Outcomes and mutational analysis of patients with lower-risk non-del5q myelodysplastic syndrome treated with antithymocyte globulin with or without ciclosporine A

• Published in: Leukemia research Vol. 71; pp. 67 - 74
• Main Authors: Kelaidi, C., Braun, T., Arana, R., Marceau-Renaut, A., Lazarian, G., Soret, J., Cereja, S., Letestu, R., Eclache, V., Lusina, D., Baran-Marszak, F., Ades, L., Preudhomme, C., Martin, A., Fenaux, P., Gardin, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2018; Elsevier
• Subjects: Antithymocyte globulin; Ciclosporine A; Eltrombopag; Immunosuppressive treatment; Life Sciences; Somatic mutations; Ciclosporine A; Eltrombopag; Somatic mutations; Antithymocyte globulin; Immunosuppressive treatment
• ISSN: 0145-2126; 1873-5835; 0145-2126
• DOI: 10.1016/j.leukres.2018.05.007

•Nine out of 20 patients achieved transfusion independence with IST.•TI rate increased with shorter transfusion duration, normal B cells & BM blasts ≤2%.•Mutations were more frequent in patients with normo/hypercellular MDS.•Baseline mutations were associated with a higher incidence of disease progression.
Immunosuppressive treatment is a disease-modifying therapy for lower-risk myelodysplastic syndromes (MDS). However, IST is relatively rarely used and long-term outcomes of patients are seldom reported. We retrospectively studied outcomes of 20 patients with lower-risk non del 5q MDS with transfusion dependency, with horse or rabbit antithymocyte globulin ± ciclosporine A, and frontline eltrombopag in two of them. IPSS-R was low, intermediate and high in 30%, 55% and 10% of the patients, respectively. Fifty-five percent of the patients had hypocellular bone marrow (BM). Baseline mutations were detected in 31.5% of the patients and were more frequent in patients with normo/hypercellular MDS than in patients with hypocellular MDS. Transfusion independence rate for both red blood cells (RBC) and platelets was achieved in 45% of patients. RBC transfusion duration ≤6 months, B-cell counts >0.2 G/L and, marginally, BM blasts ≤2% were associated with higher transfusion independence rate. Age and cellularity did not influence the response rate. Median transfusion independence duration was 53 months. Cumulative incidence of progression to a more aggressive myeloid disease was 0 in patients without baseline mutations and 33% in patients with baseline mutations (P = .008). Median progression-free and overall survival after treatment onset and median overall survival after loss of transfusion independence were 45.5 months, 68 months and not reached, respectively. In conclusion, antithymocyte globulin ± ciclosporine A results in durable responses in MDS, irrespective of age, in patients with lower-risk disease without B-cell lymphopenia and treated early in the course of the disease.