A novel IL-11/G-CSF mobilization regimen improves delayed platelet engraftment via targeted megakaryocyte progenitor expansion

Abstract Delayed platelet engraftment (DPE) is a common complication following hematopoietic stem cell transplantation (HSCT) that currently lacks a standard preventive solution. Neither augmenting CD34+ cell mobilization nor thrombopoietin (TPO) administration fully resolves DPE. Our comparative analysis of apheresis products revealed decreased megakaryocyte progenitor (MkP) and megakaryocyte-erythroid progenitor (MEP) cells in DPE patients compared to non-DPE patients. To identify strategies for expanding these progenitor populations, we screened multiple cytokines and plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) using a murine model. Interleukin-11 (IL-11) emerged as the most promising candidate. In vitro colony-forming unit (CFU) assays and murine stem cell transplantation experiments confirmed that IL-11 plus G-CSF expanded progenitor cells retained robust platelet and erythrocyte engraftment potential. We subsequently conducted a prospective clinical trial (ChiCTR2500100054) from July 2022 to July 2025, comparing hematologic engraftment outcomes in autologous HSCT patients mobilized with either IL-11 plus G-CSF (n=137) or G-CSF alone (n=62). The novel IL-11/G-CSF regimen significantly accelerated platelet engraftment (median 14 days vs. 17 days, p=0.006) without affecting granulocyte recovery time (median 12.5 days vs. 12 days, p=0.98). Furthermore, it significantly reduced transfusion requirements for both red blood cells (p=0.004) and platelets (p=0.004). The combination regimen demonstrated a favorable safety profile and was well-tolerated, with no significant differences observed in tumor recurrence, overall survival, or progression-free survival compared to standard G-CSF mobilization. Our findings demonstrate that the IL-11 plus G-CSF mobilization regimen enhances hematologic engraftment, particularly platelet recovery, by increasing the yield of MEP and MkP cells. This represents a promising platform for future stem cell mobilization trials aimed at preventing DPE.