Table 4.
Impact of pre-emptive/prophylactic NK cells infusions on outcomes after haploidentical HSCT.
| Author/Year | Stern et al., 2013 | Choi et al., 2014 | Ciuera et al., 2017 | Passweg et al., 2004 |
|---|---|---|---|---|
| Study type | Clinical Trial Phase 2 | Clinical Trial Phase 1 | Clinical Trial Phase 1 | Pilot Study |
| Patients, n | 16 | 41 | 13 | 5 |
| Age (years), Median (range) | A: 23 (8-32), B: 10 (8-23) | 47 (17-75) | 44 (18-60) | 16 (3-25) |
| Male, n (%) | NA | 23 (56) | 6 (46) | 2 (40) |
| Diagnosis, n (%) | AML: 8 (50), ALL: 5 (31), HL: 2 (12.5), SCA: 1 (6) | ALL: 7 (17), AML: 32 (78), MDS: 1 (2), NHL: 1 (2) | AML: 8 (61.5), CML: 5 (38), MDS: 1 (7.7) | AML: 4 (80), CML: 1 (20) |
| Diagnosis specification | Haplo HSCT | Haplo HSCT | High risk myeloid malignancies | NK-DLI in case of poor engraftment or relapse |
| HSCT donor | Haplo: 16 (100) | Haplo: 41 (100) | Haplo: 13 (100) | Haplo: 5 (100) |
| NK cell donor | Same as HSCT donor | Same as HSCT donor | Same as HSCT donor | Same as HSCT donor |
| 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 or RosetteSep system. Cultured with IL-15, IL-21 and hydrocortisone | PBMCs collected by apheresis, CD3+ T-cell depletion with CliniMACS. Ex vivo expansion using K562 feeder cells expressing membrane-bound IL-21 | PBMCs collected by apheresis, CD3+ T-cell depletion with CliniMACS, followed by CD56+ selection |
| Timing of infusion | Center A: Day +40, +100 Center B: Day +3, +40, +100 |
First infusion 2 weeks after HCT, second infusion 3 weeks after HCT | Day +2, +7, +28 | NK-DLI in case of poor engraftment (n = 3), graft failure (n = 1), and early relapse (n = 1) |
| Number of infusions | 29 total, 1.8 per patient | 2 | 3 | 2 |
| NK cell infusion dose/kg, (range) | 1.21 (0.3-3.8) x107 | Escalating dosage: 0.2 x 108; 0.5 x 108; 1.0 x 108; ≥1.0 x 108 | 1 x 105 – 1 x 108 | 1.61 (0.21-2.2) x 107 |
| HSCT Conditioning | MAC/TCD 16 (100) | RIC (BuFluATG) 41 (100) | Mel based RIC with PT-Cy: 13 (100) | MAC/TCD: 5 (100) |
| CR, n (%) | 2 (12.5) | AML: 21 (72); ALL/NHL: 4 (50) | NA | 3 (60) |
| ORR, n (%) | 13 (81.3) | NA | NA | 3 (60) |
| OS, n (%) | 44 ± 12% at 1 yr: 25 ± 11% - 2 & 5 yrs |
AML: 31% -4 yrs; ALL/NHL:0 -1 yrs |
11 (85%) – 1 yr | 4 (80%)- 1 yr |
| Follow up (months), median (range) | 69.6 (63.6-81.6) | 31.5 (16-53) | 14.7 (8-25.1) | 12 (8-18) |
| Relapse, n (%) | 7 (43.8) | 15 (37) | 1 (7.7) | 1(20) |
| Acute GVHD, n (%) | 4 (25) | 9 (22) | 7 (54) | 0 |
| Chronic GVHD, n (%) | 0 | 10 (24) | 0 | 0 |
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; Haplo, Haploidentical; MAC, Myeloablative conditioning: TCD, T cell depleted; RIC, reduced intensity conditioning; BuFluATG, Busulfan, fludarabine, thymoglobulin; PT-Cy, Post-transplant cyclophosphamide; FluCy, Fludarabine, cyclophosphamide; Mel, Melphalan; PBMCs, peripheral blood mononuclear cells; DLI, donor lymphocyte infusion; IL, Interleukin.