Immunologic recovery after hematopoietic cell transplantation with nonmyeloablative conditioning

Abstract

Objective: We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning.

Methods: Nonmyeloablative conditioning consisted of 2 Gy total-body irradiation+/-fludarabine and postgrafting cyclosporine and mycophenolate mofetil. All patients received G-CSF-mobilized peripheral blood mononuclear cells. Patients were followed with serial assessments of lymphocyte subset counts, antibody levels, virus-induced lymphoproliferation, and limiting-dilution assays for cytomegalovirus (CMV) T helper (T(H)) cells. Rates of infections over the first year after transplant were calculated.

Results: During the first 180 days, absolute lymphocyte subset counts were similar (except higher total and memory B cell counts on day 80 in nonmyeloablative patients). At 1 year, however, total and naïve CD4 counts, and naïve CD8 counts, were higher in myeloablative patients. The levels of antibodies were similar at all time points and after vaccinations. The function of CD4 cells assessed by virus-induced lymphoproliferation was similar. However, the absolute counts of CMV T(H) cells were higher at days 30 and 90 (p=0.002 and p=0.0003, respectively) after nonmyeloablative conditioning. The rates of definite infections were lower for nonmyeloablative patients during the first 90 days, but were higher later. The higher number of CMV-specific T cells days 30 and 90 after nonmyeloablative HCT coincided with a lower rate of CMV infections during that time.

Conclusion: The immunity of nonmyeloablative HCT recipients appears better than the immunity of conventional HCT recipients early, but not late, after HCT.