Case history
A 70-year-old woman, followed at our institution for CMML associated with wAIHA, was admitted at hospital for dyspnea and malaise in March 2017. At the time of CMML diagnosis 15 years earlier, in 2002, she presented with splenomegaly, oral lichen planus and IgG-mediated wAIHA. At that time, bone marrow examination did not show excess of blasts and karyotype was normal. CMML did not require any treatment by itself but treatment for symptomatic anemia was initiated. AIHA responded initially to prednisone (1 mg/kg/day) but relapses were frequent during tapering and the patient experienced many steroids complications. Mycophenolic acid failed to control the hemoglobin level and the patient required repeated packed red blood cells (PRBC) transfusions. A splenectomy was performed in 2007, leading to a prolonged control of AIHA. The hemoglobin level remained stable between 100 and 110 g/L until 2015, although haptoglobin level was repeatedly below the normal range, and then it gradually decreased. In the meantime, hydroxyurea had been initiated in June 2008, because of increasing leukocytosis. Treatment with recombinant erythropoietin was initiated in November 2016, because anemia was thought to be more related to bone marrow failure than hemolysis at that time. Erythropoietin was ineffective as well as prednisone which was resumed at the beginning of 2017. The patient received several RBCP transfusions, especially after hip prosthesis for intercurrent femoral neck fracture, but their efficacy was very transient. Thrombocytopenia then developed for the first time in the history of the disease. At admission in March 2017, hemoglobin level was 63 g/L with reticulocytes count 227 G/L, platelet count was 61 G/L and white blood cells were 23 G/L with 22% monocytes and 15% myelocytes and metamyelocytes. There were both elevation of LDH level (1.5 x UNV) and decreased haptoglobin level (< 0.10 g/L). Direct antiglobulin test (DAT) was positive for IgG (strong) and C3d (low). Bone marrow aspiration showed both erythroblastic and monocytic hyperplasia without blast excess, thus eliminating leukemic transformation. The megakaryocytes were normally present, suggesting that thrombocytopenia was related to peripheral destruction of platelets. Screen for cold agglutinins and a paroxysmal nocturnal hemoglobinuria (PNH) clone was negative. The diagnosis of Evans syndrome was established. The dose of prednisone was increased to 2 mg/kg/day and the patient then received, within a short period of time, daily boluses of high-dose methylprednisolone (500 mg/day for three days), intravenous immunoglobulins (1 g/kg/day for two consecutive days) and four infusions of rituximab (375 mg/m² weekly). All these treatments failed and several plasma exchanges were performed, due to poor anemia tolerance with a hemoglobin level of 31 g/L at nadir. Despite all these procedures, hemoglobin level did not improve nor stabilize. About one month after the last infusion of rituximab, a treatment with eculizumab was started. The patient received 600 mg of eculizumab every week for four weeks and then 900 mg every two weeks. After starting eculizumab, hemoglobin and platelet levels gradually increased. Three months later, hemoglobin has stabilized around 10 g/L, while the platelet and LDH levels were normalized (table 1). For the first time in her medical story, the haptoglobin level went back to near normal values. The infusions of eculizumab were progressively spaced out and then definitively stopped in July 2018, after 14 months of treatment. With a follow-up of 12 additional months, no recurrence of AIHA has occurred.