Lower-dose anti-thymocyte globulin effective in aplastic anaemia


21 Jul 2016

Comparison of dosing schedules at two Brisbane hospitals has suggested that a low-dose regimen of anti-thymocyte globulin in patients with aplastic anaemia may be as effective as standard higher doses, and potentially reduce the risk of adverse side effects.

Dr Ashleigh Scott and colleagues compared 14 patients treated with 40 mg/kg on days 1 to 4 and another 17 patients treated with 15 mg/kg on days 1 to 5.

The different regimens had been used historically at the Princess Alexandra Hospital and the Royal Brisbane and Women’s Hospital. All other aspects of care, including concomitant cyclosporin and methylprednisolone, were thought to be similar.

There were no significant differences in the rates of response (64% vs 71%), relapse (33% vs 33%), transformation to myelodysplastic syndrome or related disorders (14% vs 24%) and infection (43% vs 47%) in the standard and low-dose cohorts, respectively.

“Our data suggest that use of lower-dose anti-thymocyte globulin schedules in first-line treatment of aplastic anaemia provides non-inferior rates of response, relapse and survival,” Dr Scott and colleagues wrote in the Internal Medicine Journal.

“Given that a significant proportion of newly diagnosed patients will be ineligible for first-line transplantation, further prospective research is warranted to confirm these results.”

Use of the two markedly dosing schedules may have arisen from the availability of two commercial anti-thymocyte globulin products: ‘Lymphoglobuline’ had been used at the lower dose, mainly in Europe until it was withdrawn from the market, while ‘ATGAM’ had been used at the higher dose, mainly outside Europe and particularly in the United States and Australia.

Anti-thymocyte globulin is an inherently heterogeneous compound produced in horses, the authors said. It is a polyclonal agent with a broad antigen specificity, created by inoculating animals with human cells such as thymocytes or thoracic duct lymphocytes.

“To date there are no published dose-finding studies of ATGAM in particular in aplastic anaemia, and nor are there published prospective studies comparing different equine anti-thymocyte globulins in aplastic anaemia.

“Importantly, our outcomes in both dosing schedules appear to correlate with those of the major clinical trials, which demonstrates overall response rates of 60-80%, and 5-year overall and event free survival rates of approximately 75% and 35-50% respectively.”

Younger patients with aplastic anaemia are usually treated with sibling allogeneic haematopoietic progenitor cell transplant, achieving response rates and overall survival in about 90% of cases.

“However, for patients >40 years old, or when a suitable donor is not available, immune suppressive therapy is recommended,” they said.

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