Abstract
The outcome of PTLD has a reported approximate 3-year (yr) overall survival (OS) rate of 35%–40% in the pre-RTX era (
JCO
2001
; 19
:772
performance status (PS),
serum albumin,
>1 extranodal (EN) site,
bone marrow (BM) involvement,
CNS disease, and
RTX as part of initial therapy (alone or combined with chemotherapy).
Neither EBV status nor time to PTLD predicted outcome.
Table 1. PTLD characteristics and univariate predictors of EFS and OS (n=81).
Variable (at dx) . | Pt characteristics . | PFS . | OS . | ||||
---|---|---|---|---|---|---|---|
. | . | No. . | % . | HR* . | P . | HR* . | P . |
*Prognostic factors were tested for association with survival by proportional hazards analysis. Hazard ratios (HRs) >1 indicate a poor prognosis, while HRs <1 indicate a good prognosis. | |||||||
**Analysis was monomorphic PTLD (n=55) vs polymorphic and reactive (n=26). | |||||||
***Analysis combined rituximab alone and rituximab/chemotherapy-treated pts (n=60) vs all other therapy (n=21). | |||||||
n/a = not available. | |||||||
Table 2 shows 3-yr survival rates based on these variables. On multivariate analysis, 4 factors remained significant: | |||||||
1) RTX (EFS HR 0.26 (CI 0.11–0.60), p=0.002; OS HR 0.23 (CI 0.090.56), p=0.001), | |||||||
2) >1 EN site (EFS HR 2.15 (CI 1.04–4.42), p=0.04; OS HR 2.14 (CI 1.01–4.54), p=0.047), | |||||||
3) low albumin (EFS HR 3.19 (CI 1.17–8.72), p=0.02; OS HR 4.73 (CI 1.39–16.16), p=0.01), and | |||||||
4) CNS (EFS HR 4.48 (CI 1.80–11.17), p=0.01; OS HR 3.90 (CI 1.54–9.88), p=0.004). | |||||||
A prognostic model based on 3 factors: >1 EN site, albumin, and CNS disease was constructed (EFS p=0.008, OS=p=0.006), suggesting that pts with differential outcomes can be identified. In summary, we show that the introduction of RTX appears to have improved the outcome of PTLD compared to published data. However, a significant minority of pts still experience short survival. Clinical features at PTLD dx can predict outcome and should be incorporated into future therapeutic strategies. | |||||||
Kidney | 37 | 46 | |||||
Kidney-pancreas | 10 | 12 | |||||
SOT | Pancreas | 4 | 5 | 0.74 | 0.38 | 0.71 | 0.36 |
Liver | 17 | 21 | |||||
Heart | 8 | 10 | |||||
Lung | 5 | 6 | |||||
Time to PTLD | Early (<1 yr) | 30 | 37 | 1.02 | 0.95 | 0.91 | 0.81 |
Late (> 1 yr) | 51 | 63 | |||||
Monomorphic | 55 | 68 | |||||
Histology** | Polymorphic | 22 | 27 | 1.61 | 0.27 | 2.18 | 0.11 |
Plasmacytic/reactive | 4 | 5 | |||||
EBV + (tumor) | Yes | 39 | 48 | ||||
No | 30 | 37 | 1.09 | 0.82 | 0.82 | 0.64 | |
n/a | 12 | 15 | |||||
PS | 2–4 | 25 | 31 | 2.87 | 0.002 | 3.31 | 0.001 |
0–1 | 56 | 69 | |||||
CNS involvement | Yes | 10 | 12 | 2.57 | 0.03 | 2.47 | 0.050 |
No | 71 | 88 | |||||
BM involvement | Yes | 12 | 15 | ||||
No | 58 | 72 | 3.30 | 0.003 | 3.48 | 0.003 | |
n/a | 11 | 13 | |||||
EN > 1 | Yes | 29 | 36 | ||||
No | 50 | 62 | 2.01 | 0.04 | 2.19 | 0.03 | |
n/a | 2 | 2 | |||||
High LDH | Yes | 49 | 60 | ||||
No | 27 | 33 | 1.64 | 0.21 | 2.00 | 0.11 | |
n/a | 5 | 7 | |||||
Yes | 56 | 69 | |||||
Low serum albumin | No | 24 | 30 | 3.02 | 0.02 | 4.72 | 0.01 |
n/a | 1 | 1 | |||||
IPI | 2–4 | 47 | 58 | ||||
0–2 | 33 | 41 | 2.04 | 0.053 | 1.76 | 0.16 | |
n/a | 1 | 1 | |||||
Immune suppression alone | 7 | 9 | |||||
Treatment*** | Radiation or surgery alone | 2 | 2 | ||||
Chemotherapy alone | 12 | 15 | 0.28 | 0.003 | 0.30 | 0.001 | |
Rituximab alone | 26 | 32 | |||||
Rituximab/chemotherapy | 34 | 42 |
Variable (at dx) . | Pt characteristics . | PFS . | OS . | ||||
---|---|---|---|---|---|---|---|
. | . | No. . | % . | HR* . | P . | HR* . | P . |
*Prognostic factors were tested for association with survival by proportional hazards analysis. Hazard ratios (HRs) >1 indicate a poor prognosis, while HRs <1 indicate a good prognosis. | |||||||
**Analysis was monomorphic PTLD (n=55) vs polymorphic and reactive (n=26). | |||||||
***Analysis combined rituximab alone and rituximab/chemotherapy-treated pts (n=60) vs all other therapy (n=21). | |||||||
n/a = not available. | |||||||
Table 2 shows 3-yr survival rates based on these variables. On multivariate analysis, 4 factors remained significant: | |||||||
1) RTX (EFS HR 0.26 (CI 0.11–0.60), p=0.002; OS HR 0.23 (CI 0.090.56), p=0.001), | |||||||
2) >1 EN site (EFS HR 2.15 (CI 1.04–4.42), p=0.04; OS HR 2.14 (CI 1.01–4.54), p=0.047), | |||||||
3) low albumin (EFS HR 3.19 (CI 1.17–8.72), p=0.02; OS HR 4.73 (CI 1.39–16.16), p=0.01), and | |||||||
4) CNS (EFS HR 4.48 (CI 1.80–11.17), p=0.01; OS HR 3.90 (CI 1.54–9.88), p=0.004). | |||||||
A prognostic model based on 3 factors: >1 EN site, albumin, and CNS disease was constructed (EFS p=0.008, OS=p=0.006), suggesting that pts with differential outcomes can be identified. In summary, we show that the introduction of RTX appears to have improved the outcome of PTLD compared to published data. However, a significant minority of pts still experience short survival. Clinical features at PTLD dx can predict outcome and should be incorporated into future therapeutic strategies. | |||||||
Kidney | 37 | 46 | |||||
Kidney-pancreas | 10 | 12 | |||||
SOT | Pancreas | 4 | 5 | 0.74 | 0.38 | 0.71 | 0.36 |
Liver | 17 | 21 | |||||
Heart | 8 | 10 | |||||
Lung | 5 | 6 | |||||
Time to PTLD | Early (<1 yr) | 30 | 37 | 1.02 | 0.95 | 0.91 | 0.81 |
Late (> 1 yr) | 51 | 63 | |||||
Monomorphic | 55 | 68 | |||||
Histology** | Polymorphic | 22 | 27 | 1.61 | 0.27 | 2.18 | 0.11 |
Plasmacytic/reactive | 4 | 5 | |||||
EBV + (tumor) | Yes | 39 | 48 | ||||
No | 30 | 37 | 1.09 | 0.82 | 0.82 | 0.64 | |
n/a | 12 | 15 | |||||
PS | 2–4 | 25 | 31 | 2.87 | 0.002 | 3.31 | 0.001 |
0–1 | 56 | 69 | |||||
CNS involvement | Yes | 10 | 12 | 2.57 | 0.03 | 2.47 | 0.050 |
No | 71 | 88 | |||||
BM involvement | Yes | 12 | 15 | ||||
No | 58 | 72 | 3.30 | 0.003 | 3.48 | 0.003 | |
n/a | 11 | 13 | |||||
EN > 1 | Yes | 29 | 36 | ||||
No | 50 | 62 | 2.01 | 0.04 | 2.19 | 0.03 | |
n/a | 2 | 2 | |||||
High LDH | Yes | 49 | 60 | ||||
No | 27 | 33 | 1.64 | 0.21 | 2.00 | 0.11 | |
n/a | 5 | 7 | |||||
Yes | 56 | 69 | |||||
Low serum albumin | No | 24 | 30 | 3.02 | 0.02 | 4.72 | 0.01 |
n/a | 1 | 1 | |||||
IPI | 2–4 | 47 | 58 | ||||
0–2 | 33 | 41 | 2.04 | 0.053 | 1.76 | 0.16 | |
n/a | 1 | 1 | |||||
Immune suppression alone | 7 | 9 | |||||
Treatment*** | Radiation or surgery alone | 2 | 2 | ||||
Chemotherapy alone | 12 | 15 | 0.28 | 0.003 | 0.30 | 0.001 | |
Rituximab alone | 26 | 32 | |||||
Rituximab/chemotherapy | 34 | 42 |
Table 2. Three-year survival (Kaplan-Meier) based on prognostic variables (univariate).
Variable . | 3-year EFS* . | 3-year OS* . |
---|---|---|
*3-year PFS and OS by Kaplan-Meier analysis are reported (and their 95% CIs). | ||
PS | p < 0.0001 | p < 0.0001 |
0–1 | 65% (50%, 77%) | 72% (57%, 82%) |
2–4 | 36% (18%, 54%) | 35% (15%, 56%) |
Albumin | p = 0.002 | p = 0.0004 |
Normal | 75% (49%, 89%) | 85% (59%, 95%) |
Low | 49% (34%, 61%) | 51% (37%, 64%) |
CNS | p = 0.001 | p = 0.004 |
No | 60% (47%, 71%) | 64% (51%, 74%) |
Yes | 30% (7%, 58%) | 40% (12%, 67%) |
Received rituximab | p = 0.0002 | p = 0.001 |
No | 21% (7%, 42%) | 32% (14%, 79%) |
Yes | 69% (55%, 79%) | 71% (57%, 81%) |
BM involvement | p = 0.005 | p = 0.005 |
No | 64% (49%, 75%) | 70% (56%, 80%) |
Yes | 18% (3%, 44%) | 18% (3%, 44%) |
> 1 EN site | p = 0.01 | p = 0.008 |
No | 64% (48%, 76%) | 72% (57%, 82%) |
Yes | 39% (22%, 58%) | 40% (20%, 58%) |
Variable . | 3-year EFS* . | 3-year OS* . |
---|---|---|
*3-year PFS and OS by Kaplan-Meier analysis are reported (and their 95% CIs). | ||
PS | p < 0.0001 | p < 0.0001 |
0–1 | 65% (50%, 77%) | 72% (57%, 82%) |
2–4 | 36% (18%, 54%) | 35% (15%, 56%) |
Albumin | p = 0.002 | p = 0.0004 |
Normal | 75% (49%, 89%) | 85% (59%, 95%) |
Low | 49% (34%, 61%) | 51% (37%, 64%) |
CNS | p = 0.001 | p = 0.004 |
No | 60% (47%, 71%) | 64% (51%, 74%) |
Yes | 30% (7%, 58%) | 40% (12%, 67%) |
Received rituximab | p = 0.0002 | p = 0.001 |
No | 21% (7%, 42%) | 32% (14%, 79%) |
Yes | 69% (55%, 79%) | 71% (57%, 81%) |
BM involvement | p = 0.005 | p = 0.005 |
No | 64% (49%, 75%) | 70% (56%, 80%) |
Yes | 18% (3%, 44%) | 18% (3%, 44%) |
> 1 EN site | p = 0.01 | p = 0.008 |
No | 64% (48%, 76%) | 72% (57%, 82%) |
Yes | 39% (22%, 58%) | 40% (20%, 58%) |
Disclosures: No relevant conflicts of interest to declare.
Author notes
Corresponding author
2008, The American Society of Hematology
2008
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