LAUSR

Dear Editor, Autoimmune hemolytic anemia (AIHA) is an autoantibodymediated anemia in which the immune system attacks and destroys red blood cells. Of patients with AIHA, 70–80% are classified as having warm AIHA (wAIHA) according to the optimal reaction temperature of the antibodies. Glucocorticoids (GCs) are the standard first-line therapy forwAIHA,with a response seen in 75–80%of patients, but only 20–30%of patients obtain sustained remission after GC tapering or withdrawal [1]. For refractory and relapsed patients, the anti-CD20 monoclonal antibody rituximab is the second-line treatment [1–3]. However, themedian response time is 3–6 weeks (range 2–16), which is long for patients with severe anemia related to progressive hemolysis and for patients with autoantibody-induced cross-matching incompatibility. wAIHA is an autoimmune disease mediated by autoantibodies, which are produced by plasma cells transformed from B lymphocytes. Rituximab can specifically target B lymphocytes and regulate the immune system. Bortezomib, a proteasome inhibitor, can induce apoptosis of clonal and reactive plasma cells [4, 5]. We speculated that rituximab combined with bortezomib would exert synergistic action on wAIHA by quickly and effectively clearing the B lymphocytes and plasma cells and reducing the production of autoantibodies. Seven patients with refractory or relapsedwAIHAwere treated with rituximab combined with bortezomib between July 2018 and September 2019. AIHA was diagnosed with evidence for hemolysis accompanied by a positive direct antiglobulin test (DAT) and exclusion of alternative causes. Warm AIHA is diagnosed in patients lacking cold associated symptoms with a DAT positive for IgG, IgA (rarely), or C3d ±IgG when a clinically significant cold reactive antibody has been excluded [6]. Indications for treatment of rituximab and bortezomib are as follows: (1) Steroid resistance: patients fail to obtain hematologic response within 3 weeks on at least 1 mg/kg prednisone. (2) Refractory disease: patients fail to respond to at least 2 lines of therapy including prednisone and at least one immunosuppressant. (3) Patients relapse after at least one course of glucocorticoids therapy (HGB < 110 g/L in female and HGB < 120 g/L in male) and glucocorticoids intolerance. Splenectomy was refused according to patients’ own will. The rituximab and bortezomib treatment regimen (RB regimen) is a single dose of 500 mg rituximab (Roche Pharma (Schweiz) AG.) infusion on day 0 and a subcutaneous inject ion of 1.3 mg/m bor tezomib (J iangsu Hansoh Pharmaceutical Group Co., Ltd.) twice a week for 2 weeks on days 1, 4, 8, and 11. Glucocorticoids were tapered rapidly until maintenance of 5~15 mg per day. Oral acyclovir was used to prevent herpes zoster reactivation, and oral sulfamethoxazole was used to prevent Pneumocystis infection. Patient characteristics are shown in Table 1. There were 6 females and 1 male. The median age was 65 years (range, 32 to 76 years). Four patients had idiopathic wAIHA, and two had wAIHA secondary to systemic lupus erythematouswithout other organ involvement except the blood system and one without lymphoma evidence on PET/CT and bone marrow evaluation when diagnosed as wAIHA but relapsed 15 months later with bone marrow biopsy showing B lymphoproliferative disease. One newly diagnosed patient showed no response to standarddose GC after 1 month. The other 6 patients relapsed after 1–5 lines of treatment, with a median history of disease of 29.5 months (range, 9 months to 26 years) (Table 1). The median days to HGB increase > 20 g/L and transfusion independence were 14 days (range, 5–21). Themedian time of * Bing Han [email protected]