Treatment response, relapse and survival of hospitalized adult primary warm autoimmune hemolytic anemia: A multicenter retrospective cohort study Free

Introduction:

Primary warm autoimmune hemolytic anemia (pwAIHA) is a rare autoimmune disease leading to accelerated red-cell destruction and anemia. Due to its rarity, the treatment choice is based on personal experience and expert guidelines, and evidence on the treatment response, subsequent relapse and prognosis is not well-understood, especially in China, which are important to inform clinical management of the disease. This study aims to inform evidence-based management for wAIHA by describing the treatment response of adult patients hospitalized with pwAIHA and assessing relapse and survival following treatment.

Method:

This retrospective observational cohort study utilized electronic medical records (EMR) from three general hospitals in Shanghai including, Huashan Hospital, the Fifth People’s Hospital of Shanghai, and Shanghai General Hospital. Adult patients hospitalized with a confirmed diagnosis of pwAIHA between January 2014 and March 2024 were included. Patients exhibiting evidence of acquired or hereditary causes of hemolytic anemia were excluded from the analysis. Data on demographic, diagnosis history, hemolysis characteristics, treatment and response were collected from the EMR. Relapse, survival and missing information of response were obtained by physicians through post discharge follow-up phone calls until November 15, 2024. A complete response (CR) was defined as normalization of hemoglobin. A partial response (PR) was defined as an increase in hemoglobin > 20 g/L but not normal and absence of transfusion for the previous 7 days. Relapse was defined as a decrease in hemoglobin > 20 g/L after reaching PR, or a reappearance of wAIHA after reaching CR. A logistic regression model was conducted to investigate the factors associated with relapse. The optimal cutoff point for continuous variables were determined and applied in the models. The age-standardized mortality rate was calculated based on the age composition of the 2020 Chinese National Population Census using direct standardization.

Results:

A total of 104 pwAIHA patients were included, with median age of 63.0 years (IQR 48.8-72.3) at hospitalization and 58.7% comprising female patients. Thirty-nine (37.5%) patients had a previous wAIHA diagnosis and median age was 59.0 years (IQR 44.0-69.3) at the first diagnosis. At study inclusion, a majority of patients (88.3%) had a positive Coombs test. Notably, 84.6% of patients exhibited moderate to severe anemia (<90g/L). Additionally, 85.3%, 91.2% and 84.5% of patients showed elevated reticulocytes (≥ 4%), total bilirubin (≥ 17.1 μmol/L), and lactate dehydrogenase (>250 U/L), respectively, suggesting significant red blood cell destruction. 37.5% of patients had 2 or more comorbidities, with hypertension ranking as the most frequent (18.3%). Almost all patients (94.2%) received corticosteroids as 1L treatment, and only 19 patients advanced to 2L treatment and beyond. Among 93 patients eligible for evaluation, a high response rate (94.6%) is observed with 56 achieved CR and 32 achieved PR, at a median time of 66.0 days (IQR 40.0-145.0) and 14.5 days (IQR 9.0-23.3) after treatment initiation, respectively. Fifty-six patients achieved response had relapse information and about half (53.6%) relapsed, with a median time from response to relapse of 130.0 days (IQR 47.5–480.8). The reticulocyte percentage ≥ 14% at hospitalization (aOR=4.54, p=0.020) was an independent risk indicator for relapse. During follow-up, 33 (31.7%) patients died mostly due to infection (n=21) followed by hemolytic anemia (n=3), cardiovascular disease (n=3) and malignancy (n=3). The age-standardized rate of death was 23.1% (the mortality rate in general population is 0.7%). At 1-, 3- and 5-year post hospitalization, the accumulative death rates were 15.7%, 23.7% and 34.8%, respectively. When considering the whole disease course from 1^st diagnosis, the 1-, 3- and 5-year accumulative death rates were 8.9%, 14.3% and 20.3%, respectively.

Conclusion:

In Chinese patients with pwAIHA, while favorable treatment responses were observed after therapy, there was a notably high rate of relapse accompanied by limited periods of control and poor survival, particularly following hospitalization. This transient relief along with the poor survival outcomes presents a substantial healthcare burden and highlights an urgent need for innovative therapeutic options that can offer more stable and long-term effective treatment for pwAIHA patients in China.