the group without VTE (p < 0.05). Thus, the International Prognostic Index was significantly associated with VTE, but the Khorana score was not. A univariate competing risk factor analysis for VTE revealed that increased levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 were also associated with VTE (p < 0.05) in addition to host and tumor burden. However, a multivariate analysis showed that two host factors including age (> or = 60 years) and poor performance were independent risk factors for VTE.
CONCLUSION
Among potential risk factors for VTE including tumor burden and inflammatory activity, age and performance status had a strong impact on the occurrence of VTE in patients with DLBCL who received R-CHOP.

Keyword

Diffuse large B-cell lymphoma; Venous thromboembolism; Risk factors; Chemotherapy

MeSH Terms

B-Lymphocytes*
Cohort Studies
Cross-Sectional Studies*
Cyclophosphamide
Cytokines
Diagnosis
Doxorubicin
Drug Therapy
Follow-Up Studies
Humans
Interleukin-10
Interleukins
Lymphoma, B-Cell*
Multivariate Analysis
Prednisone
Prospective Studies
Risk Factors
Thrombosis
Tumor Burden*
Venous Thromboembolism*
Vincristine
Cyclophosphamide
Cytokines
Doxorubicin
Interleukin-10
Interleukins
Prednisone
Vincristine

Figure

• 

  Fig. 1. Study design: cross-sectional analysis. This prospective cohort study aimed to develop a predictive model for treatment outcomes and treatment-related morbidity (such as VTE in this study) in patients with lymphoma. VTE, venous thromboembolism; DLBCL, diffuse large B-cell lymphoma; LDH, lactate dehydrogenase; IPI, International Prognostic Index; CRP, C-reactive protein.

• 

  Fig. 2. Comparison of International Prognostic Index (IPI) and Khorana score on the occurrence of venous thromboembolism (VTE). Patients with high or high-intermediate (H/HI) IPI risk (18%, 19/108) had significantly more VTE events than those with low or low-intermediate (L/LI) IPI risk (7%, 15/214; p=0.05). Khorana risk classification did not show significant association with VTE (Khorana score high [≥ 3] group [H], 24%; low/intermediate group [L/I], 10%; p=0.25).

• 

  Fig. 3. Comparison of inflammatory biomarkers in patients with and without venous thromboembolism (VTE). The mean serum levels of inflammatory biomarkers plasminogen activator inhibitor-1 (PAI) (A), regulated on activation, normal T cell expressed and secreted (RANTES) (B), interleukin (IL) 10 (C), IL-6 (D), interferon gamma-induced protein 10 (IP-10) (E), and tumor necrosis factor α (TNF-α) (F) were not significantly different between patients with and without VTE.

• 

  Fig. 4. Comparison of host factors, tumor burden and inflammatory cytokines on the occurrence of venous thromboembolism (VTE). The occurrence of VTE was associated with old age (A), advanced stage (B), presence of interleukin (IL) 6 (C), poor PS (D), extranodal involvements (E), and elevated serum interferon gamma-induced protein 10 (IP-10) level (F). ECOG PS, Eastern Cooperative Oncology Group performance status.

• 

  Fig. 5. Comparison of survival rates between patients with and without venous thromboembolism (VTE). The overall survival rate was not significantly different between patients with or without VTE.

Reference

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