Table 4.
Impact of KIR on clinical outcomes in KIR haplotype and gene model.
| References | N | Disease | Donor | Graft manipulation | Clinical outcomes |
|---|---|---|---|---|---|
| Cooley et al. (40) | 448 | AML | URD | TCR | KIR B/x donor: higher RFS and cGVHD |
| Cook et al. (56) | 220 | Mixed | MSD | / | KIR2DS2: lower OS (HLA-C2C2 patients with myeloid diseases) |
| Verheyden et al. (57) | 65 | Mixed | MSD | TCD*, TCR | Donor co-presenting KIR2DS1 and 2DS2: lower relapse |
| Chen et al. (81) | 131 | Mixed | MSD | TCR | KIR2DS2: higher CMV reactivation (HLA-C2C2 patients); Additional activating KIR genes in donor: higher OS and lower CMV reactivation |
| Yabe et al. (45) | 1489 | Mixed | URD | TCD#, TCR | KIR2DS2: higher aGVHD3−4 (HLA-C mismatched transplants) |
| Schellekens et al. (82) | 83 | Mixed | MSD | TCR | KIR2DS1: higher OS (HLA-C1C1 patients); More activating KIRs in donor or patients: higher relapse; KIR2DS5 in patients or both in donor and patients: higher relapse |
| van der Meer et al. (83) | 70 | Mixed | MSD | TCD* | KIR2DS5: higher LFS and lower relapse (HLA-C1C1 or HLA-C2C2 patients); KIR2DS5: lower LFS and higher relapse (HLA-C1C2 patients) |
| Ludajic et al. (60) | 124 | Mixed | URD | TCD#, TCR | KIR2DS2: lower aGVHD2−4 (HLA-C1C2 patients) |
| Zaia et al. (84) | 211 | Mixed | MSD, URD | TCR | Donor co-presenting KIR 2DS2 and 2DS4: lower CMV reactivation; Donor aKIR gene content ≥5: lower CMV reactivation |
| Wu et al. (62) | 48 | Mixed | URD | TCD# | High aKIRs group: lower CMV reactivation rate |
| Gagne et al. (63) | 264 | Mixed | URD | TCR | KIR B/x donor: lower aGVHD3−4 (HLA identical pairs with myeloid disease) |
| Bao et al. (85) | 75 | Mixed | URD | TCD# | KIR B/x donor: higher OS |
| Venstrom et al. (86) | 1087 | Mixed | URD | TCD*, TCR | KIR3DS1: lower aGVHD2−4; KIR3DS1: lower aGVHD2−4, TRM and mortality (AML, CML and ALL) |
| Wu et al. (66) | 116 | Mixed | URD | TCD#, TCR | KIR2DS3: higher relapse, lower OS and DFS (myeloid cohort); More numbers of activating KIR genes in donor: higher relapse |
| Tomblyn et al. (87) | 116 | Mixed | URD | TCD*, TCR | KIR B/x donor: lower bacterial infections by day 180 |
| Cooley et al. (88) | 1409 | AML, ALL | URD | TCR | KIR B/x donor: lower relapse and higher DFS (AML); Cen-BB vs. Cen-BA or AA: lower relapse and higher DFS (AML); Tel-B/x vs. Tel-AA: lower relapse (AML); B content ≥ 2: lower relapse (AML) |
| Venstrom et al. (89) | 1277 | AML | URD | TCD*, TCR | Donor KIR2DS1 with HLA-C1/x patients vs. with HLA-C2C2 patients: lower relapse; KIR3DS1: higher OS |
| Zhou et al. (67) | 219 | Mixed | MSD | / | Cen-B/x donor: higher OS, RFS and lower relapse |
| Impola et al. (90) | 134 | Mixed | MSD | / | KIR 2DL2 or KIR 2DS2: better RFS (AML) |
| Bao et al. (91) | 210 | Mixed | URD | TCD# | KIR B/x donor: higher OS, RFS and lower NRM (AML and MDS); Cen-B/x donor: higher OS, RFS (AML and MDS at standard risk) |
| Cardozo et al. (70) | 50 | Mixed | MSD | TCR | KIR2DS2: lower OS and EFS |
| Bachanova et al. (92) | 614 | NHL | URD | TCD#, TCR | KIR B/x donor: lower relapse and better PFS (HLA matched transplants) |
| Kamenaric et al. (93) | 111 | Mixed | MSD, URD | TCD# | KIR2DS4 (neg vs. pos): no impact on GVHD (MSD) |
| Hosokai et al. (94) | 106 | Mixed | MSD, URD | TCR | KIR B/x donor: higher aGVHD3−4 (more evdient in HLA mismatched transplants) |
| Neuchel et al. (72) | 1446 | Mixed | URD | TCR | KIR2DS2: higher OS and DFS (HLA-C2C2 patients); KIR2DS1: lower relapse but higher TRM (HLA-C2C2 patients); KIR2DS5: lower relapse (HLA-C2C2 patients) |
| Gaafar et al. (74) | 87 | Mixed | MSD | TCR | KIR2DS2: HLA-C1 match: higher aGVHD2−4 (AML); KIR2DS1: HLA-C2 match: higher cGVHD (AML); Donor presenting KIR2DL1 or 2DS2: higher cGVHD (AML) |
| Sahin et al. (95) | 96 | AML, CML | MSD | TCR | KIR B/x donor: higher cGVHD |
| Heatley et al. (96). | 152 | Mixed | MSD | TCR | KIR2DS2: higher OS (AML); Cen-B/x donor: higher OS (AML) and lower aGVHD2−4 (AML); Tel B/x donor: lower CMV reactivation |
| Babor et al. (97) | 317 | Pediatric ALL | MSD, URD | TCD#, TCR | Higher ct-KIR score: lower relapse |
| Tordai et al. (98) | 314 | Mixed | MSD, URD | / | The combination of KIR2DS1 donor with HLA-C2 pos patients: higher OS |
| Nakamura et al. (99) | 288 | AML | MSD, URD | TCD*, TCD# | CMV reactivation: lower relapse and higher NRM (more evident in KIR B/x donor or when donor presenting KIR2DS1) |
| Bultitude et al. (100) | 119 | AML | URD | TCD, TCR | Cen-B/x donor: lower OS and NRM, higher IRM |
| Weisdorf et al. (101) | 2662 | AML | URD | TCD#, TCR | KIR B/x donor: lower relapse and higher LFS (RIC) |
| Verneris et al. (46) | 716 | Pediatric AL | URD | TCD#, TCR | KIR gene content: no significant impact on OS, DFS, relapse, TRM, or aGVHD |
| Zhao et al. (49) | 64 | Mixed | HRD | TCD# | KIR2DS3: higher aGVHD and cGVHD; KIR2DS5: higher aGVHD |
| Symons et al. (102) | 86 | Mixed | HRD | TCD# | KIR B/x donor: lower NRM and higher OS, EFS (KIR AA patients) |
| Chen et al. (76) | 84 | Mixed | HRD | TCD# | KIR2DS2: higher OS (lymphoid cohort); KIR2DS1: higher GVHD (lymphoid cohort) |
| Michaelis et al. (50) | 57 | Mixed | HRD | TCD* | KIR B/x donor: lower relapse |
| Zhao et al. (77) | 97 | CML | HRD | TCD# | KIR2DS3: lower EFS and OS, higher TRM; KIR2DS5: higher EFS and OS, lower TRM; KIR B/x donor: higher aGVHD3−4 |
| Oevermann et al. (103) | 85 | Pediatric ALL | HRD | TCD* | KIR B/x donor: lower relapse and better EFS; High donor KIR-B content: lower relapse and better EFS |
| Mancusi et al. (51) | 161 | AML, ALL | HRD | TCD* TCD*+Treg/Tcon |
Tel B/x vs. Tel AA: lower NRM and higher EFS (NK-alloreactive donors) KIR2DS1/3DS1: lower NRM and higher EFS (NK-alloreactive donors) KIR 2DS1 binding to HLA C2: increased inflammatory cytokine |
| Zhao et al. (53) | 180 | Mixed | HRD | TCD# | KIR2DS2: higher CMV reactivation |
| Solomon et al. (79) | 208 | Mixed | HRD | TCD# | KIR B/x donor with 2DS2 vs. KIR B/x donor without 2DS2: higher OS and DFS, lower relapse and NRM; KIR B/x donor with 2DS2 vs. KIR A/A donor: higher OS and DFS, lower NRM |
| Perez-Martinez et al. (104) | 192 | Pediatric mixed | HRD | TCD*, TCD# | KIR AA donor: higher relapse and lower DFS |
pos: positive; neg: negative; NHL, non-Hodgkin lymphoma; PFS, progression-free survival; NRM: non-relapse mortality.
TCD*: ex-vivo TCD; TCD#: in-vivo TCD.