DNA synthesis in human blood mononuclear cells correlates with severity of acute graft-versus-host disease

'Spontaneous' blood mononuclear cell DNA synthesis was studied in 83 bone marrow transplantation (BMT) recipients and 58 controls. Prior to BMT, patients with chronic myeloid leukemia had increased DNA synthesis, which decreased dramatically after conditioning and transplantation. After engraftment, patients with syngeneic marrow or allogeneic marrow without graft-versus-host disease (GVHD) had increased DNA synthesis compared to healthy controls. However, patients with acute GVHD (AGVHD) had a significantly increased DNA synthesis compared to patients without GVHD (p less than 0.001). DNA synthesis increased with increasing grade of AGVHD. Among patients with severe AGVHD, recipients of HLA-mismatched marrow had higher lymphocyte DNA synthesis at diagnosis of GVHD and maximum values compared to HLA-matched siblings (p less than 0.05). At diagnosis of GVHD, patients who developed grades II-IV GVHD with progressive disease had higher DNA synthesis, 23.9 +/- 4.0 x 10(3) c.p.m. (mean +/- SE) compared to 11.1 +/- 2.7 x 10(3) c.p.m. in patients in whom GVHD resolved (p less than 0.02). DNA synthesis during GVHD was lower in sheep erythrocyte rosette-forming cells (E-RFC) compared to enriched non-E-RFC. Herpes simplex virus, cytomegalovirus, bacterial septicemia and chronic GVHD had no major effect on lymphocyte DNA synthesis in these patients.