Poor lymphocyte recovery following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.
Positive selection of CD34+ cells in autologous grafts, designed to deplete tumour cells, also results in T-cell depletion. To assess the reconstitution of the different lymphocyte subsets and of the T-cell repertoire diversity following autologous transplantation of selected CD34+ peripheral blood stem cells (PBSC), we analysed sequential blood samples in eight patients autografted for advanced B-cell non-Hodgkin's lymphoma in a phase I-II pilot study. Although natural killer cell recovery was rapid, T- and B-cell recovery was delayed with a median of 110/microliters CD4+, 175/microliters CD8+ T cells and 45/microliters B cells at 12 months post-transplant. The naive CD45RA+ T-cell compartment was profoundly deficient up to 12 months for both CD4+ and CD8+ subsets. A transient expansion of memory CD8+CD45RO+ T cells consisting of an increased percentage of CD57+CD28- cells occurred within the first 3 months post-transplant, but the memory CD4+CD45RO+ T cells remained far below the normal value. The CD8+CD28+ T-cell subset did not recover. Using multiplex PCR analysis of the T-cell receptor gamma locus, we found that the repertoire diversity improved at 12 months after being poor and oligoclonal during the first 3 months post-transplant. As shown by monoplex PCRgamma analysis of every VJ combination, despite T-cell depletion of the graft, mature T cells were carried over with the selected CD34+ PBSC and contributed to the T-cell recovery after transplantation.
Diviné
M
M
Service d'Hématologie Clinique, Hôpital Henri Mondor, Créteil, France.
Boutolleau
D
D
Delfau-Larue
M H
MH
Beaujean
F
F
Jouault
H
H
Reyes
F
F
Kuentz
M
M
Bensussan
A
A
Farcet
J P
JP
Boumsell
L
L
D018952:Antigens, CD34; D016175:B-Lymphocyte Subsets; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000628:therapy*; D008231:Lymphopenia / Q000209:etiology; D008875:Middle Aged; D010865:Pilot Projects; D010976:Platelet Count; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018952:Antigens, CD34; D016692:Receptors, Antigen, T-Cell, gamma-delta