Table 3.
Impact of therapeutic use of NK and CIK cell infusions on outcomes after allogeneic HSCT.
| Author/Year | Shaffer et al., 2015 | Lee et al., 2016 | Introna et al., 2007 | Laport et al., 2011 | Linn et al., 2012 |
|---|---|---|---|---|---|
| Study type | Clinical Trial Phase 2, NK cells | Clinical Trial Phase 1 | Clinical Trial Phase 1, CIK cells | Clinical Trial Phase 1, CIK cells | Clinical Trial Phase 1-2, CIK cells |
| Patients, n | 8 | 21 | 11 | 18 | 16 |
| Age (years), Median (range) | 19 (1.9-55.9) | 51 (2-63) | 53 (24-62) | 53 (20-69) | 36 (20-60) |
| Male, n (%) | NA | 15 (71) | 5 (45.4) | NA | 7 (44) |
| Diagnosis, n (%) | AML: 6 (75), MDS: 2 (25) | AML: 8 (38), CML: 7 (30), MDS: 6 (28.5) | AML: 4 (36), HD: 3 (27), CML: 1 (9), ALL: 1(9), MDS: 2 (18) | NHL: 5 (27), AML: 3 (16), MM: 3 (16), CLL: 2 (10), ALL: 2 (10), MDS: 2 (10), HL: 1 (5) | ALL: 3 (18), HD: 3 (18), AML: 8 (50), CML: 1 (6), NHL: 1 (6) |
| Disease status | Relapsed or persistent disease | Relapsed or persistent disease | Relapsed disease | Relapsed disease | Relapsed disease |
| HSCT donor | MSD: 7 (87.5); MUD: 1(12.5) | MSD 13 (72%); MUD 8 (38%) | MSD: 6 (54); MUD: 5 (45) | MSD: 18 (100) | Haplo: 12 (75); MUD: 3 (19); UCB: 1(6) |
| NK/CIK cell donor | Haplo: 8 (100). Third party | Haplo: 21 (100), third party | Autologous CIK cells: 11 (100) | MSD: 18 (100). Same matched sibling donor | HSCT donors: 20; Autologous: 5 a |
| Product Manipulation | PBMCs collected by apheresis, CD3+ T-cell depletion with CliniMACS, followed by CD56+ selection | PBMCs collected by apheresis, CD3+ T-cell depletion with CliniMACS (first 3 patients received CD56+ selection), culture with IL-2; post-infusion IL-2 | Leukapheresis product was expanded using CIK cells expansion cultures, using IFN-γ, CD3 antibody, and IL-2 | Leukapheresis product was expanded using CIK cells expansion cultures, using IFN-γ, CD3 antibody, and IL-2 | Leukapheresis product was expanded using CIK cells expansion cultures, using IFN-γ, CD3 antibody, and IL-2 |
| Number of infusions | 1 | 4 | Repeated infusions at 3–4-week intervals; Median number of CIK infusions were 2 | 1 | 55 (1–12 infusions per patient); at a minimum of 4-week intervals |
| NK cell infusion dose/kg, (range) | 10.6 (4.3 - 22.4) x 106 | Escalating dosage: 1 x 106; 5 x 106; 3 x 107; 3 x 107 | 12.4 (7.2 - 87.4) x 106 | Escalating dose: 1 x 107; 5 x 107; 1 x 108 | 10-200 x 106 |
| Pre-NK cell Conditioning | Flu/Cy with IL-2 | RIC (BuFluATG) 21 (100) | None. Other therapies included DLI 3, Chemotherapy 2, DLI plus Chemo 3, RT 1 | None | None. Treated with investigator’s choice therapy concurrently |
| CR, n (%) | 2 (25) | 11 (78.5) | 3 (27.2) | 2 (11.1) | NA |
| ORR, n (%) | 3 (37.5) | 21 (100) | 3 (27.2) | 14 (77.7) | 5 (31.2) |
| OS, n (%) | NA | 5 (23%) – 7.6 months | 4 (36.3%); Median OS 2.5 (2.1-2.7) years | 10 (55.5%) at 2.3 years; Median OS 28 months | NA b |
| Follow up (months), median (range) | NA | NA | 20.5 | 20 (1-69) | 4 |
| Relapse, n (%) | 3 (37.5) | 12 (57.1) | NA | 16 (88.8) | 9 (56.2) |
| Acute GVHD, n (%) | 0 | 10 (47.6) | 4 (36.3) | 2 (11.1) | 3 (18.7) |
| Chronic GVHD, n (%) | 0 | 6 (30) | 2 (18.1) | 1 (5.5) | 2 (12.5) |
Donor cells may be mobilized peripheral blood stem cells (cryopreserved), leukapheresis product or harvested from patient if donor not available
Individual patient level data available, cumulative data not available.
HSCT, hematopoietic stem cell transplant; CR, complete remission; ORR, Overall response rate; NA, Not available; AML, Acute myeloid leukemia; ALL, Acute lymphoblastic leukemia; HD, Hodgkin’s lymphoma; SCA, Sarcoma; MDS,Myelodysplastic syndrome; NHL, Non-Hodgkin’s lymphoma; CML, Chronic myeloid leukemia; CMML, Chronic myelomonocytic leukemia; MM, Multiple myeloma; CLL, Chronic lymphocytic leukemia; UCB – Umbilical Cord Blood; Haplo, Haploidentical; MSD, Matched sibling donor: MUD, Matched unrelated donor; MAC, Myeloablative conditioning: TCD, T cell depleted; RIC, reduced intensity conditioning; BuFluATG, Busulfan, fludarabine, thymoglobulin; PT-Cy, Post-transplant cyclophosphamide; FluCy, Fludarabine, cyclophosphamide; CIK cells, Cytokine-induced killer cells; PBMCs, peripheral blood mononuclear cells; IFN-γ, Interferon-gamma; IL, Interleukin