Preemptive Immunotherapy with Highly Purified CD56+/CD3− Natural Killer Cells after Haploidentical Stem Cell Transplantation. A Prospective Phase II Study in 2 Centers
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Media type:
E-Article
Title:
Preemptive Immunotherapy with Highly Purified CD56+/CD3− Natural Killer Cells after Haploidentical Stem Cell Transplantation. A Prospective Phase II Study in 2 Centers
Description:
<jats:title>Abstract</jats:title>
<jats:p>Allogeneic natural killer cells may exert cytotoxic activity against HLA-nonidentical tumor cells. This effect may be exploited after T-cell depleted haploidentical hematopoetic stem cell transplantation (HSCT) by using donor NK-cell infusions (NK-DLI) as adoptive immunotherapy.</jats:p>
<jats:p>In a prospective phase II study in 2 centers we treated 15 patients with NK-DLI preemptively with the goals to demonstrate feasibility and to explore whether such infusions would contribute to stabilize engraftment and exert graft versus leukemia activity without causing GvHD.</jats:p>
<jats:p>Patients were adults (6) or children (8) receiving transplants from haploidentical donors to treat AML (7) ALL (5) Hodgkin lymphoma (2) or sarcoma (1). Donors were haplotype mismatched siblings in 3 and parents in 12.</jats:p>
<jats:p>Donor NK cells were selected from unstimulated leukapheresis using immunomagnetic T cell depletion with anti-CD3 and NK cell enrichment with anti-CD56 coated microbeads on the CliniMACS ® device. Per protocol, patients in center A received NK-DLI on days +40 and +100 and in center B on days +3, +40 and +100. NK-DLI were either freshly infused or cryopreserved and thawed.</jats:p>
<jats:p>Center A Center B N 8 7 Adults / Children 6/2 0/7 Disease: AML/ALL/HD/oth 6/1/1/0 1/4/1/1 Number of NK-DLI per patient 1/2/3 2/5/1 2/3/2 Median NK-cell recovery (%) 62 37 NK-cell dose (10e7/kg) (median, range) 1.2 (0.5–3.4) 1.4 (0.66–3.23) T-cell dose (10e4/kg) (median, range) 0.2 (0–7.2) 0.23 (0–5.3) Events: graft failure / progression / GvHD (III–IV) 2/2/1 1/2/1 Alive / Dead 3/5 5/2 Cause of death: graft failure/progression/GvHD 2/2/1 0/2/0</jats:p>
<jats:p>NK-cell collection and ex vivo purification was successful in all donors. Outcome is shown in the Table. Of note: One patient in each center developed severe (grade III / grade IV) GvHD respectively. These 2 patients had received the highest T-cell dose. The remaining patients tolerated NK-DLI well and did not develop GvHD. Two patients in Center A experienced graft failure after NK-DLI in spite of NK-alloreactivity in GvHD direction.</jats:p>
<jats:p>In conclusion: highly purified NK cells may be infused in recipients of haploidentical HSCT recipients. None of the patients receiving &lt; 10e4/kg CD3+ cells developed GvHD. Further studies are needed to determine the optimal dose and timing of NK-DLI for anti-tumor activity in this setting.</jats:p>