Does Graft-Versus-Host disease influence the tempo of immunologic recovery after allogeneic human marrow transplantation? An observation on 56 long-term survivors

Abstract

This report describes a study of humoral and cellular immune reactivities in 56 patients who have survived for 1 yr to more than 6 yr after marrow transplantation from an HLA-identical sibling for the treatment of aplastic anemia or hematologic malignancy. All were conditioned for the transplant by high doses of cyclophosphamide and/or total body irradiation. Immunologic studies on the marrow donors served to establish the normal range for the tests used. The influence of an episode of graft-versus-host disease (GVHD) on the subsequent immunologic recovery was emphasized. Thirty-two patients had GVHD, which resolved in 19 and evolved into a chronic form in 13. Tests used included serial determinations of serum immunoglobulins, complement (C3 and C4), lymphocyte counts, T and B cells, lymphocyte responses to allogeneic cells and to mitogens, isohemagglutinin titers, clearance of bacteriophage ∅X174 (phage) from the blood, primary and secondary antibody responses to phage and to keyhole limpet hemocyanin (KLH), and tests of skin reactivity to recall and neoantigens, dinitrochlorobenzene, and KLH. All patients, regardless of whether they had GVHD or not, had pronounced impairment of all immunologic parameters during the first 4 mo after grafting. The speed of immunologic recovery thereafter was faster in patients without GVHD than in those with GVHD. The deficient immune responsiveness in patients with GVHD lasted approximately 2 yr and thereafter tended to persist only in patients with chronic GVHD. A peculiar and unexplained finding in patients with GVHD was significantly higher than normal IgG levels. As a clinical correlate of the prolonged and intense immune deficiency, patients with GVHD showed a tendency toward more frequent and severe infections than those without GVHD. Given enough time, most patients regained near-normal immune reactivity. This occurred much earlier and more frequently in patients without GVHD than in those with GVHD. Patients who regained near-normal immune reactivity did not have unusually frequent infections.