Complete Haematological Response after Low Dose Rituximab in a Patient with Refractory Warm-Type Autoimmune Haemolytic Anaemia
Authors: Peli Annalisa , Malagola Michele , Filí Carla , Skert Cristina , Bergonzi Cesare , Zaja Francesco , Roccaro Aldo M. , Russo Domenico 
Published: April 2020

Abstract
In the last years, the use of rituximab administered with the same schedule used for treatment of B-cell non Hodgkin’s lymphomas (375 mg/sqm weekly for 4 weeks) has been extended to the management of the autoimmune cytopenias, such as the warm-type autoimmune haemolytic anaemia (AIHA). The rational for this therapeutic approach is that B-cell depletion induced by rituximab interferes with the production of autoantibodies against red cells but the mechanism of action has not been completely elucidated and the optimal schedule has not been established yet. In the setting of autoimmune cytopenias, biological and clinical evidences suggest the feasibility of lower doses of rituximab. Low dose schedule of rituximab (100 mg weekly for 4 weeks) was tested in a 78-year old man with a long lasting and symptomatic IgG warm-type idiopathic AIHA who was ineligible to splenectomy and resistant to steroids, immunosuppressive agents and high-dose intravenous immunoglobulins. The absence of an underlying lymphoproliferative disease, the age and the purpose to reduce the immunosuppressive effects were the reasons of our choice. Rituximab were administered intravenously at a dose of 100 mg weekly for 4 consecutive weeks in September 2007. Neither extra-hematological (infusion-related reactions, nausea or infections) nor hematological (leucopenia, neutropenia, and thrombocytopenia) toxicities were observed. The haematological and laboratory data before rituximab were the following: haemoglobin (Hb) 8,9 g/dl (supported with 4 packed red-cell transfusions in the previous 2 months), lactate dehydrogenase (LDH) 250 U/L, indirect bilirubin 3,8 mg/dl, haptoglobin 0 mg/dl, reticulocyte count 84%. Complete response (CR = Hb &gt; 12 g/dl, transfusion independence and absence of clinical and laboratory signs of haemolysis for at least 4 weeks after rituximab treatment, irrespective of direct antiglobulin test positivity) was rapidly achieved at the 6th week and it was maintained until the 29th week. A deep B-cell depletion was documented after 12th week and confirmed at 24th week (CD20 positive cells were uncountable). As frequently observed in the majority of the cases reported in the literature on standard dose rituximab, after 6 months of CR, AIHA relapsed with clinical features and haematological and laboratory signs of haemolysis (Hb 8,3 gr/dl, LDH 170 U/L, indirect bilirubin 2,27 mg/dl, haptoglobin 24 mg/dl and reticulocyte count 35%). A second course of low dose schedule rituximab (100 mg weekly for 4 weeks) was administered and a second CR was documented after 15 weeks. At the last follow up, 23 weeks from the second course of low-dose rituximab (51st week from the first course), the patient is in continuous second CR (Hb 13.9 gr/dl, LDH 150 U/L, indirect bilirubin 0,5 mg/dl, haptoglobin 100 mg/dl and reticulocyte count 1%). As the first course, nor extra-haematological neither haematological toxicities were observed. In particular, although a marked B-cell depletion was continuously documented from the 12th week until the last follow up (51st week), none infective episode occurred. Considering its good safety profile, maintenance therapy with 100 mg of rituximab every 2 months has been planned in attempt to prevent a new relapse. Our report suggests that low dose rituximab could be able to induce a complete and long lasting CR in refractory/relapsed warm AIHA at least as the standard dose. Moreover, low dose rituximab may be effective also after a relapse, but, interestingly, with a slower time of response than the one observed during the first course (6th vs 15th week). Considering the efficacy and the good safety profile, low dose schedule rituximab could be tested in a larger series of patients with warm AIHA and, if the results will be confirmed, it will represent a cheaper and safer treatment than rituximab at standard doses.