Abstract
Treatment of autoimmune hemolytic anemia (AIHA) is complicated by disease heterogeneity and a high propensity for relapse. Most cases of AIHA are mediated by warm and cold-reactive autoantibodies, as defined by the direct antiglobulin test (DAT), and the treatment approach differs depending on the subtype. Evidence supporting use of specific AIHA treatments is limited to retrospective studies, small series, or case studies. To address this issue, a retrospective analysis of all patients with AIHA treated at the Cleveland Clinic from January 2000 to April 2013 was performed.
Patients were included if they were ≥ 18 years old and presented with a new diagnosis or relapse of AIHA. Frequencies of complete responses (CR) or partial responses (PR) were recorded, and the median time to relapse measured using the Kaplan-Meier method. PR was defined as a nontransfused hemoglobin of ≥ 10 mg/dL with a hemoglobin increase of ≥ 2 mg/dL, while CR was defined as a nontransfused hemoglobin of ≥ 12 mg/dL, hemoglobin increase ≥ 2 mg/dL, and normalization of hemolytic markers. The duration of high dose and total corticosteroid therapy was recorded.
180 patients were identified. 122 (69%) presented with warm antibody-mediated AIHA, 42 (24%) with cold antibody-mediated AIHA, 6 (3%) with mixed AIHA, and 8 (4%) with DAT negative AIHA. 97 (54%) were females. 61% of patients were between the ages of 50 and 80. Steroids were used in 82 patients with warm AIHA, 14 patients with cold AIHA, 3 patients with mixed AIHA, and 5 patients with DAT negative AIHA. Steroid response rates were 81% (27% CR, 54% PR) in warm AIHA, 85% (21% CR, 64% PR) in cold AIHA, 66% (33% CR, 33% PR) in mixed AIHA, and 80% (40% CR, 40% PR) in DAT negative AIHA. Median time to relapse was 14.3 months in warm AIHA, 3.6 months in cold AIHA, and 13 months in mixed AIHA; median time to relapse could not be determined in DAT negative AIHA. The mean duration of steroid use was 6.3 months in warm AIHA, 4.3 months in cold AIHA, 5.4 months in mixed AIHA, and 1.5 months in DAT negative AIHA. Rituximab was used in 23 patients with warm AIHA and 14 patients with cold AIHA, with overall response rates of 74% (17% CR, 57% PR) and 80% (27% CR, 53% PR), respectively. The median time to relapse was 8.5 months for warm and 55.2 months for cold AIHA after Rituximab treatment. In 15 patients with warm AIHA, splenectomy induced responses in 83% (33% CR, 50% PR) with a median time to relapse of 37.8 months. In 24 patients with warm AIHA and 7 patients with cold AIHA, treatment of the underlying disorder induced responses in 87% (33% CR, 54% PR) and 86% (29% CR, 57% PR), respectively. Median time to relapse was 22.1 months in warm AIHA and 16.5 months in cold AIHA. Other less commonly used treatments included immunosuppressants, intravenous immunoglobulin, and erythropoietin derivatives, with bortezomib and cold avoidance used in the cold AIHA group. When comparing warm and cold AIHA, no significant difference was found in total response rates to various treatments, including steroids (81% vs. 85%, p = 0.486), Rituximab (74% vs. 80%, p = 0.49), and treatment of the underlying condition (87% vs. 86%, p = 0.662).
This analysis demonstrated a surprisingly high response rate for corticosteroids in all subtypes of AIHA, though most responses in cold AIHA were partial and of relatively short duration. Rituximab was effective in both warm and cold antibody-mediated AIHA, with a high incidence of durable responses in the latter. Definitive treatment of the underlying condition was used less commonly, but was a highly effective approach for treating secondary AIHA. Splenectomy yielded durable remissions in most patients with warm AIHA.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
