Post-transplant lymphoproliferative disorders (PTLD) develop in the setting of immunosuppression following solid organ transplant or allogeneic stem cell transplant (alloSCT). Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (‘PTLD-like’) can occur with the use of immunosuppressive agents for autoimmune or related disorders. The optimal first-line treatment and risk stratification tool for PTLD remains unclear and rituximab (R) monotherapy is often used following a reduction of immunosuppression (RIS), reserving combination chemotherapy for those failing this initial approach. However, this approach may not be suitable in those with high risk disease. The aim of this study was to review the outcome of patients with PTLD and PTLD-like disease,
Using the British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database, all patients diagnosed with PTLD and PTLD-like conditions from 1981-2013 were identified, excluding primary CNS lymphoma, low-grade lymphomas and HIV associated lymphomas.
104 patients were identified: 86 PTLD and 18 PTLD-like. PTLD: Median age 47 y (range 6-71); 64% male; 60% late onset (> 1 year from transplant); 71% extranodal (EN) disease; 14% graft involved; 49% elevated LDH (n=36, missing n=13); 59% PS > 2 (n=45, missing n=10); 60% prior renal transplant. Pathology: 57% EBV positive (n=43, missing n=11); 2% early lesions, 13% polymorphic, 79% monomorphic (83% DLBCL), 1.1% classical Hodgkin lymphoma (CHL) and 4.7% unknown. All patients underwent initial RIS, followed by: observation (n=23, 27%), single agent rituximab (n=37, 43%), anthracycline based combination chemotherapy + R (n= 9 (n=6 + R), 10%), single agent chemotherapy + R (n=8 (n=4 + R), 9%); 4 (5%) were too frail to treat. With a median follow-up for living patients of 4.0 y (range 0.8-16.2 y), the 3-y OS and 3-y TTP were 50% and 48%, respectively. Polymorphic cases had a more favorable outcome compared to monomorphic cases with a 3-y OS of 91% vs. 45% (p=0.029) and a 3-y TTP of 73% vs. 44% (p=0.037). Monomorphic PTLD prognostic factors (n=63): In univariate analysis for TTP, an elevated LDH (p=0.006), poor PS >2 (p=.0012), EN sites > 1 (p=0.005), B symptoms (p=0.0019) and GI (p=0.022), kidney (p=0.009) and hepatic (p<0.00001) involvement were all associated with an inferior TTP. Similarly, elevated LDH (p= 0.028), poor PS (p=0.0001) and kidney involvement (p=0.027) were associated with a poor OS. A high IPI score was associated with an inferior outcome: 3-y OS and 3-y TTP for low (0,1) (n=20), intermediate (2,3) (n=34) and high risk (4,5) (n=14) groups were 69%, 40%, and 21% (p=0.03) and 83%, 28%, and 14% (p<0.0001), respectively. For monomorphic DLBCL cases receiving single agent rituximab (n=29), a higher IPI was also associated with a worse 3-y OS (76%, 64%, and 20%, p=0.018) and 3-y TTP (67%, 27%, and 20%, p=0.03) for the low, intermediate and high risk groups, respectively. PTLD-like: Median age 63 y (range 26-74); 50% male; 51% EN disease; 33% LDH elevated (n=6); 44% PS > 2 (n=7, missing n=2); 92% EBV positive (n= 12, missing n=5). Pathology: 1 polymorphic (6%); 15 monomorphic (83%) (DLBCL n=11, 73%, DLBCL/CHL grey zone lymphoma n=2, 13%), 1 CHL (6%), 1 Hodgkin-like (6%), 1 unknown (6%). The majority of patients had a history of rheumatoid arthritis (n=10, 56%) and had been on treatment with methotrexate (n=10, 56%). The median time from onset of autoimmune disorder to the development of PTLD-like disease was 11 y (0.16-50) and the median duration of drug exposure prior to the development of the PTLD-like disease was 5 y (0.16-15y). All patients underwent RIS, followed by observation (n=6, 32%); single agent rituximab (n=4, 21%); anthracycline based combination chemotherapy + R (n=6, 37%; R, n=4); or single agent chemotherapy + R (n=1, 5.3%); 1 was too frail. With a median follow-up of 4.9 y (range 0.3-17 y), the 3-y TTP and OS were 65% and 77%, respectively.
For PTLD, a select group of patients with a low IPI score appear to have high cure rates with single agent rituximab. For those with multiple IPI factors a risk-adapted strategy with earlier use of chemotherapy may be preferred. In the group with PTLD-like disease we observed Hodgkin lymphoma and Hodgkin-like proliferations but also grey zone lymphomas, the latter of which has not been previously reported. Patients with PTLD-like disorders have a more favorable outcome than those with PTLD.
Klasa:Roche Canada: Research Funding. Sehn:Roche/ Genentech: Consultancy, Honoraria, Research Funding. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding. Shenkier:Roche Canada: Research Funding. Connors:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Savage:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding.
Asterisk with author names denotes non-ASH members.