Clinical-grade purification of natural killer cells in haploidentical hematopoietic stem cell transplantation.
BACKGROUND
Because of a high risk of graft-versus-host disease (GVHD), donor lymphocyte infusions with unmodified lymphapheresis products are not used after haploidentical hematopoietic stem cell transplantation. Natural killer (NK) cells have antitumor activity and may consolidate engraftment without inducing GVHD. Production of NK cells under good manufacturing practice (GMP) conditions in a sufficient number is difficult.


METHODS
Twenty-four apheresis procedures and subsequent NK-cell enrichment from 14 haploidentical donors were performed. NK-cell enrichment was performed using a GMP suitable immunomagnetic procedure. Factors influencing the NK-cell recovery, purity, and NK-cell dose were analyzed.


RESULTS
A median number of 4.9 x 10(8) NK cells were obtained and median NK-cell recovery was 58 percent. Median T-cell depletion was 4.32 log. The absolute NK-cell number in the final product after processing significantly correlated with the preharvest NK-cell content of the peripheral blood (p = 0.002, r = 0.867). The NK-cell recovery was inversely correlated to the absolute NK-cell number in the apheresis product (p = 0.01, r = -0.51). The NK-cell dose per kg of body weight of the patient was inversely correlated to the weight of the patient (p = 0.007, r = -0.533).


CONCLUSIONS
Donors with a high NK-cell count in peripheral blood are likely to provide NK-cell products with the highest cell number. However, maximal NK-cell dose is limited and high NK-cell doses may only be obtained for patients with a low body weight, making children and young adults the best candidates for NK-cell therapy.
Meyer-Monard
Sandrine
S
Department of Biomedicine, University Hospital Basel, Switzerland. meyers@uhbs.ch
Passweg
Jakob
J
Siegler
Uwe
U
Kalberer
Christian
C
Koehl
Ulrike
U
Rovó
Alicia
A
Halter
Jörg
J
Stern
Martin
M
Heim
Dominik
D
Alois Gratwohl
Johannes Rischewski
JR
Tichelli
André
A
D001782:Blood Donors / Q000706:statistics & numerical data*; D002648:Child; D006085:Graft Survival / Q000276:immunology; D006239:Haplotypes / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D018189:Immunomagnetic Separation; D007694:Killer Cells, Natural / Q000276:immunology*; D007937:Leukapheresis / Q000379:methods / Q000706:statistics & numerical data; D008212:Lymphocyte Depletion; D017410:Practice Guidelines as Topic; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult