Graft-Versus-Host Disease after Solid Organ Transplant Is Frequently Associated with Bone Marrow Failure and Hemophagocytosis

Introduction Graft-versus-host disease (GVHD) after solid organ transplant (SOT) is a rare complication with high mortality. Unique to SOT is bone marrow GVHD, with most patients dying of bone marrow failure (BMF) and subsequent sepsis. Elevated ferritin has been described as a poor prognostic factor, and there are reports of hemophagocytic lymphohistiocytosis (HLH) after SOT. We reviewed bone marrow aspirate slides of SOT patients with GVHD to determine pathologic features of BMF. Methods Number of hemophagocytic (HP) cells per slide were counted and averaged over two slides, by two independent hematopathologists, and graded as mild (1-4), moderate (5-10), and severe (u003e10) by number of HP cells. Donor and host DNA chimerisms were quantified using polymerase chain reaction, after CD3 and CD33 separation by flow cytometry. Results A total of 9 bone marrow biopsies from 6 patients were reviewed (Table). One patient had serial marrows, with initial count recovery and then subsequent intermittent cytopenias. Five marrows showed evidence of moderate-severe HP; of these, only 1 patient had full count recovery. Increasing donor CD3 marrow, but not peripheral blood chimerisms correlated with BMF. Ferritin levels were not associated with severity of HP (p=0.45), nor with count recovery (p=0.37). Conclusions BMF with increased HP cells is associated with a low likelihood of blood count recovery, and worse prognosis after SOT. Marrow but not peripheral blood donor CD3 chimerisms are prognostic for BMF. Identification of HLH features may guide prognosis and therapeutics in these patients. Further studies are needed to clarify the pathophysiology of SOT BMF, and whether HLH-targeted therapies may improve outcomes.