Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases).
To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells.
Storek
Jan
J
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA 98109-1024, USA. jstorek@fhcrc.org
Zhao
Zhao
Z
Lin
Eugene
E
Berger
Thomas
T
McSweeney
Peter A
PA
Nash
Richard A
RA
Akatsuka
Yoshiki
Y
Metcalf
Monja D
MD
Lu
Hailing
H
Kalina
Tomas
T
Reindl
Markus
M
Storb
Rainer
R
Hansen
John A
JA
Sullivan
Keith M
KM
Kraft
George H
GH
Furst
Daniel E
DE
Maloney
David G
DG
D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology; D017690:Cell Transplantation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008231:Lymphopenia / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014777:Virus Diseases / Q000150:complications / Q000276:immunology
D000906:Antibodies; D018952:Antigens, CD34