Response: G-CSF and aplastic anemia

We thank Drs Alter and Rosenberg for allowing us to provide more details and precision concerning our recent European survey on the association between the development of MDS and AML and the use of G-CSF in patients with severe AA treated with IST. We already acknowledge that the retrospective, nonrandomized design of our study precludes determining the definitive role, if any, of G-CSF in the genesis of secondary malignancy. However, the large number of patients studied allowed us to estimate the problem and allowed multivariate analysis of risk factors.

Alter and Rosenberg specifically raise the point that the observed association may be the result of “reverse causality” or “confounding by indication” due to G-CSF administration as a consequence of greater disease severity at presentation. Indeed, this was not the case in our survey, since all patients had severe disease (< 0.5 neutrophils/L), and we had observed no evidence of an imbalance of patients with very severe disease (< 0.2 neutrophils/L) in the group that received G-CSF as part of their primary treatment. Thus, our results cannot be explained solely by disease severity.

In this report our goal was to alert physicians that adding G-CSF to IST is currently not standard treatment for severe AA because its usefulness has not been established in this setting, and its role in MDS and AML development is not resolved. This reinforces our view that there is a need for a large randomized trial comparing antithymocyte globulin and cyclosporin with or without G-CSF, which the European Group for Blood and Marrow Transplantation is currently running.