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Blood, 15 June 2002, Vol. 99, No. 12, pp. 4610-4617
TRANSPLANTATION
Immunologic effects of prophylactic donor lymphocyte infusion
after allogeneic marrow transplantation for multiple myeloma
Roberto Bellucci,
Edwin P. Alyea,
Edie Weller,
Antoinette Chillemi,
Ephraim Hochberg,
Catherine J. Wu,
Christine Canning,
Robert Schlossman,
Robert J. Soiffer,
Kenneth C. Anderson, and
Jerome Ritz
From the Center for Hematologic Oncology and Department
of Biostatistics, Dana-Farber Cancer Institute; Department of Medicine,
Brigham and Women's Hospital; and Harvard Medical School; all of
Boston, MA.
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) V
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 V
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.
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