LAUSR

Myelodysplastic syndromes (MDS) are a group of clonal bone marrow neoplasms characterized by ineffective hematopoiesis, manifesting as morphologic dysplasia in hematopoietic cells and peripheral cytopenia(s) [1]. Autoimmune hemolytic anemia (AIHA) is an autoimmune disease (AD) characterized by autoantibodies against erythrocytes, and 10–20% of MDS are accompanied by ADs [2]. Approximately half of AIHA patients have underlying diseases, such as ADs, malignancies, and infections [3]. We report a case of Coombs’ test positive AIHA accompanied by MDS. Azacitidine (AZA) improved the MDS and the Coombs’ test subsequently became negative. Seventy-six-year-old Japanese woman, blood tests revealed hemoglobin (Hb) 8.7 g/dL, hematocrit 29.7%, reticulocyte 8.65 × 104/μL, white blood cell (WBC) 3200/ μL, neutrophils (Neu) 970/μL, platelets (PLT) 14.1 × 104/μL, haptoglobin 103 mg/dL (reference range, 19–170 mg/dL), and WT1 (Wilms tumor 1) mRNA 13,000 copies/μgRNA (reference range, < 50 copies/μgRNA). Bone marrow examination revealed neutrophil hypolobulation and degranulation. However, blasts count was 2.8%, and chromosomal analyses revealed a normal karyotype. The patient was diagnosed with MDS with single lineage dysplasia. Since the Revised-International Prognostic Scoring System (R-IPSS) score was low, follow-up observations were performed. The anemia worsened over 6 months (Hb 7.8 g/dL) and bone marrow examination revealed that the proportion of blast cells had increased to 7.6%. Hence, she was diagnosed with MDS with an excess of blasts. Since her R-IPSS score was high, AZA was administered. Haptoglobin levels decreased to 5 mg/dL. Both the direct and indirect Coombs’ tests were positive, suggesting that MDS was accompanied by AIHA. AZA was administered for MDS. Considering the risk of infections, we decided to monitor the progression of AIHA without immunosuppressive therapy. After the second cycle of AZA, hematological improvement [4] of platelet was achieved. Hematological improvement of erythrocytes was also obtained after the sixth cycle of AZA. WT1 mRNA levels decreased after the first cycle of AZA. Haptoglobin normalized after the sixth cycle of AZA, and both direct and indirect Coombs’ tests became negative after the ninth AZA cycle (Fig. 1). After the 18th AZA cycle, WBC is 3100/μL (blast 0%), Neu 1,150/μL, Hb 8.3 g/dL, PLT 19.2 × 104/μL, haptoglobin 116 mg/dL, and WT1 mRNA 530 copies/μgRNA. Direct and indirect Coombs’ tests remained negative. In previous reports, ADs accompanied by MDS improved after AZA treatment [5, 6]. Few cases of AIHA accompanied by MDS have been reported [7, 8]. Based on previous reports, clinico-laboratory remissions have been obtained with AZA in both MDS and AIHA [9]. This is the first report of conversion of the Coombs’ test from positive to negative after AZA administration. If the hematopoietic clone changes after AZA administration from one that is responsive to autoantibodies to one that is non-responsive, only the direct Coombs’ test becomes negative. Since both the direct and indirect Coombs’ tests became negative, AZA possibly suppressed autoantibody production from MDS-clone-derived B cells [10]. In this case, it’s interesting that AIHA accompanied by MDS was improved by AZA, and the effect was long-lasting. In cases with concomitant MDS and AIHA, administration of AZA for MDS and monitoring the progress of AIHA might be a practical treatment option. * Shinya Yamada [email protected]