Autologous stem cell transplant recipients tolerate haploidentical related-donor natural killer cell-enriched infusions.
BACKGROUND
In the setting of allogeneic stem cell transplantation (SCT), infusing natural killer (NK) cells from a major histocompatibility complex (MHC)-mismatched donor can mediate an antileukemic effect. The graft-versus-tumor effect after autologous stem cell transplantation (ASCT) may result in less disease relapse.


METHODS
We performed a Phase I clinical trial to assess the safety and feasibility of infusing distantly processed donor NK-enriched mononuclear cell (NK-MNC) infusions from a MHC haplotype-mismatched (haploidentical) donor to patients who recently underwent ASCT for a hematologic malignancy. On Day 1, peripheral blood MNCs were obtained by steady-state leukapheresis and sent from Boston to the Production Assistance for Cellular Therapies (PACT) facility at the University of Minnesota, where immunomagnetic depletion of CD3 cells was performed on Day 2. NK-MNC products were then returned to Boston on Day 2 for infusion on Day 3. Toxicity, cellular product characteristics, and logistic events were monitored.


RESULTS
At a median of 90 days (range, 49-191 days) after ASCT, 13 patients were treated with escalating doses of NK-MNCs per kilogram from 10(5)  to 2 × 10(7) . Adverse effects included Grade 2 rigors and muscle aches, but no Grade 3 or 4 events and no graft-versus-host disease or marrow suppression. One air courier delay occurred. NK-MNC products were viable with cytotoxic activity after transport.


CONCLUSIONS
CD3-depleted, MHC-mismatched allogeneic NK-MNC infusions can be safely and feasibly administered to patients after ASCT after distant processing and transport, justifying further development of this approach.
Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts 02111, USA. hklingemann@tuftsmedicalcenter.org
Hans
H
Klingemann
Carrie
C
Grodman
Elliott
E
Cutler
Marvin
M
Duque
Diane
D
Kadidlo
Andreas K
AK
Klein
Kellie A
KA
Sprague
Kenneth B
KB
Miller
Raymond L
RL
Comenzo
Tarun
T
Kewalramani
Neng
N
Yu
Richard A
RA
Van Etten
David H
DH
McKenna
D000328:Adult; D000368:Aged; D001782:Blood Donors; D005190:Family; D005240:Feasibility Studies; D005260:Female; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007262:Infusions, Intravenous; D007694:Killer Cells, Natural / Q000166:cytology / Q000637:transplantation*; D007937:Leukapheresis / Q000379:methods*; D008297:Male; D008875:Middle Aged; D014182:Transplantation, Autologous / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult