Poor graft function after allogeneic hematopoietic stem cell transplantation is associated with a severely altered bone marrow endothelial microenvironment, as revealed by CD31 expression: An Egyptian single center experience.

INTRODUCTION

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is definitive, potential curative therapy for various hematological diseases. Poor graft function (PGF) remains a significant complication, characterized by persistent cytopenia despite complete donor chimerism. The bone marrow microenvironment, particularly endothelial cells expressing CD31 (PECAM-1), plays a crucial role in the maintenance and proliferation of hematopoietic stem cells. This study examines the expression of CD31 in the bone marrow endothelial microenvironment of patients with Poor Graft Function (PGF) are compared with those exhibiting Good Graft Function (GGF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

PATIENTS AND

METHODS

We conducted a prospective case-control study of 40 patients, equally assigned to the PGF and GGF groups. PGF was defined by persistent neutropenia (ANC <1000/μL), thrombocytopenia (platelets <50,000/μL), and/or hemoglobin levels <8 g/dL during the engraftment, together with hypocellular bone marrow and complete donor chimerism. CD31 expression on stem and non-stem cells in bone marrow specimens were assessed by multiparameter flow cytometry, and the mean fluorescence intensity (MFI) and the percentage of CD31+ cells were quantified. The bone marrow cellularity is typically assessed at our unit typically occurs on day +30 to day +35 during the initial examination.

RESULTS

Individuals with PGF exhibited significantly fewer stem cells (Median 0.295 vs. 0.54, p = 0.003) and CD31+ stem cells (Median 0.31% vs. 0.54%, p = 0.031) compared to those with GGF. Patients with PGF significantly increased MFI of CD31 on stem cells (22.27 ± 5.6 compared to 17.52 ± 4.8, p = 0.007) and non-stem cells (Median 18.1 versus 13.05, p = 0.035). The incidence of ABO incompatibility in PGF was significantly elevated with a serious mismatch rate of 65% compared to 15% (p = 0.001). Positive correlations were noticed between lifespan and the MFI of CD31 on stem cells (r = 0.674, p = 0.001), the quantity of mononuclear cells (r = 0.580, p = 0.007), and the proportion of total CD31+ stem cells (r = 0.448, p = 0.048).

CONCLUSION

CD31 expression patterns reflect significant changes in the bone marrow endothelial microenvironment of PGF patients. The elevated MFI of CD31 in PGF indicates endothelial activation, stress and dysfunction, while the diminished stem cell count implies inadequate support from the hematopoietic niche. The CD31 is identified as a potential biomarker for assessing PGF risk and clarify the etiology of the bone marrow microenvironment dysfunction post-transplantation, as per these findings.