Splenectomy and partial splenectomy improve hematopoietic stem cell engraftment in hypersplenic mice.

Abstract

BACKGROUND: Hematopoietic stem cell (HSC) engraftment is delayed after transplantation in children with hypersplenism, increasing the morbidity and costs of care. Preliminary clinical data suggest that splenectomy before HSC transplantation may improve HSC engraftment, although this observation has not been tested in an animal model. METHODS: We performed total splenectomy (n = 22), partial splenectomy (n = 16), or sham laparotomy (n = 21) on erythrocyte protein 4.2 knockout mice, a murine model of hereditary spherocytosis with hypersplenism. After 10 days, we lethally irradiated the mice, transplanted 3 x 10(6) allogeneic bone marrow cells, and then assessed engraftment using serial complete blood counts. Successful engraftment was defined as recovery of hemoglobin, neutrophil, or platelet counts. We compared engraftment rate using chi(2) test and time to engraftment using Student's t test analysis, with significance defined as P < .05. RESULTS: Total splenectomy increased the rate of successful HSC engraftment and decreased the interval to HSC engraftment compared with controls. Similarly, partial splenectomy decreased the interval to HSC engraftment, with a nonsignificant trend toward improved overall rate of successful HSC engraftment. CONCLUSION: Partial or total splenectomy before HSC transplantation improves HSC engraftment in hypersplenic mice. This model supports consideration of splenic resection in hypersplenic children requiring HSC transplantation.