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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3505-3512
PLENARY PAPER
Immunity of patients surviving 20 to 30 years after allogeneic or
syngeneic bone marrow transplantation
Jan Storek,
Ansamma Joseph,
German Espino,
Monja A. Dawson,
Daniel C. Douek,
Keith M. Sullivan,
Mary E. D. Flowers,
Paul Martin,
George Mathioudakis,
Richard A. Nash,
Rainer Storb,
Frederick R. Appelbaum, and
David G. Maloney
From the Fred Hutchinson Cancer Research Center and
University of Washington, Seattle, WA; and Vaccine Research Center,
National Institute of Allergy and Infectious Diseases, and Department
of Experimental Transplantation and Immunology, Medicine Branch,
National Cancer Institute, National Institutes of Health, Bethesda, MD.
The duration of immunodeficiency following marrow transplantation
is not known. Questionnaires were used to study the infection rates in
72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who
originally donated the marrow) leukocyte subsets were assessed by flow
cytometry. T-cell receptor excision circles (TRECs), markers of T cells
generated de novo, were quantitated by real-time polymerase chain
reaction. Immunoglobulin G2 (IgG2) and
antigen-specific IgG levels were determined by enzyme-linked
immunosorbent assay. Infections diagnosed 15 years after
transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding
respiratory tract infections, gastroenteritis, lip sores, and hepatitis
C. The counts of circulating monocytes, natural killer cells, B cells,
CD4 T cells, and CD8 T cells in the patients were not lower than in the
donors. The counts of TREC+ CD4 T cells in transplant
recipients younger than age 18 years (at the time of transplantation)
were not different from the counts in their donors. In contrast, the
counts of TREC+ CD4 T cells were lower in transplant
recipients age 18 years or older, even in those with no history of
clinical extensive chronic graft-versus-host disease, compared with
their donors. The levels of total IgG2 and specific IgG
against Haemophilus influenzae and Streptococcus
pneumoniae were similar in patients and donors. Overall, the
immunity of patients surviving 20 to 30 years after
transplantation is normal or near normal. Patients who received
transplants in adulthood have a clinically insignificant deficiency of
de novo-generated CD4 T cells, suggesting that in these patients the
posttransplantation thymic insufficiency may not be fully reversible.
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