63P - Addition of human chorionic gonadotropin to the current standard mobilization approach with granulocyte-colony stimulating factor increases overall survival in a murine model of peripheral blood stem cell transplantation: Are we far enough for therapy?

Background

One important limitation of the current standard approach of mobilizing hematopoietic stem cells (HSCs) in the peripheral blood (PB) using granulocyte-colony stimulating factor (G-CSF) for the prophylaxis of chemotherapy induced febrile neutropenia or in donors for PB stem cell transplantation (PBSCT) is insufficient mobilization. Based on our preliminary results on the effect of human chorionic gonadotropin (HCG) on stimulating the peripheral mobilization of HSCs in vivo, the aim of the current study was to assess the effect of the addition of HCG to mobilization with G-CSF on the overall survival (OS) as the primary endpoint in a mouse model of PBSCT.

Methods

Male donor mice (n=20) were pretreated with a single dose of either peg-G-CSF alone (group A, n=10) or HCG + peg-G-CSF (group B, n=10), 5 days prior to PBMC harvest. PBMCs were immediately transplanted to the equivalent number of Busulfan mieloablated female mice by intravenous tail injection and OS was assessed in both recipient groups.

Results

The median OS in the group of recipients transplanted with peg-G-CSF mobilized PBMCs (group A`) was 81 days. In the recipients transplanted with HCG+ peg-G-CSF mobilized PBMCs (group B`} the median OS is not reached at 154 days with 90% of the recipients still being alive.

Conclusions

Addition of HCG to the current standard mobilization approach with G-CSF in donors has almost doubled the survival rate in the recipients of a murine model of PBSCT with the median OS not yet reached after 154 days. This prompts for the translation of the preclinical study`s approach in a human proof-of-principle/feasibility clinical trial.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Executive Agency for Higher Education, Research and Innovation Funding (UEFISCDI), Ministry of National Education (MEN), Romania.

Disclosure

All authors have declared no conflicts of interest.