Rituximab-containing Chemotherapy (R-CHOP)-induced Kaposi's Sarcoma in an HIV-negative Patient with Diffuse Large B Cell Lymphoma

Abstract

Rituximab treatment may cause or exacerbate Kaposi's sarcoma (KS) in patients with human immunodeficiency virus (HIV)-associated multicentric Castleman's disease. Despite the widespread use of rituximab, rituximab-induced KS has not yet been reported in HIV-negative patients with diffuse large B cell lymphoma (DLBCL). We herein report a case of KS that developed after undergoing rituximab-containing chemotherapy in an HIV-negative patient with DLBCL. An 84-year-old man who received rituximab-containing chemotherapy for the treatment of DLBCL developed severe infection, and subsequently KS. Our observations indicate that serious infections under rituximab treatment may trigger KS. KS should therefore be considered when skin tumors appear in lymphoma patients receiving rituximab-containing chemotherapy.

Reversible rituximab-induced rectal Kaposi’s sarcoma misdiagnosed as ulcerative colitis in a patient with HIV-negative follicular lymphoma

“…The role of CD4 T-cells in the Kaposi’s sarcoma pathophysiology is suspected [ 25 ], especially in HIV-positive patients who usually present Kaposi’s sarcoma when circulating CD4+ T-cell count is under 350/mm 3 under highly active antiretroviral therapy [ 26 ]. In our case as well as in Ureshino’s case, the CD4+ T-cell count was higher than 350/mm 3 [ 5 ], suggesting that cellular immunodeficiency played only a minor role in the development of Kaposi’s sarcoma in these patients. As B-cells are the HHV8’s main human reservoir, another hypothesis may be that B-cell depletion induced by rituximab can expose endothelial cells to high HHV8 level, causing latent viral infection, and promoting Kaposi’s sarcoma development [ 23 ].…”

“…Another case was reported in an 84-year-old patient after undergoing rituximab-containing chemotherapy (R-CHOP regimen) for the treatment of a diffuse large B-cell lymphoma (DLBCL); after the seventh cycle, the patient developed a severe bacterial pneumonia and subsequent CMV viremia. The cutaneous Kaposi’s sarcoma developed after the complete resolution of pneumonia and was treated with surgical resection [ 5 ]. Our case is the first rituximab-induced Kaposi’s sarcoma that developed at the mucosa level.…”

“…These authors also postulated that the diminished B-lymphocyte count interfered with the normal immune response to HHV8, allowing for viral activation. Unfortunately, the circulating CD20+ cell count and the Ig levels were not available for our patient, but they were low in the Ureshino’s case [ 5 ]. Despite the widespread use of rituximab, there has been only one case of rituximab-related Kaposi’s sarcoma in HIV-negative patients with DLBCL [ 5 ], and it was suggested that additional factors causing systemic inflammation, such as an infection, might contribute to the development of Kaposi’s sarcoma in addition to rituximab.…”

“…Because of its immunosuppressive effects through action on CD20 and reduction of mature B-cells, rituximab therapy may exacerbate Kaposi’s sarcoma in HIV-positive patients [ 3 ]. Rituximab-related Kaposi’s sarcomas have been previously reported in two HIV-negative patients, without multicentric Castelman’s disease [ 4 , 5 ], and were treated surgically.…”

Human Herpes Virus 8 in HIV-1 infected individuals receiving cancer chemotherapy and stem cell transplantation

“…Further study of HHV8 responses to various chemotherapeutic agents in larger cohorts of HIV-infected individuals is warranted. Rituximab, a monoclonal antibody that targets CD20 expressed on B cells, is thought to reactivate HHV8 viremia and lead to the development of clinical KS in both HIV-infected and uninfected individuals [ 16 , 17 , 18 ]. Interestingly, the participant with MCD/KS had a 1.9-log 10 reduction in plasma HHV8 following rituximab monotherapy, but also recently started on suppressive antiretroviral therapy which may have led to improved anti-HHV8 immune responses.…”