Low Dose Anti-Thymocyte Globulin (ATGAM) As Treatment of Aplastic Anaemia Is Associated with Similar Response Rates and Survival As per Higher Dose Atgam Schedules
Authors: Scott Ashleigh , Mills Anthony K. , Morris Kirk Lachlan , Nakagaki Midori , Kennedy Glen A 
Published: October 2019

Abstract
Background / Aims
Although combination anti-thymocyte globulin (ATGAM®, Pfizer Inc, NY USA) plus cyclosporine (CsA) is standard therapy for aplastic anaemia (AA), there is minimal data available with respect to optimal ATGAM dose in this disorder. Our institutions have used differing protocols incorporating equine ATGAM at either 40mg/kg/day D1-4 (160mg/kg; standard dose) or 15mg/kg/day D1-5 (75mg/kg; lower dose), in combination with identical CsA and methylprednisolone schedules as treatment of AA where first-line sibling allograft was unavailable. We aimed to review the outcome of AA patients treated with these different ATGAM dose schedules at our institutions.
Methods
All patients >16yrs who received ATGAM for AA between January 2002 and December 2013 were identified from institutional data bases. Diagnostic details and clinical outcomes were determined by retrospective review of individual medical records. Aplastic anaemia severity and response to ATGAM / CsA were defined as per EBMT criteria (Blood 2003; 101: 1236). The primary outcomes were overall response (CR / PR), relapse rate (RR), transformation into AML / MDS and overall survival (OS).
Results
A total of 31 patients were identified, including 14 (45%) treated with standard dose ATGAM and 17 (55%) treated with the low dose schedule. Overall 7% (1), 86% (12) and 7% (1) were classified as non-severe, severe and very severe AA in the standard dose group, and 17% (3), 71% (12) and 12% (3) in the low dose group respectively (p=?NS). Median age at diagnosis was similar between groups; 36yrs (range 23-63ys) for standard vs 44yrs (range 17-80yrs) for low dose ATGAM respectively. At a median time to treatment of 17 (range 5-2084 days) vs 11 days (range 5-1877 days) respectively, overall response was similar between groups: 64% (CR=1; PR=8) for standard vs 76% (CR=5, PR=8) for low dose ATGAM schedules (p=0.69). Median time to best response was also no different between ATGAM treatments: 81days (range 50-164 days) for standard vs 91days (range 48-2133 days) for low dose ATGAM respectively. Although RR was identical between groups (33% vs 30%; p=1.0), median time to relapse was significantly shorter post the lower dose schedule (median 11nths vs 5mths for standard vs low dose ATGAM respectively. Post-ATGAM transformation into AML / MDS occurred in 3 patients in the standard dose group (21%) at a median of 23 mths post therapy (range 19-71 mths) vs 18% (n=3) in the low dose group at a median of 59mths (range 3-81 mths).
Response to 2nd line treatment (rabbit ATG / alloSCT) for non-response or relapse was also similar; 40% vs 50% for standard vs low dose ATGAM respectively (p=1.0). At a median follow up of 25mths (range 6-122 mths) vs 22mths (range 7-99 mths) respectively, OS is identical between groups (71% vs 71% for standard vs low dose ATGAM respectively, p=1.0)
Conclusion
Our experience suggests that low dose ATGAM at 15mg/kg/day D1-5 as treatment of AA produces similar responses and outcomes as per standard dose ATGAM scheduling. Prospective trials comparing ATGAM dose schedules in AA are warranted.

Disclosures
Off Label Use: Off-label: Horse ATG (ATGAM), rabbit ATG (Thymoglobuline), Cyclosporin, Alemtuzumab and Eltrombopag are all used off-label for treatment of Aplastic Anaemia in Australia..