Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma

Abstract

Reconstitution of T-cell immunity after bone marrow transplantation (BMT) is often delayed, resulting in a prolonged period of immunodeficiency. Donor lymphocyte infusion (DLI) has been used to enhance graft-versus-leukemia activity after BMT, but the effects of DLI on immune reconstitution have not been established. We studied 9 patients with multiple myeloma who received myeloablative therapy and T-cell–depleted allogeneic BMT followed 6 months later by infusion of lymphocytes from the same donor. DLI consisted of 3 × 107 CD4+ donor T cells per kilogram obtained after in vitro depletion of CD8+ cells. Cell surface phenotype of peripheral lymphocytes, T-cell receptor (TCR) Vβ repertoire, TCR rearrangement excision circles (TRECs), and hematopoietic chimerism were studied in the first 6 months after BMT and for 1 year after DLI. These studies were also performed in 7 patients who received similar myeloablative therapy and BMT but without DLI. Phenotypic reconstitution of T and natural killer cells was similar in both groups, but patients who received CD4+ DLI developed increased numbers of CD20+ B cells. TCR Vβ repertoire complexity was decreased at 3 and 6 months after BMT but improved more rapidly in patients who received DLI (P = .01). CD4+ DLI was also associated with increased numbers of TRECs in CD3+ T cells (P < .001) and with conversion to complete donor hematopoiesis (P = .05). These results provide evidence that prophylactic infusion of CD4+ donor lymphocytes 6 months after BMT enhances reconstitution of donor T cells and conversion to donor hematopoiesis as well as promoting antitumor immunity.