Purification of CD4+ T cells for adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation.
Donor lymphocyte infusions (DLIs) are used for adoptive immunotherapy to prevent or treat relapse and infectious complications after allogeneic hematopoietic stem cell transplantation (HSCT). Unmanipulated DLIs are associated with a risk of graft-versus-host disease (GVHD), probably related to CD8(+) T cell activity. We investigated an automated clinical-scale human-CD4(+)-cell purification method to deplete CD8(+) cells. Twenty-four stem cell recipients received a total of 24 leukapheresis products being enriched for CD4(+) cells using magnetic associated cell sorting (MACS) with an automated device (CliniMACS(®)) before DLIs. MACS resulted in a mean CD4(+) cell count of 16 × 10(6)/kg bw corresponding to 3.4-fold CD4(+) cell enrichment. Mean yield and purity of CD45(+)CD3(+)CD4(+)CD14(-)7AAD(-) were 74% ± 23% and 82% ± 11%, respectively. Median initial dose of DLIs was 1.1 × 10(6) CD4(+)/kg. During a median follow-up of 25 months, 7 (30%) patients experienced GVHD (acute II-IV: n = 4, 17%; acute III-IV: n = 2, 8%; chronic limited: n = 2, 8%; chronic extensive: n = 1, 4%). Thirteen of 21 further evaluable patients (62%) showed measurable clinical response, 2 patients with therapy refractory infectious complications (HSV) showed remarkable immunologic improvement. Automated enrichment of CD4(+) by magnetic cell sorting provides an efficient and rapid method for processing donor lymphocytes. Additional studies should further investigate this approach in terms of efficacy and the risk of GVHD.
Klyuchnikov
Evgeny
E
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sputtek
Andreas
A
Slesarchuk
Olga
O
Lioznov
Michael
M
Stübig
Thomas
T
Bacher
Ulrike
U
Amtsfeld
Gitta
G
Merle
Edeltraut
E
Reckhaus
Marie-Luise
ML
Fehse
Boris
B
Wolschke
Christine
C
Adjallé
Raissa
R
Ayuk
Francis
F
Zander
Axel
A
Kröger
Nicolaus
N
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D018189:Immunomagnetic Separation / Q000295:instrumentation / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D009894:Opportunistic Infections / Q000517:prevention & control / Q000628:therapy; D012189:Retrospective Studies; D055502:Secondary Prevention; D016019:Survival Analysis; D055815:Young Adult