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Relationship between patterns of engraftment in peripheral blood and immune
reconstitution after allogeneic bone marrow transplantation for (severe)
combined immunodeficiency
JE van Leeuwen, MJ van Tol, AM Joosten, PT Schellekens, RL van den Bergh, JL Waaijer, NJ Oudeman-Gruber, CP van der Weijden-Ragas, MT Roos and EJ Gerritsen
Department of Pediatrics, Leiden University Hospital, The Netherlands.
We report the outcome of allogeneic bone marrow transplantation (BMT) as
treatment for severe combined immunodeficiency disease (SCID) in 31
patients grafted from 1968 until 1992. The patients received a graft from
an HLA-identical related (n = 10), an HLA-haplo-identical related (n = 19),
or a closely HLA-matched unrelated (n = 2) donor that resulted in the
long-term survival of 6 of 10, 9 of 19, and 0 of 2 children, respectively.
Major complications included failure of engraftment and early death caused
by respiratory failure. The chimerism pattern and immunologic
reconstitution were evaluated in 15 children who survived more than 1 year
with sustained engraftment. The pattern of engraftment was investigated
within flow-sorted peripheral blood (PB) T- and B-lymphoid, natural killer
(NK), and myelomonocytic cell populations using the amplification of
variable number of tandem repeats by the polymerase chain reaction. The
immunologic reconstitution was assessed by various in vitro and in vivo
parameters. Although the number of PB T cells and the in vitro T-cell
proliferative response was in the lower region of normal in the majority of
cases and even subnormal in some, in all cases donor T-cell engraftment and
reconstitution of T-cell immunity was observed. Residual host-type T cells
(1% to 5%) were detected in eight cases at multiple occasions. All children
showed normal serum IgM and IgG subclass levels and produced specific IgG
antibodies after vaccination, irrespective of donor B-cell engraftment.
However, three HLA haplo-identical graft recipients with host-type B
lymphoid and myeloid cells have a persistent selective IgA deficiency. NK
cells were either of donor, host, or mixed origin. Donor NK cell
engraftment restored defective in vitro NK cell function of the recipient.
We conclude that determination of lineage-specific engraftment patterns
provides valuable information for the understanding of the immunologic
reconstitution after allogeneic BMT for SCID.
Volume 84,
Issue 11,
pp. 3936-3947,
12/01/1994
Copyright © 1994 by The American Society of Hematology
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