Table S1: Preparative regimen, Graft and GVHD prophylaxis for Patients
REGIMEN / GRAFT / GVHD PROPHYLAXISMRD / CY, TBI, ATG / BM OR PBMC / CSA & MMF or
MTX & FK
BU, CY, ATG / BM OR PBMC
MURD / CY, TBI, ATG / BM OR PBMC / CSA & MMF or
MTX & FK
BU, CY, ATG / BM OR PBMC
HAPLO / CLO, THIO, MEL / TCD PBMC / OKT3 & MMF
FLU, THIO, MEL / TCD PBMC / CAMPATH & MMF
UCB / FLU, CY, TBI / UCB / CSA & MMF
*CY cyclophosphamide, TBI total body irradiation, ATG anti-thymoglobulin, BU busulfan, CLO clofarabine, THIO thiotepa, MEL melphalan, TCD T cell deplete, BM bone marrow, PBMC peripheral blood mononuclear cells, CSA cyclosporin, MMF mycophenolate, MTX methotrexate, FK tacrolimus, Muromonab-CD3 (OKT3)
Table S2A Patient Characteristics for Patients undergoing MRD and MURD HSCT and Distribution in the Low/Normal vs. High γδ T cell Group
Variable / Category / OverallN=64 / Low γδ
N=57 / High γδ
N=7 / P-
value
Donor / 0.042
MRD / 22 (34.4%) / 17 (29.8%) / 5 (71.4%) / .
MURD / 42 (65.6%) / 40 (70.2%) / 2 (28.6%) / .
Age / 0.169
Mean ± SD / 11.7 ± 5.3 / 12.0 ± 5.1 / 9.0 ± 5.97 / .
Median (range) / 11.3 (1.6-25.2) / 11.3 (2.2-25.2) / 7.6 (1.6-16.3) / .
Gender / 1.00
Female / 33 (51.6%) / 29 (50.9%) / 4 (57.1%) / .
Male / 31 (48.4%) / 28 (49.1%) / 3 (42.9%) / .
Diagnosis / 0.428
ALL / 38 (59.4%) / 35 (61.4%) / 3 (42.9%) / .
AML / 26 (40.6%) / 22 (38.6%) / 4 (57.1%) / .
GVHD / 0.702
No / 40 (62.5%) / 35 (61.4%) / 5 (71.4%)
Yes / 24 (37.5%) / 22 (38.6%) / 2 (28.6%)
Relapse / 1.000
No / 57 (89.1%) / 50 (87.7%) / 7 (100.0%) / .
Yes / 7 (10.9%) / 7 (12.3%) / .
Survival / 0.178
Alive / 48 (75.0%) / 41 (71.9%) / 7 (100.0%) / .
Expired / 16 (25.0%) / 16 (28.1%) / .
Infection / 0.454
No / 36 (56.3%) / 31 (54.4%) / 5 (71.4%) / .
Yes / 28 (43.8%) / 26 (45.6%) / 2 (28.6%) / .
CD3 / 0.006
Mean ± SD / 1.5 ± 1.27 / 1.3 ± 1.19 / 2.7 ± 1.32 / .
Median (range) / 1.1 (0.0-5.2) / 0.9 (0.0-5.2) / 2.4 (1.1-4.9) / .
CD19 / 0.286
Mean ± SD / 0.3 ± 0.31 / 0.3 ± 0.29 / 0.4 ± 0.46 / .
Median (range) / 0.2 (0.0-1.4) / 0.2 (0.0-1.2) / 0.3 (0.1-1.4) / .
CD4 / 0.031
Mean ± SD / 0.5 ± 0.43 / 0.5 ± 0.36 / 1.0 ± 0.65 / .
Median (range) / 0.4 (0.0-2.0) / 0.4 (0.0-1.5) / 0.9 (0.3-2.0) / .
CD8 / 0.020
Mean ± SD / 0.9 ± 1.06 / 0.8 ± 1.04 / 1.6 ± 1.03 / .
Median (range) / 0.6 (0.0-4.4) / 0.5 (0.0-4.4) / 1.7 (0.6-3.2) / .
NK / 0.533
Mean ± SD / 0.4 ± 0.26 / 0.4 ± 0.27 / 0.4 ± 0.17 / .
Median (range) / 0.3 (0.0-1.5) / 0.3 (0.0-1.5) / 0.4 (0.1-0.6) / .
γδ / <0.001
Mean ± SD / 0.1 ± 0.10 / 0.1 ± 0.04 / 0.3 ± 0.11 / .
Median (range) / 0.1 (0.0-0.6) / 0.1 (0.0-0.2) / 0.3 (0.2-0.6) / .
P * values indicate statistical significance observed between the low/normal vs. high γδ T cell group
Table S2B. Patient Characteristics for Patients Undergoing UCB and HAPLO HSCT and Distribution in the Low/Normal vs. High γδ T cell Group
Variable / Category / OverallN = 38 / Low γδ
N = 34 / High γδ
N = 4 / P-value
Donor / 1.000
UCB / 6 (15.8%) / 6 (17.6%) / 0 (0.0%) / .
HAPLO / 32 (84.2%) / 28 (82.4%) / 4 (100.0%) / .
Age / 0.981
Mean ± SD / 8.5 ± 6.46 / 8.4 ± 6.62 / 9.1 ± 5.76 / .
Median (Range) / 8.6 (0.6-18.8) / 8.0 (0.6-18.8) / 11.4 (0.6-12.9) / .
Gender / 1.000
Female / 11 (28.9%) / 10 (29.4%) / 1 (25.0%) / .
Male / 27 (71.1%) / 24 (70.6%) / 3 (75.0%) / .
Diagnosis / 0.124
ALL / 22 (57.9%) / 18 (52.9%) / 4 (100.0%) / .
AML / 16 (42.1%) / 16 (47.1%) / 0 (0.0%) / .
GVHD / 1.000
1-2 / 13 (34.2%) / 12 (35.3%) / 1 (25.0%) / .
3-4 / 3 (7.9%) / 3 (8.8%) / 0 (0.0%) / .
No / 22 (57.9%) / 19 (55.9%) / 3 (75.0%) / .
Relapse / 1.000
No / 25 (65.8%) / 22 (64.7%) / 3 (75.0%) / .
Yes / 13 (34.2%) / 12 (35.3%) / 1 (25.0%) / .
Survival / 0.328
Alive / 18 (47.4%) / 15 (44.1%) / 3 (75.0%) / .
Expired / 20 (52.6%) / 19 (55.9%) / 1 (25.0%) / .
Infections / 0.018
No / 15 (39.5%) / 11 (32.4%) / 4 (100.0%) / .
Yes / 23 (60.5%) / 23 (67.6%) / 0 (0.0%) / .
CD3 / 0.021
Mean ± SD / 1.0 ± 0.72 / 0.9 ± 0.66 / 1.9 ± 0.74 / .
Median (Range) / 0.8 (0.0-2.6) / 0.8 (0.0-2.6) / 2.0 (1.0-2.6) / .
CD19 / 0.187
Mean ± SD / 0.5 ± 1.03 / 0.5 ± 1.06 / 0.6 ± 0.81 / .
Median (Range) / 0.1 (0.0-5.5) / 0.1 (0.0-5.5) / 0.3 (0.2-1.9) / .
CD4 / 0.147
Mean ± SD / 0.5 ± 0.43 / 0.5 ± 0.40 / 0.8 ± 0.60 / .
Median (Range) / 0.3 (0.0-1.6) / 0.3 (0.0-1.6) / 0.8 (0.1-1.6) / .
CD8 / 0.025
Mean ± SD / 0.5 ± 0.49 / 0.4 ± 0.47 / 1.0 ± 0.40 / .
Median (Range) / 0.4 (0.0-2.5) / 0.4 (0.0-2.5) / 0.8 (0.7-1.6) / .
NK / 0.905
Mean ± SD / 0.5 ± 0.48 / 0.5 ± 0.29 / 1.0 ± 1.27 / .
Median (Range) / 0.5 (0.0-2.9) / 0.5 (0.0-1.4) / 0.5 (0.2-2.9) / .
γδ T cells / 0.001
Mean ± SD / 0.1 ± 0.08 / 0.1 ± 0.06 / 0.3 ± 0.02 / .
Median (Range) / 0.1 (0.0-0.3) / 0.0 (0.0-0.2) / 0.3 (0.2-0.3) / .
P * values indicate statistical significance observed between the low/normal vs. high γδ T cell group
Table S3A: Univariate & Multivariate Analysis of Co-variates and Association with γδ T cells for Patients undergoing MRD and MURD HSCT
Variable / Category / Estimate / P-value / Lower 95% CI / Upper 95% CIUnivariate Analysis
Donor / MRD vs. MURD / 0.071 / 0.006 / 0.021 / 0.121
Age / -0.004 / 0.120 / -0.008 / 0.001
Gender / Female vs Male / 0.026 / 0.303 / -0.024 / 0.076
Diagnosis / ALL vs. AML / -0.017 / 0.510 / -0.068 / 0.034
Acute GVHD / None / 0.025 / 0.332 / -0.077 / 0.026
Grade 1-2 / -0.021 / 0.490 / -0.082 / 0.040
Grade 3-4 / -0.032 / 0.392 / -0.107 / 0.042
Chronic GVHD / Yes vs No / -0.023 / 0.563 / -0.104 / 0.057
Relapse / Yes vs No / -0.049 / 0.224 / -0.130 / 0.030
Status / Alive vs Expired / 0.062 / 0.032 / 0.005 / 0.118
Infection / Yes vs No / -0.047 / 0.061 / -0.097 / 0.002
GVHD
Prophylaxis / CSA & MMF / 0.053 / 0.377 / -0.066 / 0.172
MTX & FK / 0.047 / 0.194 / -0.025 / 0.119
ATG / -0.014 / 0.628 / -0.074 / 0.045
Immune
Recovery / CD3 / 0.028 / 0.004 / 0.009 / 0.047
CD4 / 0.104 / <0.001 / 0.051 / 0.158
CD 8 / 0.019 / 0.119 / -0.005 / 0.042
CD19 / 0.070 / 0.085 / -0.010 / 0.150
NK / 0.040 / 0.417 / -0.057 / 0.137
Multivariate Analysis
Donor / MRD vs MURD / 0.05 / 0.01 / 0.009 / 0.10Immune Recovery / CD3 / 0.01 / 0.33 / -0.012 / 0.03
CD4 / 0.06 / 0.06 / -0.003 / 0.14
Table S3B. Analysis of Co-variates and Association with γδ T cell for Patients undergoing UCB and HAPLO HSCT
Variable / Category / Estimate / P-value / Lower 95% CI / Upper 95% CIDonor / UCB vs. HAPLO / -0.082 / 0.024* / -0.153 / -0.012
Age / Age at HSCT / -0.001 / 0.544 / -0.006 / 0.003
Gender / Female vs. Male / 0.020 / 0.508 / -0.041 / 0.081
Diagnosis / ALL vs. AML / 0.037 / 0.179 / -0.018 / 0.092
Acute GVHD / None / . / 0.793 / . / .
Grade 1-2 / -0.005 / 0.858 / -0.066 / 0.055
Grade 3-4 / -0.036 / 0.499 / -0.141 / 0.070
Chronic GVHD / Yes vs. No / 0.066 / 0.071 / -0.006 / 0.139
Relapse / Yes vs. No / 0.012 / 0.688 / -0.047 / 0.070
Status / Alive vs. Expired / 0.050 / 0.063 / -0.003 / 0.103
Infection / Yes vs. No / 0.038 / 0.170 / -0.017 / 0.093
GVHD
Prophylaxis / CSA & MMF / 0.017 / 0.658 / -0.059 / 0.092
MTX & FK / 0.065 / 0.023 / 0.009 / 0.120
OKT3 ± ATG / 0.034 / 0.575 / -0.089 / 0.158
Immune
Recovery / CD3 / 0.076 / <0.001* / 0.047 / 0.105
CD4 / 0.083 / 0.007* / 0.025 / 0.142
CD 8 / 0.091 / 0.001* / 0.042 / 0.140
CD19 / -0.003 / 0.807 / -0.031 / 0.024
NK / 0.063 / 0.024* / 0.009 / 0.117
Table S4A. Analysis for OS For Patients undergoing MRD and MURD HSCT (Cox-Model)
UNIVARIATE ANALYSISVariable / Category / Estimate / P value / Hazard Ratio (95% CI)
Age / 0.06 / 0.180 / 1.065 (0.971,1.168)
Gender / Female vs. Male / 0.63 / 0.211 / 1.888 (0.686,5.198)
Diagnosis / ALL vs. AML / -0.59 / 0.261 / 0.550 (0.191,1.584)
Donor / MRD vs. MURD / 0.61 / 0.276 / 1.857 (0.598,5.762)
Acute GVHD / Yes vs. No / 0.65 / 0.186 / 1.916 (0.719, 5.110)
Chronic GVHD / Yes vs. No / -0.70 / 0.484 / 0.492 (0.065, 3.735)
Relapse / Yes vs. No / 2.27 / <0.001 / 9.73 (3.47, 27.35)
Infection / Yes vs. No / 1.05 / 0.035 / 2.863 (1.031, 7.948)
Immune Recovery / CD3 / -1.83 / 0.002 / 0.160 (0.052, 0.494)
CD4 / -4.75 / <0.001 / 0.009 (0.001, 0.135)
CD 8 / -2.22 / 0.021 / 0.108 (0.017, 0.675)
γδ / -24.5 / 0.01 / <0.001 (<0.001, 0.002)
CD19 / -2.08 / 0.084 / 0.124 (0.011, 1.406)
NK / -1.17 / 0.348 / 0.309 (0.027, 3.593)
MULTIVARIATE ANALYSIS
Variable / Category / Estimate / P value / Hazard Ratio (95% CI)Immune Recovery / γδ / -13.4 / 0.30 / <0.001(<0.001,133743.9)
CD3 / 5.31 / 0.30 / 202.8 (0.009, 4607001)
CD4 / -7.97 / 0.13 / <0.001 (<0.001, 13.45)
CD8 / -5.54 / 0.26 / 0.004 (<0.001, 72.68)
Relapse / Yes / 1.55 / 0.03 / 4.73 (1.09, 20.6)
Infections / Yes / 0.82 / 0.24 / 2.28 (0.57, 9.10)
Table S4B. Univariate Analysis for OS for Patients Undergoing UCB and HAPLO HSCT
Variable / Category / Estimate / P value / Hazard Ratio (95% CI)Age / Age at HSCT / 0.02051 / 0.577 / 1.021 (0.950,1.097)
Gender / Female vs Male / -0.16771 / 0.732 / 0.846 (0.323,2.210)
Diagnosis / ALL vs AML / 0.66649 / 0.139 / 1.947 (0.805,4.710)
Donor / UCB vs HAPLO / -0.53917 / 0.340 / 0.583 (0.193,1.763)
Acute GVHD / Yes vs No / 0.18899 / 0.673 / 1.208 (0.502,2.906)
Chronic GVHD / Yes vs No / 0.05744 / 0.918 / 1.059 (0.354,3.172)
Relapse / Yes vs No / 0.76760 / 0.087 / 2.155 (0.895,5.190)
Infection / Yes vs No / 0.16671 / 0.723 / 1.181 (0.471,2.965)
Immune Recovery / CD3 / -0.96843 / 0.016* / 0.380 (0.170,0.848)
CD4 / -1.22177 / 0.066 / 0.295 (0.078,1.118)
CD 8 / -1.25234 / 0.091 / 0.286 (0.070,1.166)
NK / -0.37425 / 0.318 / 0.688 (0.326,1.450)
CD19 / -0.16847 / 0.736 / 0.845 (0.316,2.259)
γδ / -9.20066 / 0.014* / 0.000 (0.000,0.209)
Table S4C. Univariate & Multivariate Analysis for Variables Associated with OS After HSCT
All Patients (Cox-Model)
Univariate AnalysisVariable / Category / Estimate / P value / Hazard Ratio (95% CI)
Donor / 0.006*
CORD / . / .
HAPLO / -0.5571 / 0.322 / 0.573 (0.190, 1.726)
MRD / -1.9156 / 0.007 / 0.147 (0.036, 0.596)
MURD / -1.2879 / 0.027 / 0.276 (0.088, 0.864)
Age / 0.0130 / 0.659 / 1.013 (0.956, 1.073)
Gender / Female vs. Male / 0.4904 / 0.166 / 1.633 (0.816, 3.266)
Diagnosis / ALL vs. AML / 0.0632 / 0.851 / 1.065 (0.552, 2.057)
GVHD Prophylaxis / CSA & MMF / 0.5988 / 0.411 / 1.820 (0.437, 7.581)
MTX & FK / -0.2681 / 0.434 / 0.765 (0.391, 1.497)
ATG / -0.0767 / 0.874 / 0.926 (0.359, 2.387)
Acute GVHD / None / 0.195
Grade 1-2
Grade 3-4 / 0.4528 / 0.366 / 1.573 (0.589,4.201)
Chronic GVHD / Yes vs. No / -0.3587 / 0.336 / 0.699 (0.336,1.450)
Relapse / Yes vs. No / 1.6580 / <0.001* / 5.249 (2.681,10.28)
Infection / Yes vs. No / 0.7735 / 0.023* / 2.167 (1.092,4.300)
Subgroups / 0.021
Bacterial
Fungal Infection / -13.8357 / 0.991 / 0.000 (0.000)
None / -1.0922 / 0.004 / 0.335 (0.159, 0.707)
Viral Infection / -0.6944 / 0.113 / 0.499 (0.211, 1.180)
Bacterial Infection / Yes vs. No / -0.9710 / 0.003 / 0.379 (0.195, 0.735)
Viral Infection / Yes vs. No / -0.0352 / 0.930 / 0.965 (0.438, 2.127)
Fungal / Yes vs. No / 13.0201 / 0.535 / 451E3 (0.000)
Immune Recovery / CD3 / -1.2713 / <0.001* / 0.280 (0.151, 0.521)
CD4 / -2.3547 / <0.001* / 0.095 (0.027, 0.338)
CD 8 / -1.7301 / 0.003* / 0.177 (0.060,0.526)
CD19 / -0.4788 / 0.291 / 0.620 (0.259,1.482)
NK / 0.0241 / 0.957 / 1.024 (0.433, 2.425)
γδ T cells / -12.836 / 0.001* / 0.000 (0.000,0.008)
Multivariate Analysis
Parameter / Parameter
Estimate / PrChiSq / Hazard
Ratio / 95% Hazard Ratio Confidence Limits
Donor / 0.356
HAPLO / -0.376 / 0.629 / 0.686 / 0.149 / 3.159
MRD / -1.286 / 0.122 / 0.276 / 0.054 / 1.410
MURD / -0.606 / 0.382 / 0.546 / 0.140 / 2.122
Relapse / 1.361 / 0.001* / 3.899 / 1.837 / 8.275
Infection / 0.186 / 0.645 / 1.204 / 0.546 / 2.655
γδ T cells / -10.115 / 0.059* / 0.000 / 0.000 / 1.464
CD 3 / 3.063 / 0.396 / 21.401 / 0.018 / 25399
CD4 / -4.646 / 0.209 / 0.010 / 0.000 / 13.444
CD 8 / -3.799 / 0.303 / 0.022 / 0.000 / 30.763
Table S5. Sensitivity and Specificity of Developing Infections For Patients with Elevated γδ T cells
Infection / Overall / Low\Normal / High / P-value / Sensitivity and SpecificityALL PATIENTS
No / 51 (50.0%) / 42 (46.2%) / 9 (81.8%) / 0.05 / 17.6% sensitivity
Yes / 51 (50.0%) / 49 (53.8%) / 2 (18.2%) / 96.1% specificity
MRD and MURD HSCT
No / 36 (56.3%) / 31 (54.4%) / 5 (71.4%) / 0.40 / *
Yes / 28 (43.8%) / 26 (45.6%) / 2 (28.6%) / *
UCT and HAPLO HSCT
No / 15 (39.5%) / 11 (32.4%) / 4 (100.0%) / 0.018 / 26.7% sensitivity, 100% specificityYes / 23 (60.5%) / 23 (67.6%)
*Here p-value is not significant, hence sensitivity and specificity are not reported.