European Multi-Centre Study on the Use of Anti-Thymocyte Globulin in the Treatment of Myelodysplastic Syndromes.
Authors: Lim ZiYi , Killick Sally , Cavenagh Jamie , Bowen David , Culligan Dominic , Bacigalupo Andrea , Marsh Judith , Mufti Ghulam 
Published: April 2020

Abstract
In patients with myelodysplastic syndromes (MDS), there is increasing evidence to suggest that immunological dysregulation plays an important role contributing to ineffective haematopoiesis and progressive cytopenias. Several studies have suggested that a sub-group of patients with low-risk MDS may respond to treatment with anti-thymocyte globulin (ATG). The characteristics of this group are still being defined.
We reviewed the outcomes of 68 patients with MDS treated with ATG in the United Kingdom and Italy. All patients received a single treatment course of lymphoglobuline (Sangstat-Genzyme) (1.5 vials/10 kg/day for 5 days;1 vial contains 100mg protein). The study end-point was response at 6 months. Haematological response was assessed as per the Cheson criteria. The median age of the patients was 51.5 years (range: 19–75). There were 40 (59%) male and 28 (41%) female patients. The diagnosis as defined by FAB classification was refractory anaemia (RA) n=53, refractory anaemia with ring sideroblasts (RARS) n=4, and refractory anaemia with excess blasts (RAEB) n=11. IPSS was low n=3, Int-1 n=53, Int-2 n=5, high n=4. 19/54 patients had a normocellular/hypercellular bone marrow, 35/54 patients had a hypocellular bone marrow. Cytogenetic risk as defined by IPSS was low n=50, intermediate n=8, high n=6. HLA-DR15 was available in 27 patients, of which 10 were positive. Only 1 of 23 patients tested for the presence of PNH clone was positive. 61/68 patients were blood transfusion dependent and 31/68 were platelet transfusion dependent at time of treatment. The median duration from diagnosis to treatment with ATG was 13 months (range: 0.5–342).
30/68 (43%) patients had a partial or complete response to ATG. The median age of responders was 49.5 years (range: 19–73). At 6 months assessment, 26/30 patients had a erythroid response (20 major, 6 minor), 10/30 patients had a neutrophil response (8 major, 2 minor) and 20/30 patients had a platelet response (12 major, 8 minor). The median duration of response was 29 months (range: 2–83). 6/30 (20%) patients (3 RAEB, 3 RA) relapsed after initial response to ATG with 3 patients progressing to AML (2 RAEB, 1 RA). There was no significant difference in age, time from diagnosis to treatment, bone marrow cellularity, FAB classificiation, cytogenetic risk or HLA-DR15 status between responders and non-responders. However, responders to ATG had a more favourable IPSS (Low, Int-1 as compared to Int-2, High) (p=0.03). The 3 year actuarial overall survival between responders and non-responders is 87% vs 40% (p=0.01). On univariate analysis, response to ATG, IPSS, and FAB classification were strongly associated with overall survival, however on multivariate analysis, IPSS was the only independent variable for overall survival (p&lt;0.01 HR 3.46 95%CI 2.01–5.94).
A single course of ATG can induce durable haematological responses in a significant proportion of patients with MDS, with improved overall survival. ATG should be considered as a treatment option in patients with low IPSS.