Characteristics of diffuse large B-cell Lymphoma patients with rituximab induced acute thrombocytopenia

Abstract Background: Rituximab is a monoclonal antibody that targets CD20-positive B cells. Its combination with the CHOP regimen represents the standard first-line treatment for diffuse large B-cell lymphoma (DLBCL). Previous studies have indicated that rituximab can induce acute thrombocytopenia, occurring in 3-5% of cases. Rituximab induced acute thrombocytopenia (RIAT), a condition lacking a universally accepted definition, typically manifests within the first 1-3 days post-treatment, characterized by a platelet count drop exceeding 50%. However, the extent, timing, and high-risk factors remain insufficiently explored. Aims： This study aims to investigate the clinical features of DLBCL patients with RIAT and analyze their efficacy and prognosis. Methods: This retrospective study analyzed newly diagnosed DLBCL patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine who received rituximab between January 1, 2020, and December 31, 2023. These patients had their blood counts rechecked within 3 days after rituximab administration, and their baseline platelet counts were greater than 50 × 10^9/L. A total of 671 patients were included, of whom 25 (3.7%) experienced a platelet reduction of more than 50% within 3 days after treatment, defined as RIAT. We analyzed the clinical features and prognosis of these patients. Results: Among the 25 patients, 14 (56.0%) were male, with a median age of 66 years (range: 36–93). Nineteen (76.0%) patients were aged ≥60 years. Five (20.0%) patients had Richter transformation to DLBCL. None of the patients had central nervous system (CNS) involvement at diagnosis, and only one patient had CNS relapse. Twenty-three (92.0%) patients were staged as Ann Arbor stage III-IV. Eleven (44.0%) patients exhibited B symptoms. Nineteen (76.0%) patients had an ECOG performance status of 2–4. Thirteen (52.0%) patients had an International Prognostic Index (IPI) score of 4–5. Six (27.3%) patients had bone marrow involvement, and 11 (44.0%) had extranodal involvement at more than one site. No patients had masses larger than 10 cm, and only two had masses greater than 5 cm. The baseline platelet count was 136.0 × 10^9/L (range: 71–237 × 10^9/L), which decreased to 57.0 × 10^9/L (range: 4–98 × 10^9/L) within 3 days, and subsequently recovered to normal levels (100 × 10^9/L) within a median of 16.0 days (range: 2–25 days). One patient experienced lower gastrointestinal bleeding, which resolved with symptomatic treatment, and no deaths occurred during the episode of thrombocytopenia. In the 4-cycle PET evaluation, the complete response (CR) rate was 60.9% (14/23), and the overall response rate (ORR) was 100% (23/23). In the 8-cycle PET evaluation, the CR rate was 72.7% (16/22), and the ORR was 95.5% (21/22). The median follow-up time was 24.2 months (range: 3.4–57.3 months), with six patients relapsing, four deaths, and two lost to follow-up. At the 24-month follow-up, the overall survival (OS) rate was 81.8% (95% confidence interval [CI]: 60.9-93.3%), and the progression-free survival (PFS) rate was 56.0% (95%CI: 34.5-74.7%). Conclusion: In this study, the incidence of RIAT in newly diagnosed DLBCL patients was 3.7%, and patients with RIAT had more risk factors. It is important to note that bleeding events were uncommon, and no deaths occurred during thrombocytopenia. Platelet counts were eventually restored in all patients. Despite the presence of high-risk factors in these patients, poor responses and survival were not observed.