Late onset Pneumocystis pneumonia in patients receiving rituximab for humoral renal transplant rejection

Abstract

Rituximab has been used increasingly in the treatment of antibody-mediated rejection (AbMR) in solid organ transplantation despite the absence of clinical trials demonstrating efficacy. A contributor to the growing use of rituximab is an apparent lack of morbidity; and there are no reports of specific opportunistic infections associated with its use in renal transplant recipients. Two cases of Pneumocystis pneumonia (PCP) occurring nearly 3 years after administration of rituximab for refractory AbMR are reported herein. These cases emphasize the need for ongoing vigilant observation in patients who have received rituximab, and highlight the importance of clinical trials to establish the role of rituximab in prevention and treatment of AbMR.

Pneumocystis Pneumonia in Patients Treated With Rituximab

“…An additional report described PcP after rituximab therapy in solid transplant recipients receiving this agent for the treatment of humoral allograft rejection. 8 We identifi ed 30 patients with PcP after receiving rituximab, the largest cohort of such patients. The current study holds several important advantages over prior studies.…”

“…2 In addition, recent stud ies have suggested that the novel anti-B-lymphocyte agent rituximab may be associated with the development of PcP. [3][4][5][6][7][8][9][10][11] Rituximab is a monoclonal antibody that binds to the CD20 antigen on B lymphocytes. It has been used for both hematologic malignancies such as chronic lymphocytic leukemia and for non-Hodgkin's lymphoma.…”

“…[3][4][5][6][7][8][9][10]12 The possible mechanisms by which rituximab may be a risk factor for PcP are unclear, but the depletion of B lymphocytes may adversely alter the ability of T lymphocytes to clear Pneumocystis . 2 In addition, rituximab can also cause prolonged hypogammaglobulinemia and failure of naive B lymphocytes to differentiate into plasma cells.…”

Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones’s Locker?

“…However 2 cases of late onset PCP have also been described in where B cells counts at the time of PCP diagnosis were still low -respectively 0.01 and 0.05 x10^9/L -nearly 3 years after the administration of a single dose of RTX (500 mg) for humoral rejection [28].…”

Antibody immunosuppressive therapy in solid organ transplant

“…Although the rate of infection was similarly high in both groups (45.5% rituximab-treated vs. 53.9% controls), the mortality rate was significantly higher in the rituximab group (9.1% vs. 1.6%). 27 Other reports have documented cases of late-onset Pneumocystis jiroveci pneumonia, 28 cryptogenic organizing pneumonia 29 and JC virus associated PML 30 in patients treated with rituximab in post-transplant period. These potential complications show that the particular indications for rituximab usage must be further elucidated through larger-scale randomized trials that compare rituximab with conventional therapies.…”