On behalf of our co-authors, we would like to thank Drs Shaw and Bleakley for their comments on the subject of CD34 selection in hematopoietic stem cell transplantation (HSCT) for metabolic disorders. The primary aim of our study was to demonstrate that bone marrow can be processed with the CliniMACS device, and that the final product can be safely used to perform HSCT in children.1 Drs Shaw and Bleakley confirm the feasibility and reproducibility of the procedure in patients with hemato-oncological diseases. We would emphasize that the goals of HSCT in lysosomal diseases are not only survival but also stabilization or enhancement of the neuropsychological function stemming from repopulation of the recipient with metabolically normal donor marrow-derived cells. This includes replacement of non-neuronal cells in the central nervous system. Unlike patients with hemato-oncological diseases, partial chimerism should not necessarily be considered a failure, since there are many Hurler patients with stable partial chimeric engraftment, who are experiencing benefits including neuropsychological developmental trajectories that are comparable to those observed in patients with full chimerism. To date, 11 patients with differing lysosomal diseases have been transplanted at the Center in Monza, six of them with MPS-IH. Among the five survivors with MPS-IH, two patients achieved mixed chimerism and one patient experienced full donor chimerism after their first HSCT. Two patients were full donor chimera after the second HSCT. All patients, including those with partial chimerism, have been continuing to show significant improvements in their medical conditions and neurocognitive status. We agree that TCD, though effective in reducing the risks of GvHD, could add to the risk of graft failure related to the underlying disease; however, GVHD is correlated with a poorer neuropsychological outcome in these patients.2 Therefore, we will continue to follow our procedure that includes TCD for these patients. Drs Shaw and Bleakley also comment about possible alternative strategies (eg to ‘cytoreduce’ patients prior to transplant). To our knowledge, there are no studies to address this issue in the unique field of lysosomal diseases. No less toxic and less resource-intensive ways than a second unrelated HSCT for Hurler patients who experienced rejection have been available till now. Recently, laronidase was approved in the United States and European Union for use in MPS-I patients. It is possible that enzyme replacement therapy with this agent may enhance both the safety and efficacy of HSCT in MPS-I patients when both therapies are used. This hypothesis is being investigated through specific pilot studies.
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