Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s10238-022-00809-0.

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Rituximab is a chimeric monoclonal antibody against CD20 expressed by normal and malignant B lymphocytes. Owing to its effi cacy and low toxicity profi le, the combination of rituximab and chemotherapy has become a standard of care for B-cell malignancies and some autoimmune disorders. Th e most common side eff ects of rituximab include early infusion-related symptoms. Fever, chills and rigors as well as more severe symptoms such as hypotension and bronchospasm occur typically within a few hours of initiation of the fi rst infusion [1]. Th e broad use of rituximab has revealed its less common side eff ects. Delayed transitory neutropenia [2], progressive multifocal leukoencephalopathy, reactivation of hepatitis, interstitial pneumonitis [3] and acute thrombocytopenia [4 -6] have been reported. Here we describe a transient rituximab-induced coagulopathy in a patient with Waldenstr ö m macroglobulinemia (WM) and review previously published cases.A 70-year-old man was admitted to hospital for a recently diagnosed second relapse of WM. Initially, the patient had been treated with chlorambucil, and the fi rst relapse was treated with fl udarabine. Both lines of therapy achieved a response. Th e patient had no medical history of a bleeding tendency. His coagulation tests had been normal before the fi rst manifestation of the disease and were normal when the patient achieved the remission. Second relapse was diagnosed in the local hospital and the patient was referred to the hematology center for intensive care. Immeasurably high paraproteinemia (more than 41 g/L) represented a potential indication for plasmapheresis. Th e procedure was not eventually performed due to the absence of hyperviscous syndrome. On admission, a complete blood count included: white blood cells 2.9 ϫ 10 9 /L (with normal diff erential), hemoglobin 84 g/L and platelets 171 ϫ 10 9 /L. Coagulation studies revealed a prothrombin ratio of 1.31, activated partial thromboplastin time (APTT) ratio of 1.59, fi brinogen 2.9 g/L, antithrombin 63% and normal D-dimer value (420 ng/mL). Th e APTT ratio was fully corrected in mixing studies with normal plasma. With the exception of prolonged bleeding from a trephine biopsy, the clinical status of the patient was normal.Rituximab-containing regimens have become a standard of care for the treatment of WM [7]. Th e patient received rituximab 375 mg/m 2 (day 1), fl udarabine 25 mg/m 2 (days 1 -5) and dexamethasone 20 mg (day 1). Th e administration of rituximab was uncomplicated; the patient exhibited neither infusion-related symptoms (cytokine-release syndrome) nor laboratory fi ndings corresponding to the tumorlysis syndrome. Bleeding from the trephine biopsy ceased spontaneously. However, 4 h after the administration of rituximab, the platelet count started to fall (30 ϫ 10 9 /L). Values reached a nadir (19 ϫ 10 9 /L) 14 h after the administration of rituximab. Th is drop in platelets was part of complex laboratory fi ndings consistent with the diagnosis of disseminated intravascular coagulopathy (DIC). Eightee...