Rituximab (R)-CHOP Therapy Has Progressed Arteriosclerosis with an Elevation of Von Willebrand Factor (vWF) in Patients with Malignant Lymphoma
Authors: Shimizu Naomi , Nakamura Shouko , Kawagoe Naoyuki , Oka Rena , Watanabe Yasuhiro , Tanaka Sho , Sato Yuta , Yamaguchi Takashi , Ohira Masahiro , Saiki Atsuhito , Nakaseko Chiaki , Sakaida Emiko , Bujo Hideaki , Shirai Kohji , Tatsuno Ichiro 
Published: October 2019

Abstract
Introduction : An increased incidence of arteriosclerosis has been noted in cancer survivors. Until now, only a few reports have been reported on relationship between arteriosclerosis and chemotherapy. As a mechanism for developing arteriosclerosis by chemotherapy, reduction of nitric oxide from endothelial cells has been reported. We have reported a case who was 68-year-old female with follicular lymphoma, clinical stage IVA showing the plaque formation of carotid artery and the elevation of cardio-ankle vascular index (CAVI) after eight courses of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) without complication of diabetes mellitus and hyperlipidemia (2017, JCMR). In this study, we evaluated the incidence of developing arteriosclerosis with chemotherapy using CAVI as an arterial stiffness parameter, carotid artery ultrasonography and the value of von Willebrand factor (vWF) as an endothelial damage in patients with malignant lymphoma who were treated with R-CHOP therapy.
Materials and methods: Between March 2017 and February 2018, thirteen patients with B-cell malignant lymphoma who were treated with R-CHOP chemotherapy were enrolled after obtaining written informed consent. We evaluated the arteriosclerosis with CAVI index, carotid artery ultrasonography and the value of vWF during each chemotherapy. This study was approved by the Ethics Committee of Toho University.
Results: Twelve men and one woman were registered (the median age, 73 years old, range, 59 - 82). One patient was treated with 4 courses of R-CHOP followed by irradiation and the remaining 12 patients were treated with 6-8 courses of R-CHOP. All patients achieved complete remission. The mean value of vWF was significantly elevated from 147 ± 40.0 % to 192 ± 39.8 % after one course of R-CHOP (p = 0.001). Then, the value of vWF was elevated significantly at the each time point compared with the pretreatment value (after 3 cycles; 190 ± 53.5, p = 0.0017, 6 cycles; 198 ± 32.5, p = 0.0024) (Figure 1). The value at after the final chemotherapy (175 ± 41.3) decreased significantly comparing the value of final treatment (207 ± 38.9, p = 0.0112). Nine patients showed the progression of arteriosclerosis with new plaque formation or progression of intima-media thickness by carotid artery ultrasonography. Plaque score after completing the therapy was elevated significantly from 6.4 ± 4.33 to 6.8 ± 4.65 (p = 0.0313) as shown in Figure 2. Some patients showed the elevation of CAVI index with the progression of treatment. However, there was no significant elevation of the index during the treatment.
Conclusions: We reported that malignant lymphoma patients showed the significant elevation of vWF and new plaque formation in carotid artery during the R-CHOP therapy. vWF elevation might have progressed the arteriosclerosis in the patients with R-CHOP therapy. Further study will be required to clarify the relationship between chemotherapy and arteriosclerosis.

Disclosures
No relevant conflicts of interest to declare.