Summary The prognostic role of CD20 expression and Epstein–Barr virus (EBV) positivity in post‐transplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) in paediatric patients is poorly understood. We retrospectively examined the relationship of CD20 and EBV with the time interval from SOT to PTLD diagnosis, and PTLD‐related event‐free (EFS) and overall survival (OS) in 45 consecutive PTLD patients (≤25 years) following SOT. These 45 paediatric SOT patients (28 heart, 11 liver, six kidney) were diagnosed with PTLD 45 months (mean; SD 43; range 4–153; median 24·5) after SOT, with PTLD diagnosis at 118 months (mean) (SD 77; range 14–287) of age. Of 40 evaluable tumours (11 monomorphic, 19 polymorphic, five early lesions, five rare subtypes), 32 (80%) had detectable EBV and 28 (70%) were classified as CD20+. Patients whose PTLD expressed CD20 or EBV had shorter intervals between SOT and PTLD onset (28 vs. 64 or 77 months for CD20 and EBV respectively) (P < 0·02), even after adjusting for age at SOT. Patients with CD20+ tumours had higher 5‐year PTLD‐related EFS (83·7% vs. 28·6%, P < 0·001) and OS (95·8% vs. 56·3%, P = 0·01). EBV expression was unrelated to PTLD‐related EFS or OS. CD20 expression is associated with timing of development of PTLD and predicts survival in PTLD diagnosed following paediatric SOT.
A reticulum cell sarcoma was diagnosed in a myasthenic patient 14 years after the first manifestations of myasthenia gravis. The association of myasthenia and malignancy, especially lymphoreticular, is discussed in view of an increasing number of similar reports in the literature. It is suggested that autoimmune diseases, myasthenia gravis and malignant processes might have a common underlying abnormal immune state related to thymic pathology.
The risk of developing post transplant lymphoproliferative disease (PTLD) following solid organ transplantation (SOT) in children is in large part dependent on the specific organ transplanted and the degree of immune suppression post SOT (Webber et al Lancet 2006; Dharnidharka et al Transplantation 2001; Newell et al Transplantation 1996). However, the importance of expression of CD20 and/or Epstein-Barr virus (EBV) as prognostic factors for development and survival of pediatric PTLD after SOT in young patients are poorly understood. We previously demonstrated the safety and efficacy of cyclophosphamide, prednisone and rituximab (CPR) in CD20+ PTLD (Orjuela/Cairo, CCR 2005). We now report on our experience in children, adolescents and young adults with PTLD following SOT treated at a single institution from 1990–2008 and on the prognostic significance of expression of CD20 and EBV in this population. 45 SOT pts (28 heart, 11 liver, 6 kidney) were diagnosed with PTLD (53.3 % female) at a mean onset of 45±43 months (mo) post primary SOT (4–153). Three patients had multiple SOT. Age at diagnosis of PTLD ranged from14 to 287 mo with mean 118 (SD=77) mo. EBV and CD20 status were evaluated in all evaluable tumor sites. CD20 status was categorized as positive when all tumor sites expressed CD20 (by IHC) and negative when only some or no tumor sites expressed CD20. EBV status was categorized as positive when any tumor sites were EBV positive (by ISH), and negative when no tumor sites were EBV positive. Of 40 evaluable tumors (11 monomorphic, 19 polymorphic, 5 early lesions, 2 T-cell lymphomas, and 3 rarer types (2 HD, 1 multiple myeloma like), 32 (80%) had detectable EBV, while 28 (70%) were classified as CD20 positive. EBV expression was unrelated to age at SOT. Those patients whose PTLD expressed CD20 and/or EBV had shorter time interval between last SOT and the onset of PTLD (CD20 positive vs negative (mean±SD): 28±31 mo vs 64±44 mo, p<0.01, EBV positive vs negative: 29±24 vs 77±59 mos, p<0.02, Wilcoxon test). After controlling for the age at last SOT in the regression model for the time interval between last SOT and PTLD, expression of either CD20 or EBV was significantly associated with the shorter length of the interval. All patients had immunosuppression reduced, followed by chemo-and immunotherapy as needed. Patients with CD20 positive PTLD had a higher 5-year overall and PTLD related EFS than those patients whose PTLD was CD20 negative (92 vs 56%, p=0.02; 84 vs 29%, p<0.001, Chi-square test). The survival curve for EFS differed by CD20 status, log rank test, p<0.01 (Figure one). Organ transplant type and morphology subtype were unrelated to OS or EFS. There was no significant difference in OS or EFS based on EBV expression. In summary, expression of CD20 and/or EBV in young patients with PTLD post SOT are both important predictors of the length of time that elapses between SOT and development of PTLD. CD20 positive PTLD is associated with significantly improved 5-year OS and EFS for PTLD in young SOT patients. Patients with CD20 negative PTLD appear to have lower 5-year survival and EFS suggesting a need for alternative treatment strategies. Figure Figure
8070 Background: The roles of CD20 and EBV as prognostic features for development and survival of pediatric PTLD after SOT are poorly understood. We previously demonstrated the safety and efficacy of cyclophosphamide, prednisone and rituximab (CPR) in CD20+ PTLD (Orjuela/Cairo, CCR 2005) Methods: All patients (pts), =25 yrs with PTLD in the past 15 yrs were analyzed and classified according to presence of detectable EBV or CD20 by IHC or ISH. Overall survival (OS) and EFS were estimated using Kaplan-Meier, significance was assessed by t-test comparison and Mantel-Cox. Results: 41 SOT pts (28 heart, 8 liver, 4 kidney) had PTLD (53.6% female) at a median of 38.8 months (mo) post SOT (4–43); Age 14–263 mo. Of 35 evaluable tumors, 29 (82.9%) had detectable EBV, while 22 (62.9%) expressed CD20 antigen. All pts had immunosuppression reduced, followed by chemo- and immunotherapy as needed. In pts with =9 mo follow-up after PTLD (n = 38) (median 49 mo, 10–184) OS is 73.2% and PTLD related EFS is 63%. Pts with EBV+ tumors had a shorter time to onset than those with EBV- tumors (median 18 vs 44 mo, p = 0.002). Pts with CD20+ PTLD were diagnosed earlier than those with CD20- PTLD (median 19 vs 62 mo, p= 0.006). PTLD-related 5 yr EFS showed significantly increased survival for CD20+ over CD20- pts (90 ± 6.5% vs 25 ± 11.2%, respectively [95% CI], p = 0.001). EBV status did not have a significant effect on OS (p=0.7) or EFS (p=0.7). Conclusions: CD20 and EBV are important predictors of time to PTLD development and presence of CD20 predicts for significantly improved EFS for SOT PTLD. CD20- PTLD pts appear to have lower EFS suggesting a need for alternative treatment strategies. No significant financial relationships to disclose.
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