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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-06-1929.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1891-1897
IMMUNOBIOLOGY
Evidence for naive T-cell repopulation despite thymus irradiation
after autologous transplantation in adults with multiple myeloma: role
of ex vivo CD34+ selection and age
Marion Malphettes,
Guislaine Carcelain,
Pierre Saint-Mezard,
Véronique Leblond,
Hester Korthals Altes,
Jean-Pierre Marolleau,
Patrice Debré,
Jean-Claude Brouet,
Jean-Paul Fermand, and
Brigitte Autran
From the Laboratoire d'Immunologie Cellulaire et
Tissulaire URA CNRS 625, Hôpital de la
Pitié-Salpêtrière, Paris, France; the
Service d'Immuno-Hématologie, Hôpital Saint-Louis, Paris,
France; and the Service d'Hématologie,
Hôpital de la Pitié-Salpêtrière, Paris,
France.
Immunodeficiency following autologous CD34+-purified
peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to
thymus irradiation. Aiming to assess the role of irradiated thymus in
T-cell repopulation, we studied 32 adults with multiple myeloma,
randomly assigned to receive high-dose therapy including total body
irradiation (TBI) followed by autologous transplantation with either
unselected or CD34+-selected PBSCs. The median number of
reinfused CD3+ cells was lower in the selected group (0.03 versus 14 × 106/kg; P = .002). Lymphocyte
subset counts were evaluated from month 3 to 24 after grafting. Naive
CD4+ T cells were characterized both by phenotype and by
quantification of T-cell receptor rearrangement excision circles
(TRECs). The reconstitution of CD3+ and CD4+ T
cells was significantly delayed in the CD34+-selected
group, but eventually led to counts similar to those found in the
unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+
subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells
appear to be CD62L . Age was identified as an independent
adverse factor for CD4+ and
CD62L+CD45RA+CD4+ T-cell
reconstitution. Our results provide evidence that infusing PBSCs
depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

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J.-H. Bourhis, Y. Bouko, S. Koscielny, M. Bakkus, H. Greinix, G. Derigs, G. Salles, W. Feremans, J. Apperley, D. Samson, et al.
Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study
Haematologica,
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[Abstract]
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