Background
Methods
Setting
Study type and study population
Definition of matching criteria
Definition of analyzed variables
Statistical methods
Results
Identification of PTLD cases and their inclusion into matched-pair analysis
Clinicopathological characteristics of analyzed PTLD cases
Variable | Distribution |
---|---|
Age at transplantation in years | Median: 12.7 (0.4–65.4); mean: 22.3 |
Time to diagnosis after transplantation in years | Median: 2.1 (0.3–19); mean: 3.8 |
Age at PTLD diagnosis in years | Median: 15.7 (0.8–70.8); mean: 26.1 |
Age > 60 years at PTLD diagnosis |
n = 4 (11.1 %) |
Age < 10 years at PTLD diagnosis |
n = 14 (38.9 %) |
Age < 5 years at PTLD diagnosis |
n = 11 (30.6 %) |
Late PTLD (>365 days after Tx) |
n = 24 (66.7 %) |
Very early PLTD (<183 days after Tx) |
n = 4 (11.1 %) |
Ciclosporine at PTLD diagnosis |
n = 15 (41.7 %) |
Tacrolimus at PTLD diagnosis |
n = 16 (44.4 %) |
CNI-free immunosuppression at PTLD diagnosis |
n = 5 (13.9 %) |
Mycophenolat at PTLD diagnosis |
n = 19 (52.8 %) |
Steroids at PTLD diagnosis |
n = 29 (80.6 %) |
Steroid-free immunosuppression at PTLD diagnosis |
n = 7 (19.4 %) |
mTOR inhibitors at PTLD diagnosis |
n = 1 (2.8 %) |
Number of graft rejections prior to PTLD diagnosis | Median: 0 (0–2); mean: 0.44 |
Number of graft rejections after PTLD diagnosis | Median: 0 (0–1); mean: 0.25 |
Polymorphic PTLD |
n = 5 (13.9 %) |
Monomorphic PTLD |
n = 28 (77.8 %) |
Pure B cell neoplasm |
n = 29 (80.6 %) |
Diffuse large B cell neoplasm |
n = 20 (55.6 %) |
CD20 expression in tumor |
n = 32 (88.9 %) |
EBV latent membrane protein or EBV-encoded RNA in tumor cells |
n = 26 (100.0 %a, 10 cases missing data) |
Detection of monoclonal disease |
n = 9 (52.9 %a, 19 cases missing data) |
Extranodal disease |
n = 24 (66.7 %) |
Graft organ involvement |
n = 4 (11.1 %) |
CNS involvement |
n = 7 (19.4 %) |
Primary CNS lymphoma |
n = 4 (11.1 %) |
Bone marrow involvement |
n = 6 (16.7 %) |
Gastro-intestinal involvement |
n = 14 (38.9 %) |
Lung involvement |
n = 3 (8.3 %) |
Skin involvement |
n = 0 (0.0 %) |
Number of sites involved | Median: 2 (1–6); mean: 2.5 |
Stage IV disease |
n = 25 (69.4 %) |
B-symptoms at PTLD diagnosis |
n = 4 (11.1 %) |
Lactate dehydrogenase elevated at PTLD diagnosis |
n = 23 (71.9 %a, 4 cases missing data) |
Hypoalbuminemia at PTLD diagnosis |
n = 17 (65.4 %a, 10 cases missing data) |
EBV IgG at Tx |
n = 14 (45.2 %a, 5 cases missing data) |
EBV IgM at Tx |
n = 1 (3.3 %a, 6 cases missing data) |
EBV serology or DNA positive at PTLD diagnosis |
n = 31 (100.0 %a, 5 cases missing data) |
EBV DNA at PTLD diagnosis |
n = 29 (96.7 %a, 6 cases missing data) |
EBV IgG at PTLD diagnosis |
n = 21 (77.8 %a, 9 cases missing data) |
CMV IgG at Tx |
n = 12 (35.3 %a, 2 cases missing data) |
CMV IgM at Tx |
n = 3 (9.7 %a, 5 cases missing data) |
CMV pp65 at Tx |
n = 1 (3.8 %a, 10 cases missing data) |
CMV serology or DNA positive at PTLD diagnosis |
n = 23 (100 %a, 13 cases missing data) |
CMV pp65 at PTLD diagnosis |
n = 1 (4.2 %a, 12 cases missing data) |
CMV DNA at PTLD diagnosis |
n = 4 (22.2 %a, 18 cases missing data) |
CMV IgM at PTLD diagnosis |
n = 7 (30.4 %a, 13 cases missing data) |
CMV IgG at PTLD diagnosis |
n = 21 (77.8 %a, 9 cases missing data) |
Survival in PTLD versus matched non-PTLD patients
Variables (+)/(−)a
| Nr. of analyzed matched pairs in % | Concordant pairs | Discordant pairs |
p valueb
| ||
---|---|---|---|---|---|---|
Combination PTLD (+) and non-PTLD (+) | Combination PTLD (−) and non-PTLD (−) | Combination PTLD (−) and non-PTLD (+) | Combination PTLD (+) and non-PTLD (−) | |||
Death | 100.0 | 2 | 22 |
1
|
11
|
0.004
|
Subsequent re-transplants | 100.0 | 1 | 26 | 5 | 4 | 0.739 |
Living Donor | 100.0 | 4 | 18 | 5 | 9 | 0.285 |
BMI >30 kg/m2
| 100.0 | 0 | 32 | 2 | 1 | 0.564 |
Diabetes | 100.0 | 0 | 32 | 2 | 2 | 1.000 |
Alcohol abuse | 100.0 | 0 | 34 | 2 | 0 | n.d. |
Active Smoking | 100.0 | 0 | 31 | 2 | 3 | 0.655 |
COPD | 100.0 | 0 | 35 | 1 | 0 | n.d. |
Recipient EBV IgG at Tx | 86.1 | 12 | 13 | 4 | 2 | 0.414 |
Recipient CMV IgG at Tx | 91.7 | 9 | 15 | 6 | 3 | 0.317 |
Donor CMV IgG at Tx | 97.2 | 13 | 8 | 5 | 9 | 0.285 |
Recipient Anti-HCV at Tx | 61.1 | 0 | 22 | 0 | 0 | n.d. |
Anti-CMV treatment after Tx | 100.0 | 10 | 9 | 7 | 10 | 0.467 |
Ganciclovir/valganciclovir after Tx | 100.0 | 9 | 11 | 7 | 9 | 0.617 |
Pre-transplant malignancy | 100.0 | 2 | 34 | 0 | 0 | 1.000 |
Pre-transplant HCC | 100.0 | 2 | 34 | 0 | 0 | 1.000 |
Non-PTLD malignancy after Tx | 100.0 | 0 | 31 | 2 | 3 | 0.655 |
Breast cancer after Tx | 100.0 | 0 | 35 | 0 | 1 | n.d. |
Pre-transplant dialysis | 100.0 | 12 | 20 | 2 | 2 | 1.000 |
Donor HLA A26, B38 | 75.0 | 0 | 25 | 0 | 2 | n.d. |
Donor HLA A1 | 75.0 | 1 | 15 | 5 | 6 | 0.763 |
Donor HLA B8 | 75.0 | 1 | 21 | 3 | 2 | 0.655 |
Donor HLA DR3 | 75.0 | 1 | 20 | 4 | 2 | 0.414 |
Recipient HLA A26, B38 | 52.8 | 0 | 18 | 0 | 1 | n.d. |
Recipient HLA A2 | 52.8 | 6 | 2 |
10
|
1
|
0.007
|
Recipient HLA A11 | 52.8 | 0 | 15 | 3 | 1 | 0.317 |
Recipient HLA B5 | 52.8 | 0 | 15 | 2 | 2 | 1.000 |
Recipient HLA B18 | 52.8 | 0 | 16 | 3 | 0 | n.d. |
Recipient HLA B21 | 52.8 | 0 | 18 | 1 | 0 | n.d. |
Recipient HLA B35 | 52.8 | 1 | 12 | 4 | 2 | 0.414 |
Recipient HLA A3 | 52.8 | 1 | 10 | 4 | 4 | 1.000 |
Recipient HLA DR27 | 52.8 | 0 | 19 | 0 | 0 | n.d. |
HLA A locus mismatching | 47.2 | 7 | 2 | 3 | 5 | 0.480 |
HLA B locus mismatching | 47.2 | 10 | 0 | 3 | 4 | 0.706 |
HLA DR locus mismatching | 47.2 | 12 | 2 | 2 | 1 | 0.564 |
Anti-thymocyte globulin after Tx | 86.1 | 0 | 30 | 1 | 0 | n.d. |
Basiliximab therapy after Tx | 86.1 | 6 | 11 | 7 | 7 | 1.000 |
Daclizumab therapy after Tx | 86.1 | 0 | 29 | 1 | 1 | 1.000 |
Tacrolimusc after Tx | 100.0 | 5 | 18 |
3
|
10
|
0.052
|
Ciclosporinec after Tx | 100.0 | 17 | 5 | 10 | 4 | 0.109 |
MMFc after Tx | 100.0 | 10 | 15 | 5 | 6 | 0.763 |
Myforticc after Tx | 100.0 | 0 | 35 | 0 | 1 | n.d. |
Steroidsc after Tx | 100.0 | 32 | 1 | 1 | 2 | 0.564 |
Sirolimusc after Tx | 100.0 | 0 | 34 | 1 | 1 | 1.000 |
Everolimusc after Tx | 100.0 | 0 | 34 | 1 | 1 | 1.000 |
Azathioprinc after Tx | 100.0 | 1 | 33 | 2 | 0 | 0.157 |
Tacrolimus at PTLDd
| 100.0 | 7 | 14 | 6 | 9 | 0.439 |
Ciclosporine at PTLDd
| 100.0 | 12 | 12 | 9 | 3 | 0.083 |
CNI-free treatment at PTLDd
| 100.0 | 1 | 30 | 1 | 4 | 0.180 |
Variable | PTLD mean | Non-PTLD mean | Mean difference of Non-PTLD minus PTLD |
p valuea
| Standard error of mean difference |
---|---|---|---|---|---|
Survival after Tx in years | 7.74 | 9.98 | 2.24 |
0.004
| 0.72 |
PTLD-free survival in years | 3.99 | 9.98 | 5.99 |
<0.001
| 0.76 |
Number of subsequent re-transplants | 0.17 | 0.17 | 0.00 | 1.000 | 0.10 |
CIT in minutes | 658.07 | 627.07 | −31.00 | 0.756 | 99.05 |
BMI in kg/m2
| 20.05 | 20.13 | 0.09 | 0.890 | 0.62 |
Number of episodes of graft rejection | 0.71 | 1.17 | 0.46 | 0.118 | 0.29 |
Number of episodes of EBV de novo infections or reactivations | 0.50 | 0.50 | 0.00 | 1.000 | 0.15 |
Number of episodes of CMV de novo infections or reactivations | 1.47 | 0.75 | −0.72 |
0.042
| 0.34 |
Duration of pre-Tx dialysis in years | 4.02 | 4.65 | 0.63 | 0.561 | 1.06 |
Number of HLA A locus recipient-donor mismatches | 0.76 | 0.71 | −0.06 | 0.791 | 0.22 |
Number of HLA B locus recipient-donor mismatches | 1.12 | 1.06 | −0.06 | 0.805 | 0.23 |
Number of HLA DR locus recipient-donor mismatches | 0.94 | 1.06 | 0.12 | 0.431 | 0.15 |
Overall number of HLA recipient-donor mismatches | 2.82 | 2.82 | 0.00 | 1.000 | 0.51 |
Daily dose of tacrolimus in mgb after Tx | 3.74 | 1.62 | −2.12 |
0.052
| 1.05 |
Blood level of tacrolimus in ng/mlb after Tx | 9.97 | 8.13 | −1.83 | 0.734 | 4.69 |
Daily dose of ciclosporine in mgb after Tx | 176.17 | 183.06 | 6.89 | 0.832 | 32.24 |
C0 blood level of ciclosporine in μg/lb after Tx | 218.46 | 195.91 | −22.55 | 0.230 | 17.63 |
C2 blood level of ciclosporine in μg/lb after Tx | 1183.0 | 1168.5 | −14.5 | 0.909 | 100.5 |
Daily dose of MMF in mg afterb after Tx | 545.00 | 551.67 | 6.67 | 0.967 | 161.43 |
Daily dose of prednisolone in mgb after Tx | 11.13 | 10.99 | −0.14 | 0.916 | 1.31 |
Daily dose of sirolimus inb after Tx | 0.06 | 0.06 | 0.00 | 1.000 | 0.08 |
Daily dose of everolimus in mgb after Tx | 0.06 | 0.14 | 0.08 | 0.585 | 0.15 |
Daily dose of azathioprine in mgb after Tx | 2.08 | 2.78 | 0.69 | 0.160 | 0.48 |
Tacrolimus treatment in months c
| 12.47 | 15.62 | 3.15 | 0.596 | 5.87 |
Tacrolimus treatment in % of time of immunosuppressionc
| 46.87 | 33.45 | −13.42 | 0.231 | 11.00 |
Ciclosporine treatment in monthsc
| 27.16 | 25.58 | −1.58 | 0.737 | 4.67 |
Ciclosporine treatment in % of time of immunosuppressionc
| 46.25 | 59.70 | 13.45 | 0.180 | 9.83 |
CNI-free treatment in monthsc
| 6.96 | 5.29 | −1.67 | 0.628 | 3.41 |
CNI-free treatment in % of time of immunosuppressionc
| 7.81 | 6.69 | −1.11 | 0.803 | 4.42 |