Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features

Abstract

Background: The boundaries between myelodysplastic syndromes (MDS) and immune-mediated cytopenias are often difficult to establish and both conditions may benefit from immunosuppressive therapy. The optimal timing and doses of immunosuppressants are largely unknown.

Materials and methods: We systematically evaluated a retrospective cohort of 79 patients with low-risk MDS tested for anti-erythrocyte or anti-platelet autoantibodies to assess their frequency and the efficacy of immunosuppression, particularly with steroids.

Results: We found autoantibody positivity in 43% of cases and overt autoimmune diseases in 18%, including autoimmune hemolytic anemia, immune thromboctyopenia, and Evans syndrome. Steroid treatment improved cytopenia in about half of patients, with 26% achieving a complete recovery lasting for a median of 12 months. Better responses were observed in anemic patients with anti-erythrocyte autoantibodies than in those with anti-platelet autoantibodies, and the combination with recombinant erythropoietin (7/10) had a possible synergistic effect. Steroid doses were heterogeneous depending on the clinical intent (i.e., anti-inflammatory, immunosuppressive, anabolizing). Patients treated with a dose of 1 mg/kg day of prednisone for overt autoimmune cytopenia showed high rates of complete responses (60%).

Discussion: This observation suggests a trial with a short course (2-3 weeks) of standard steroid doses to ascertain efficacy and properly silence the autoimmune pathogenic mechanism. Steroid-related adverse events (16% of cases) should be monitored carefully in this elderly, frail population. In conclusion, features of autoimmunity are present in more than two-thirds of low-risk MDS patients and a trial with prednisone 0.5-1 mg/kg day for 2-3 weeks, with proper monitoring of adverse events, may be useful to improve cytopenias in selected cases.

Figure 1

Disposition of autoimmune markers and diseases among patients with low-risk myelodysplastic syndromes LR MDS: low-risk myelodysplastic syndrome; Ab: autoantibodies; anti-PLT: anti-platelet autoantibodies; ITP: immune thrombocytopenia; DAT direct antiglobulin test; AIHA: autoimmune hemolytic anemia; ES: Evans syndrome; hypo-MDS hypocellular myelodysplastic syndrome.

Figure 2

Paradigmatic cases of low-risk myelodysplastic syndrome receiving therapy for immune mediated cytopenia AIHA: autoimmune hemolytic anemia; ITP: immune thrombocytopenia; ES: Evans syndrome; MDS: myelodysplastic syndrome; Pred: prednisone; LEN: lenalidomide; rEPO: recombinant erythropoietin; EPAG: eltrombopag; PR: partial remission; CR: complete remission.