Rituximab for Immune Thrombocytopenia: A Retrospective Analysis on the Role of Prophylaxis Against Pneumocystis Jirovecii and Herpes Zoster Virus
Authors: Raso Simona , Napolitano Mariasanta , Carlisi Melania , Mancuso Salvatrice , Santoro Marco , Siragusa Sergio 
Published: October 2019

Abstract
Introduction and objective of the study
Rituximab (RTX) is considered a valid second line treatment option for persistent or chronic Immune Thrombocytopenia (ITP). RTX is known to affect the immune system thus increasing the risk for viral and fungal infections. Although prophylactic treatment to prevent Pneumocystis jirovecii (PJ) and herpes viruses' infections is used in patients with haematological neoplasms receiving RTX, these evidence is lacking in ITP patients candidated to anti-CD20 therapy. We here reported the role of phrophylaxis in a cohort of patients treated with RTX for refractory/relapsed ITP.
Methods
Data from patients affected by ITP and treated at our Institution with RTX from January 2013 to June 2018 were retrospectively evaluated. The following data were obtained from medical records, before and after RTX treatment, up to the last available follow-up: gender, age, comorbidities, complete blood count, absolute lymphocyte count (ALC), electrophoretic proteinogram, RXT treatment schedule, prophylactic (antiviral and/or antifungal) therapy administered, clinical manifestations of PJ, Herpes Zoster Virus (HZV) and Herpes Simplex Virus (HSV) infections, confirmed diagnosis of any infection.
Results
Overall, 20 patients with ITP treated with RTX as second line therapy were analysed, Table 1 summarizes the main results of the study. All patients had previously received corticosteroids for a mean period of 9 months (range 1-36 months), 13 patients also received immunoglobulins (Ig) as first-line treatment of ITP. In one case, RTX was administered twice and one patient received also azathioprine as immunosuppressive therapy for 6 months before RTX. In 3 subjects RTX was adopted within 1 month after the diagnosis as rescue therapy. RTX was administered according to "standard regimen" (4 weekly 375-mg/m2 infusions) in all subjects. The mean age of patients at the beginning of RTX treatment was 52 years (range 25-82 years). The mean duration of available follow-up was 18 months (range 3-60). Five patients (5/20; 25%) did not receive any prophylaxis against antiviral and antifungal infections and 2 patients discontinued prophylaxis within first week due to allergic reactions. Two of the five patients that did not receive the prophylaxis had the lower median age and 3 patients presented only hypertension as comorbidity. Overall 11 (11/20; 55%) patients received PJ prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX) and 10 (10/20; 50%) received HZV prophylaxis with acyclovir. Generally, prophylaxis was maintained for 12 months following the first infusion of RTX. Eight subjects received TMP/SMX 960 mg b.i.d twice weekly, 5 patients received 960 mg 3 times a week. Acyclovir was administered at a dose of 200 mg twice daily every day in all subjects. The mean value of ALC before and after RTX was 2529/mmc (range 1100-5420) and 1939/mmc (range 670-3930), respectively (Table 1). Only 3 patients showed ALC < 1000/mmc after the 4th course of RTX treatment. ALC was however in the normal range after a mean of 4 months after the end of RTX treatment in all cases. Electrophoretic proteinogram was available for 8 patients. No substantial decrease in gamma globulin level during follow-up was observed up to one year after RTX. The mean value of gamma-globulin was 10,9 g/dl (range 7-19) and 10,5 g/dl (7-11,8) respectively before and after RTX. Overall, no clinical signs of infections by PJ, HZV and HSV were reported in the analysed cohort of patients, moreover hospitalization or laboratory analysis for any suspected infection during the available follow-up was not required in any case
Conclusions
In our analysis, 11/20 (55%) patients of the cohort examinated received prophylaxis. Among the group who did not receive prophylaxis, these patients had a lower median age and one comorbidity only. In general, laboratory parameters did not show any persistent abnormality, neither clinically diagnosed infections occurred.Although the relatively small number of patients evaluted, the current analysis shows that prophylaxis against PJ and HZV infections is frequently adopted for ITP subjects receiving RTX and its potential beneficial effect. The role of prophylactic treatment to prevent viral and fungal infections in patients with ITP after RTX is far from being well-defined.

Disclosures
No relevant conflicts of interest to declare.