Outcomes and mutational analysis of patients with lower-risk non-del5q myelodysplastic syndrome treated with antithymocyte globulin with or without ciclosporine A. (August 2018)

• Record Type: Journal Article
• 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.
• Is Part Of: Leukemia research. Volume 71(2018)
• Page Start: 67
• Page End: 74
• Publication Date: 2018-08
• Subjects: Immunosuppressive treatment -- Antithymocyte globulin -- Ciclosporine A -- Eltrombopag -- Somatic mutations; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.05.007
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: 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. Abstract: 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.