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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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2002-06-1929v1
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Submitted June 28, 2002
Accepted October 5, 2002

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, Veronique Leblond, Hester Korthals Altes, Jean-Pierre Marolleau, Patrice Debre, Jean-Claude Brouet, Jean-Paul Fermand, and Brigitte Autran*

Laboratoire d'Immunologie Cellulaire et Tissulaire URA CNRS 625, Hopital de La Pitie-Salpetriere, Paris, France
Service d'Immuno-Hematologie, Hopital Saint-Louis, Paris, France
Service d'Hematologie, Hopital de La Pitie-Salpetriere, Paris, France

* Corresponding author; email: brigitte.autran{at}psl.ap-hop-paris.fr.

Immunodeficiency following autologous CD34+ purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft and/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 PBSC. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 106/kg; p=0.002). Lymphocyte subset counts were evaluated from Month 3 to 24 post-graft. Naive CD4+ T-cells were characterized both by phenotype and by T-cell receptor rearrangement excision circles (TRECs) quantification. The reconstitution of CD3+ and CD4+ T-cells was significantly delayed in the CD34+ selected group, but eventually led to similar counts than 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 CD45RA+CD4+ T-cells appear to be CD62L-negative. Age was identified as an independent adverse factor for CD4+ and CD62L+ CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing T-cell depleted PBSCs 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, August 1, 2007; 92(8): 1083 - 1090.
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