Evidence based use of erytrhopoietin in patients with autoimmune hemolytic anemia: a multicenter international study

Bone marrow reticulocyte compensation in autoimmune hemolytic anemia (AIHA)is a recently recognized determinant of outcome.Erythropoietin (EPO) has been anecdotally used to ameliorate marrow response, but predictors of outcome are not known.In this study we aimed to evaluate EPO efficacy and its predictors in a cohort of AIHA patients. Data on AIHA cases who had received EPO were retrospectively collected using a preformed survey. Efficacy was evaluated at 15 and 30 days, and then at 3,6 and 12 months; Hb response was considered partial (PR, >2 g/dL Hb increase or >10g/dL) or complete (CR, >12g/dL). 29 cases followed from Jun 2007 to Feb 2019 at 7 centers in Italy, France, Norway, Austria, and UK were included. Main AIHA types (warm, cold, mixed, and DAT negative) were present, and 3 cases were secondary to a lymphoproliferative disorder (1 non-Hodgkin lymphoma, 1 Waldenstrom macroglobulinemia, and 1 chronic lymphocytic leukemia; not active and without specific treatment at the moment of the study). Patients’ characteristics are shown in Table 1: all patients had received at least one previous therapy, and the majority (69%) started EPO because of non-response to ongoing treatment (steroids 15, immunosuppressor 4,sutimlimab 1). 6 patients had received rituximab during the 3 months before EPO start (median 1 month, range 0-5).At EPO initiation, 21% of cases displayed severe anemia, 73% had inadequate reticulocytosis (i.e.BMRI<121)and 89%(of 18 tested) showed inappropriately low endogenous EPO. Patients were treated for a median of 7 months and responses were observed in about 70% of cases at month+1 and +3, with a median Hb and reticulocyte increase of 21.5 (2-48) g/L (p<0.001) and 25(0-220)x109/L at month+1; and 29 (0-66) g/L (p<0.001) and 49 (0-195)x109/L at month+3, respectively. Notably, 64% of patients responded as soon as at day+15; this finding supports a direct activity of EPO although recent/concomitant treatments may have contributed. At last follow up, 13 cases had discontinued EPO: 6 for long standing CR and 7 because of NR(3 with hemolytic flares). Response to EPO was associated to primary AIHA (73 vs 33% in secondary), inadequate reticulocytosis (76 vs 50% with adequate reticulocytosis), and not-warm (85 vs 50% in warm cases) not transfusion dependent cases (76 vs 50% transfusion dependant). In conclusion, EPO is effective in about 70% of AIHA patients unresponsive to ongoing treatments, particularly in cases with inadequate reticulocytosis.