Letter to the Editor: Hematopoietic Stem and Progenitor Cell Mobilization and Collection for Patients Diagnosed with Osteopetrosis and Hurler Syndrome

In recent years, an increasing number of gene therapy clinical trials for monogenic diseases have been initiated. Many of these studies employ integration of viral vectors into hematopoietic stem and progenitor cells (HSPCs) obtained by means of peripheral blood (PB) mobilization and apheresis. However, the existing information regarding the feasibility of adequate HSPC mobilization to PB in patients diagnosed with these diseases is in many cases nonexistent, so the designs of these trials are based on general guidelines that may not consistently account for disease-specific characteristics.

Trials such as the current program in Fanconi anemia have been designed intuitively, and stimulating mobilization of HSPCs has been achieved with high doses of granulocyte colony-stimulating factor (G-CSF) because collection difficulties were anticipated due to bone marrow failure. ^{1 –3} Another example of this disease-specific intuitive design is mobilization of HSPCs exclusively with plerixafor in patients with sickle cell disease to avoid the thrombotic risk associated with the use of G-CSF. ⁴

Current gene therapy studies for patients with osteopetrosis and Hurler's syndrome (mucopolysaccharidosis type I [MPS I]) have motivated us to study the mobilizations conducted at our center in these patients for the collection of HSPC as a backup before allogeneic hematopoietic transplantation.

We have reviewed the data related to the mobilization and collection of patients diagnosed with both diseases and we have matched them with the results obtained in healthy donors of similar age and blood volume in ratios of 1:4 for osteopetrosis and 1:2 for those with MPS I. Eight patients diagnosed with MPS I were mobilized with G-CSF at 10–12 μg/[kg·day] for 4 days, generating similar results both in mobilization and collection to those obtained from healthy donors mobilized in a similar manner (Table 1). One patient underwent a second cycle of mobilization after requiring rescue with the first product obtained with G-CSF at 12 μg/12 h for 4 days with a CD34⁺ cell count in PB on the fifth mobilization day of 42 cells/μL (similar to the count of the first process of 34 cells/μL).

At our institution, we do not use mobilization agents for patients diagnosed with osteopetrosis because it is well known that these patients have significant numbers of CD34⁺ cells in PB due to their underlying condition. ⁵ Three patients diagnosed with osteopetrosis also displayed similar results to those of healthy donors even without G-CSF mobilization (Table 1). A fourth patient mobilized in earlier decades with G-CSF at 12 μg/kg for 4 days had a CD34⁺ cell count in PB on the fifth day of 192 cells/μL with 51 × 10⁹/L leukocytes, suggesting that the use of mobilization agents may not be necessary or that more limited mobilization may be feasible. Although generally safe and well tolerated, mobilization agents are nonetheless associated with some adverse events, especially in settings of extensive leukocytosis.

In each of these two series, there were no significant differences in collection-related adverse events relative to those in healthy donors.

In conclusion, we observed that patients with MPS I mobilize HSPCs to PB in similar quantities as healthy donors, and patients with osteopetrosis reach similar PB CD34⁺ counts even in the absence of mobilizing agents. In both patient groups, HSPC collections were performed without specific complications.