Functional Hyposplenism in Pediatric Chronic Graft-Versus-Host Disease

Functional hyposplenism is a well-recognized complication of chronic graft versus host disease (cGVHD). Whether the hyposplenism in cGVHD is transient and if there is any association between the severity of cGVHD and degree of hyposplenism are not well understood. The pitted red cell count has been shown to be a simple and reliable biomarker of splenic function that correlates well to other tests such as quantitative Howell-Jolly bodies and 99mTc sulfur-colloid liver-spleen scans. It measures the ability of the splenic red pulp to pinch off intracellular vesicles, or pits, from red blood cells as they pass through narrow adjustable slits in an endothelial lining.

We hypothesized that functional hyposplenism correlates with the severity of cGVHD in pediatric BMT patients. We performed a single-center, retrospective review of pediatric allogeneic bone marrow transplant (BMT) patients who had more then one pit count performed post-BMT and clinical diagnosis of cGVHD based on NIH consensus criteria.

We identified 9 pediatric BMT recipients (3 males, 6 females; average age at BMT = 9.6 years) that met our criteria. Indications for BMT were AML (2), ALL (1), biphenotypic acute leukemia (1), CML (2) and thalassemia (3). All 9 had functional hyposplenism with active cGVHD as determined by a pit count > 2%. We identified two distinct groups. In 7 of the 9 BMT recipients, there was a return to normal splenic function that lagged between 12 and 18 months after clinical improvement/resolution of cGVHD symptoms and successful weaning of immunosuppressive therapy. In the other 2 patients there was no correlation between abnormal pit count and cGVHD symptoms.

Our single-centre retrospective cohort study provides evidence that the functional hyposplenism associated with cGVHD is not permanent but improvement in cGVHD symptoms and successful weaning of immunosuppressive therapy should not be used as indicators of return to normal splenic function and reasons to stop Penicillin prophylaxis. We propose that all patients post-BMT should have serial pit counts performed, as resolution of cGVHD clinical symptoms does not ensure normal splenic function.

No relevant conflicts of interest to declare.