Autoimmune Hemolytic Anemia Associated With Myelodysplastic Syndrome: A Case Report

Abstract

Myelodysplastic syndrome (MDS) represents a spectrum of myeloid disorders occasionally linked to autoimmune diseases. Here, we present a case of a 60-year-old man demonstrating an unusual coexistence of MDS with warm-autoantibody autoimmune hemolytic anemia (wAIHA). Diagnostic evaluation, including positive direct antiglobulin testing, confirmed the autoimmune etiology of his anemia despite his low-risk MDS classification. Prompt initiation of prednisone therapy resulted in significant hematological and clinical improvement, allowing for a conservative management approach without transfusion requirements. This case underscores the importance of identifying the relationship between wAIHA and MDS, particularly in low-risk scenarios. Moreover, these findings suggest the efficacy of corticosteroids in managing autoimmune anemia in the context of concomitant wAIHA and MDS.

Introduction

Myelodysplastic syndromes (MDS) are a group of myeloid disorders characterized by ineffective hematopoiesis, leading to peripheral blood cytopenias. ¹ While these syndromes are frequently linked to autoimmune disorders, the co-occurrence of MDS with autoimmune hemolytic anemia (AIHA) remains relatively uncommon, with reported incidences accounting for only approximately 1% of cases.^2,3 In this case, we describe a patient who presented with pancytopenia and was found to have MDS and AIHA.

Case Report

A 60-year-old man was referred to the hematology clinic for the assessment of pancytopenia, accompanied by complaints of persistent fatigue over the preceding months. His medical history included hypertension, hyperlipidemia, and hyperuricemia. The patient denied experiencing abnormal bleeding episodes or infections. On admission, his vital signs and physical examination yielded unremarkable results.

The initial complete blood cell count revealed a white blood cell (WBC) count of 2.64 × 10⁶/L, a neutrophil count of 1.37 cells/µL, a hemoglobin concentration of 7.0 g/dL, a platelet count of 69 000 × 10⁶/L, and a reticulocyte count of 10.09%. Additional laboratory findings included a lactate dehydrogenase level of 226 U/L and an elevated total bilirubin level of 2.4 mg/dL.

Subsequently, the patient’s hemoglobin decreased to 6.8 g/dL over the ensuing days. A comprehensive hemolytic anemia workup revealed an elevated lactate dehydrogenase of 231 U/L and a haptoglobin level less than 30 mg/dL. The direct antiglobulin test (DAT) returned positive for anti-IgG and anti-C3 complement antibodies, indicative of warm-autoantibody autoimmune hemolytic anemia (wAIHA).

A bone marrow biopsy was conducted, revealing hypercellular bone marrow with megakaryocyte and erythroid dysplasia, fibrosis, and 2% blasts, consistent with MDS with fibrosis. Cytogenetic analysis yielded negative results for any mutations.

In response to the diagnosis, the patient received a transfusion of 1 unit of packed red blood cells and started treatment with 60 mg of prednisone. Following a 2-week treatment period, significant improvement in the patient’s hematological parameters was observed, with a hemoglobin level of 12.2 g/dL, a WBC of 8.7 × 10⁶/L, and a platelet count of 128 000 × 10⁶/L. Both the lactate dehydrogenase (145 U/L) and haptoglobin (81 mg/dL) levels returned to within the normal range.

Discussion

Autoimmune hemolytic anemia is a rare disease with an estimated annual incidence of 1–3 cases per 100 000 individuals. Diagnosis is typically confirmed through a positive DAT for IgG and/or C3d antibodies. ⁴ In the context of MDS, AIHA is predominantly observed in patients classified as having low-risk MDS. ⁵

The assessment of disease risk in MDS is based on the Revised International Prognostic Scoring System (IPSS-R), which categorizes patients into 5 prognostic risk groups. These groups are determined based on factors such as blood cell counts, the bone marrow blast ratio, and cytogenetics, with each category linked to a different expected median survival. ⁶

According to the IPSS-R score, the patient received a score of 3.0, comprising 1.0 for cytogenetics, 1.5 for hemoglobin <8.0 (g/dL), and 0.5 for platelets between 50 and 100 (×10⁹/L). Consequently, his disease was classified as low risk, with a predicted median survival of 5.3 years. ⁶ Notably, half of the patient’s score is attributed to anemia, and the reduction in red blood cells was secondary to AIHA, not primary MDS. Therefore, following treatment with steroids, the patient’s IPSS-R score could change. With a revised score of 1.0 (attributed solely to cytogenetics), the prognosis improved, resulting in a median survival estimate of 8.8 years. ⁶ This finding demonstrates the impact of diagnosing AIHA and the importance of therapeutic interventions in influencing prognostic assessments for individuals with MDS.

According to the National Comprehensive Cancer Network (NCCN) guidelines for low-risk MDS and no cytogenetic abnormalities or ring sideroblasts <15%, patients with symptomatic anemia are typically subjected to an erythropoietin (EPO) test to explore the possibility of treatment with an EPO-stimulating agent. ⁷ Nevertheless, our patient was diagnosed with anemia primarily stemming from an autoimmune etiology rather than the MDS itself. Consequently, the therapeutic approach deviates from the conventional course, leading to the initiation of steroid therapy to specifically target the autoimmune hemolytic component.

Corticosteroids are the first-line therapy for warm antibody-mediated autoimmune anemia and are typically initiated at a dose of 60 to 100 mg or 1 to 1.5 mg/kg body weight per day of prednisone or its equivalent. This dosage has demonstrated efficacy in inducing complete remission in more than half of the patients.^8,9 A response to steroids is observed in approximately 80% of patients, marked by a sustained increase in hemoglobin levels exceeding 10 g/dL, typically manifesting within 2 to 3 weeks.^10,11 The standard course of treatment spans a minimum of 6 months. ⁹

While initial responses to steroid therapy are often positive, the potential for treatment failure may require alternative interventions, such as rituximab.^10-12 However, it is noteworthy that in reported cases where complete resolution of anemia occurred following corticosteroid treatment, these medications were frequently administered alongside recombinant EPO.^13,14

In our patient’s case, the therapeutic approach aligned with standard practice, starting with prednisone. However, given the improvement in the patient’s anemia and the absence of transfusion requirements, along with his low-risk MDS status, the current management strategy leans toward conservative observation without systemic therapy. This decision considers the patient’s overall disease prognosis and current clinical status. Subsequent therapeutic decisions will be guided by regular monitoring of blood counts and disease progression, ensuring that treatment is tailored to the patient’s clinical condition.

Conclusions

This case highlights the rare co-occurrence of MDS with AIHA, emphasizing the complexities in the presentation and management of hematologic disorders. The successful treatment of the patient’s anemia with corticosteroids underscores the importance of accurate diagnosis and appropriate therapeutic intervention, which can significantly influence prognosis. This case illustrates the need for a thorough diagnostic approach in patients with MDS and cytopenias, as identifying secondary causes like AIHA can alter management strategies and improve patient outcomes.