al., et

Fehniger, Todd A.

Weisdorf, Daniel

English

Digital Commons@Becker

  1 KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation   Supplemental Tables 1-3     2 Supplemental Table 1. Previous vs. Current Cohort.  Demographics and Outcomes JI Cohort 1988-2009 Current Cohort 2010-2016 Conditioning Intensity MAC (100%)* N = 1532           RIC (40%)  N = 1083                 MAC (60%)**  N = 1579                  Recipient Age (median) % over age 60 38 3% 64 71% 49 18% Male (%) 55% 49% 52% HLA allele match    8/8 (%)    7/8 (%)    >1 allele mismatch (%)  92% 7% 1%  87% 13% 0%  84% 16% >1% Poor Risk Cytogenetics 25% 19% 19% KPS <90 32% 45% 30% Graft Source: PBSC (%) 47% 92% 81% Donor Age (median) 34 28 29 Advanced Disease status (%) 32% 1% 2% Recipient CMV Seropositive (%) 54% 65% 67% GVHD Prophylaxis TAC +/- others (%) CSA +/- others (%)  51% 46%  83% 17%  92% 8% KIR B/x Donors (%) 67% 69% 69% Follow-up of Survivors Median (range) months 60 (3-240) 38 (6-99) 44 (2-98) Outcomes    Overall Survival at 5 years (95% CI) 32 (30-34) 39 (36-43) 49 (46-52) DFS at 5 years (95% CI) 29 (26-31) 35 (32-39) 46 (43-38) Relapse at 3 years (95% CI) 34 (32-37) 34 (31-36) 29 (27-31) NRM at 1 year (95% CI) 27 (25-29) 16 (14-18) 15 (13-16) Donor KIR Bx association with  outcomes in C1/x recipients HR KIR Bx vs. AA* HR KIR Bx vs. AA HR KIR Bx vs. AA**   3 *from Cooley, et al. (10) **in current MAC recipients no influence of KIR genotype was seen, in C1/x or others. Relapse 0.70 (0.56-0.87) P=0.0018 0.78  (0.62-0.98) P=0.037 0.96 (0.78,1.19) P=0.73  DFS 0.78 (0.67-0.91) P=0.0015 0.85  (0.72-0.99) P=0.04 1.07 (0.89,1.29) P=0.46    4 Supplemental Table 2. Multivariate Analysis  2A.  Reduced Intensity Conditioning   2B.  Myeloablative Conditioning Overall Survival   Overall Survival Factor N Event HR HR Low HR Upper P   Factor N Event HR HR Low HR Upper P Donor KIR haplotype . . . . . *0.069   Donor KIR haplotype . . . . . *0.61 AA 336 197 1.00 . . .   AA 491 229 1.00 . . . BX 730 388 0.85 0.71 1.01 0.069   BX 1066 504 1.05 0.88 1.24 0.61 HLA matched alleles . . . . . 0.0056   HLA matched alleles . . . . . 0.0007 7/8 146 100 1.00 . . .   7/8 245 134 1.00 . . . 8/8 920 485 0.69 0.53 0.90 0.0056   8/8 1312 599 0.71 0.58 0.87 0.0007 Cytogenetics . . . . . *0.050   Cytogenetics . . . . . *0.0023 Disease status . . . . . *0.030   Disease status . . . . . *<.0001 Early 838 447 1.00 . . .   Early 1152 529 1.00 . . . Intermediate 219 130 1.19 0.98 1.44 0.079   Intermediate 373 181 1.17 0.99 1.38 0.058 Advanced 9 8 2.72 1.13 6.54 0.025   Advanced 32 23 2.52 1.71 3.71 <.0001 Recipient age . . . . . 0.089   Recipient age . . . . . 0.0014 Recipient CMV status . . . . . 0.052    Recipient CMV status . . . . . 0.14 GVHD prophylaxis . . . . . *0.037  GVHD prophylaxis      *<.0001 ATG/ alemtuzumab . . . . . 0.84  ATG/ alemtuzumab . . . . . 0.044 No ATG/ alemtuzumab 619 334 1.00 . . .  No ATG/ alemtuzumab 936 443 1.00 . . . ATG alone 404 225 1.03 0.83 1.29 0.75  ATG alone 590 275 1.01 0.85 1.18 0.95 alemtuzumab alone 43 26 1.13 0.70 1.83 0.62  alemtuzumab alone 31 15 0.44 0.23 1.85 0.015 HLA-DP mismatch . . . . . 0.49  HLA-DP mismatch . . . . . 0.52 Fully matched 178 109 1.00 . . .  Fully matched 265 141 1.00 . . . Mismatch 874 307 1.12 0.89 1.41 0.34  Mismatch 1270 593 0.97 0.80 1.18 0.77   5 Missing  13 9 1.29 0.63 2.65 0.49  Missing  19 10 0.96 0.47 1.96 0.91  Factor N Event HR HR Low HR Upper P   Factor N Event HR HR Low HR Upper P Donor KIR centromeric regions . . . . . 0.20   Donor KIR centromeric regions . . . . . 0.96 AA 485 279 1.00 . . .   AA 747 358 1.00 . . . AB 483 259 0.87 0.73 1.03 0.1030   AB 647 300 0.99 0.83 1.19 0.9481 BB 98 47 0.80 0.58 1.10 0.1613   BB 163 75 1.03 0.82 1.29 0.8126 HLA matched alleles . . . . . 0.0085   HLA matched alleles . . . . . 0.0007 7/8 146 100 1.00 . . .   7/8 245 134 1.00 . . . 8/8 920 485 0.70 0.53 0.91 0.0085   8/8 1312 599 0.71 0.58 0.87 0.0007 Cytogenetics . . . . . 0.046   Cytogenetics . . . . . 0.0022 Disease status . . . . . *0.027   Disease status . . . . . *<.0001 Early 838 447 1.00 . . .   Early 1152 529 1.00 . . . Intermediate 219 130 1.20 0.99 1.45 0.0633   Intermediate 373 181 1.17 0.99 1.38 0.0627 Advanced 9 8 2.72 1.12 6.63 0.0273   Advanced 32 23 2.54 1.72 3.75 0.0000 Recipient age . . . . . 0.11   Recipient age . . . . . *0.0013 Recipient CMV status . . . . . 0.071   Recipient CMV status . . . . . 0.14 GVHD prophylaxis . . . . . *0.036  GVHD prophylaxis . . . . . *<.0001 ATG/ alemtuzumab . . . . . 0.82  ATG/ alemtuzumab . . . . . *0.038 No ATG/ alemtuzumab 619 334 1.00 . . .  No ATG/ alemtuzumab 936 443 1.00 . . . ATG alone 404 225 1.03 0.83 1.27 0.82  ATG alone 590 275 1.01 0.86 1.18 0.92 alemtuzumab alone 43 26 1.15 0.72 1.84 0.56  alemtuzumab alone 31 15 0.44 0.23 0.84 0.0023 HLA-DP Mismatch . . . . . 0.47  HLA-DP mismatch . . . . . 0.96 Fully matched 178 109 1.00 . . .  Fully matched 268 141 1.00 . . . Mismatch 874 307 1.12 0.89 1.40 0.34  Mismatch 1270 593 0.97 0.80 1.18 0.79 Missing  13 9 1.31 0.65 2.61 0.45  Missing  19 10 0.96 0.47 1.96 0.91 Stratified variables: Karnofsky Performance score   Stratified variables: Karnofsky Performance score  Adjusted multivariate analysis for the endpoints shown stratified as indicated.             6 *Represents overall p value for the variable group;  Bolded p values are independently significant p<0.05     7 Supplemental Table 3 Individual Donor KIR B Genes: Influence on Outcome.   Table 3A.  Donor KIR B genes and Relapse, DFS and Surviva                      RIC  MAC Relapse      Relapse                Donor KIR Group N RR 95% CI P  Donor KIR Group N RR 95% CI P KIR A/A  334 1    KIR A/A  490 1   KIR B/x with 2DS1+ 381 0.75 (0.60-0.95) 0.016  KIR B/x with 2DS1+ 601 0.96  (0.77-1.21) 0.74 KIR B/x with 2DS2+ 558 0.73  (0.57-0.93) 0.010  KIR B/x with 2DS2+ 780 0.94  (0.77-1.14) 0.51 KIR B/x with 2DS3+ 287 0.61  (0.47-0.79) 0.0001  KIR B/x with 2DS3+ 412 1.00  (0.78-1.28) 0.99 KIR B/x with 2DS5+ 292 0.77 (0.61-0.98) 0.037  KIR B/x with 2DS5+ 485 1.00 (0.80-1.24) 0.97 KIR B/x with 2DL2+ 554 0.72  (0.56-0.93) 0.010  KIR B/x with 2DL2+ 775 0.93  (0.77-1.13) 0.48 KIR B/x with 2DL5+ 489 0.70  (0.56-0.87) 0.0016  KIR B/x with 2DL5+ 757 0.97  (0.79-1.19) 0.76 KIR B/x with 3DS1+ 369 0.75  (0.60-0.95) 0.016  KIR B/x with 3DS1+ 589 1.03  (0.83-1.28) 0.77            DFS      DFS                Donor KIR Group N RR 95% CI P  Donor KIR Group N RR 95% CI P KIR A/A  334 1    KIR A/A  489 1   KIR B/x with 2DS1+ 381 0.87 (0.73-1.03) 0.10  KIR B/x with 2DS1+ 600 1.06 (0.90-1.26) 0.47 KIR B/x with 2DS2+ 557 0.80  (0.66-0.97) 0.020  KIR B/x with 2DS2+ 778 1.07  (0.90-1.26) 0.44 KIR B/x with 2DS3+ 287 0.76  (0.62-0.92) 0.0054  KIR B/x with 2DS3+ 412 1.09 (0.89-1.33) 0.42 KIR B/x with 2DS5+ 292 0.86 (0.72-1.03) 0.10  KIR B/x with 2DS5+ 484 1.05 (0.89-1.24) 0.58 KIR B/x with 2DL2+ 554 0.80  (0.66-0.97) 0.025  KIR B/x with 2DL2+ 773 1.08 (0.91-1.27) 0.39 KIR B/x with 2DL5+ 489 0.83  (0.69-0.99) 0.037  KIR B/x with 2DL5+ 756 1.07 (0.91-1.25) 0.40 KIR B/x with 3DS1+ 369 0.85 (0.71-1.01) 0.066  KIR B/x with 3DS1+ 588 1.11  (0.94-1.31) 0.20 Supplemental Table 3 A.          RIC   MAC Survival      Survival       8            Donor KIR Group N RR 95% CI P  Donor KIR Group N RR 95% CI P KIR A/A 336 1    KIR A/A 491 1   KIR B/x with 2DS1+ 381 0.91 (0.75-1.10) 0.31  KIR B/x with 2DS1+ 605 1.02 (0.86-1.22) 0.80 KIR B/x with 2DS2+ 557 0.82 (0.67-1.00) 0.055  KIR B/x with 2DS2+ 784 1.05 (0.88-1.26) 0.58 KIR B/x with 2DS3+ 287 0.81 (0.65-1.01) 0.056  KIR B/x with 2DS3+ 414 1.03 (0.83-1.28) 0.78 KIR B/x with 2DS5+ 292 0.88 (0.72-1.09) 0.24  KIR B/x with 2DS5+ 488 1.02 (0.84-1.23) 0.85 KIR B/x with 2DL2+ 554 0.82 (0.67-1.01) 0.058  KIR B/x with 2DL2+ 779 1.06 (0.88-1.28) 0.52 KIR B/x with 2DL5+ 489 0.86 (0.71-1.05) 0.13  KIR B/x with 2DL5+ 762 1.03 (0.87-1.22) 0.75 KIR B/x with 3DS1+ 369 0.89 (0.73-1.08) 0.24  KIR B/x with 3DS1+ 594 1.06 (0.89-1.27) 0.51 Bolded p values are independently significant p<0.05/7=0.007   Table 3B. Donor KIR B genes in Recipients with C1/x and Outcome  RIC with Recipient C1/x MAC with Recipient C1/x Relapse      Relapse                Donor KIR Group N RR 95% CI P  Donor KIR Group N RR 95% CI P KIR A/A  302 1    KIR A/A  405 1   KIR B/x with 2DS1+ 329 0.72  (0.56-0.94) 0.014  KIR B/x with 2DS1+ 512 0.94  (0.73-1.23) 0.66 KIR B/x with 2DS2+ 486 0.74  (0.57-0.95) 0.020  KIR B/x with 2DS2+ 665 0.95  (0.76-1.19) 0.64 KIR B/x with 2DS3+ 240 0.60  (0.45-0.78) 0.0002  KIR B/x with 2DS3+ 357 0.93 (0.68-1.25) 0.62 KIR B/x with 2DS5+ 250 0.76  (0.58-0.99) 0.043  KIR B/x with 2DS5+ 413 1.01 (0.77-1.31) 0.95 KIR B/x with 2DL2+ 482 0.73  (0.57-0.95) 0.020  KIR B/x with 2DL2+ 662 0.95 (0.75-1.18) 0.63 KIR B/x with 2DL5+ 418 0.70  (0.56-0.88) 0.0021  KIR B/x with 2DL5+ 646 0.93 (0.73-1.20) 0.59 KIR B/x with 3DS1+ 317 0.74  (0.57-0.95) 0.018  KIR B/x with 3DS1+ 502 1.00  (0.77-1.29) 0.99            DFS      DFS                Donor KIR Group N RR 95% CI P  Donor KIR Group N RR 95% CI P KIR A/A  302 1    KIR A/A  404 1     9 KIR B/x with 2DS1+ 329 0.87 (0.73-1.03) 0.11  KIR B/x with 2DS1+ 511 1.04 (0.84-1.27) 0.73 KIR B/x with 2DS2+ 486 0.80 (0.66-0.97) 0.027  KIR B/x with 2DS2+ 663 1.08 (0.89-1.32) 0.43 KIR B/x with 2DS3+ 240 0.75  (0.60-0.93) 0.0081  KIR B/x with 2DS3+ 357 1.06  (0.83-1.35) 0.64 KIR B/x with 2DS5+ 250 0.88 (0.73-1.07) 0.20  KIR B/x with 2DS5+ 412 1.05 (0.86-1.30) 0.62 KIR B/x with 2DL2+ 482 0.80  (0.66-0.98) 0.031  KIR B/x with 2DL2+ 660 1.09 (0.90-1.33) 0.38 KIR B/x with 2DL5+ 418 0.84 (0.70-1.01) 0.057  KIR B/x with 2DL5+ 645 1.05 (0.87-1.28) 0.62 KIR B/x with 3DS1+ 317 0.86 (0.72-1.02) 0.085  KIR B/x with 3DS1+ 501 1.07  (0.88-1.32) 0.50       Survival      Survival                Donor KIR Group N RR 95% CI P  Donor KIR Group N RR 95% CI P KIR A/A 304 1    KIR A/A 406  1  KIR B/x with 2DS1+ 329 0.88 (0.72-1.06) 0.18  KIR B/x with 2DS1+ 515 1.02 (0.82-1.26) 0.86 KIR B/x with 2DS2+ 486 0.80 (0.65-0.98) 0.029  KIR B/x with 2DS2+ 667 1.08 (0.88-1.32) 0.47 KIR B/x with 2DS3+ 240 0.75 (0.59-0.96) 0.022  KIR B/x with 2DS3+ 357 1.03 (0.80-1.32) 0.83 KIR B/x with 2DS5+ 250 0.87 (0.70-1.08) 0.20  KIR B/x with 2DS5+ 416 1.04 (0.83-1.30) 0.74 KIR B/x with 2DL2+ 482 0.79 (0.64-0.97) 0.025  KIR B/x with 2DL2+ 664 1.09 (0.88-1.35) 0.43 KIR B/x with 2DL5+ 418 0.83 (0.68-1.02) 0.075  KIR B/x with 2DL5+ 649 1.03 (0.84-1.27) 0.75 KIR B/x with 3DS1+ 317 0.86 (0.71-1.05) 0.15  KIR B/x with 3DS1+ 505 1.07 (0.86-1.32) 0.56 Bolded p values are independently significant p<0.05/7=0.007    

KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation

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KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation

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