DP062 | MIXED TYPE AUTOIMMUNE HEMOLYTIC ANEMIA: A SINGLE CENTER OBSERVATIONAL STUDY

Mixed autoimmune hemolytic anemia (mAIHA) is a rare form of AIHA with combined warm react-ing IgG autoantibodies and cold agglutinins. Diagnosis requires direct antiglobulin test with mono-specific antisera, autoagglutination at 20°C and cold agglutinin titer. Treatment of mAIHA remains non-standardized with case-by-case management and no trials ongoing. We present a retrospective observational study of 63 mAIHA patients from 299 AIHA cases followed at a tertiary Hematologic Center in Milan (1999-2024). We collected clinical features, therapy lines, responses (ORR: Hb > 10g/dL and increase > 2 g/dL from baseline), complications and outcome. Clinical features and out-comes of mAIHA were compared with those wAIHA and CAD patients. Patients were mainly fe-males, median age 54 years (9-83) with 54 month median follow up (1-217), Table 1. Median Hb at presentation was 7.1 g/dL (2.9–11.5), with 68% having Hb < 8 g/dL and 32% < 6 g/dL. Transfusions were required in 43%. Median LDH was 4.1× ULN (1.2–12) and 55% showed inadequate reticulo-cyte response. Evans syndrome occurred in 11%. Patients received a median of 2 (1-6) therapy lines, with 70% requiring >1 treatment and 35% >2. Treatment included steroids (92%, ORR 83%), rituxi-mab frontline (13%, ORR 100%), rituximab in later lines (33%, ORR 90%) and cytotoxic immuno-suppressants (41%, ORR 77%). Six% of patients received erythropoietin stimulating agents, and 17% underwent splenectomy (ORR 91%). During follow up, 16 patients (25%) experienced infectious complications, mainly grade 2, and thrombosis occurred in 4 (6%). Overall, 9 patients died, 2 of which due to AIHA complications (multiorgan failure and sepsis in a splenectomized patient). mAIHA patients exhibited a trend toward a higher incidence of severe anemia compared to wAIHA and CAD (Hb < 6 g/dL: 32% vs. 26% vs. 8%, p = 0.08), with no significant difference in transfusion requirements (43% vs. 38% vs. 40%). Moreover, mAIHAs more frequently required >2 treatment lines (68% vs. 37% vs. 50%, p = 0.001) and had more infections (25% vs. 15% vs. 11%, p = 0.05), whereas thrombotic events (6% vs. 14% vs. 14%, p = NS) and AIHA-related mortality (3% vs. 2.5% vs. 2%, p = NS) were comparable among groups. In conclusion, mAIHAs often have very severe clinical presentation, require multiple therapy lines and display frequent infections complications. While new therapies are being investigated for wAIHA or CAD, treatment of relapsed/refractory mAIHA remains an unmet need.