TY - JOUR
T1 - Immunosuppression Is Associated with Clinical Features and Relapse Risk of B Cell Posttransplant Lymphoproliferative Disorder
T2 - A Retrospective Analysis Based on the Prospective, International, Multicenter PTLD-1 Trials
AU - Zimmermann, Heiner
AU - Babel, Nina
AU - Dierickx, Daan
AU - Morschhauser, Franck
AU - Mollee, Peter
AU - Zaucha, Jan M.
AU - Dreyling, Martin H.
AU - Dührsen, Ulrich
AU - Reinke, Petra
AU - Verhoef, Gregor
AU - Subklewe, Marion
AU - Hüttmann, Andreas
AU - Tousseyn, Thomas
AU - Bachy, Emmanuel
AU - Hauser, Ingeborg A.
AU - Tarella, Corrado
AU - Van Den Neste, Eric
AU - Gheysens, Olivier
AU - Anagnostopoulos, Ioannis
AU - Leblond, Veronique
AU - Riess, Hanno
AU - Choquet, Sylvain
AU - Trappe, Ralf U.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Background Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors, and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear. Methods This is a retrospective analysis of immunosuppression, patient baseline characteristics, and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by cyclophosphamide (CHOP-21 chemotherapy) 750 mg/m2 intravenously [IV] day (d) 1, doxorubicin 50 mg/m2 IV d1, vincristine 1.4 mg/m2 (maximum, 2 mg) IV d1, and prednisone 50 mg/m2 PO d1-5, every 21 days) or risk-stratified sequential treatment (rituximab followed by rituximab or rituximab (R-CHOP-21 immunochemotherapy) 375 mg/m2 IV day (d) 1, cyclophosphamide 750 mg/m2 IV d1, doxorubicin 50 mg/m2 IV d1, vincristine 1.4 mg/m2 (max. 2 mg) IV d1, and prednisone 50 mg/m2 PO d1-5, every 21 days). Results Patient baseline characteristics at diagnosis of PTLD differed significantly depending on immunosuppression before diagnosis. Compared with immunosuppression before diagnosis, significantly fewer patients received an antimetabolite or a calcineurin inhibitor (CNI) after diagnosis of PTLD. Relapse risk measured as landmark TTP was significantly higher for patients on corticosteroids compared to all others (P = 0.010) as well as for patients on ciclosporin compared with those on tacrolimus (P = 0.002), but similar for those on antimetabolites compared with all others (P = 0.912). In a Cox regression analysis of landmark TTP, corticosteroid-containing immunosuppression after diagnosis of PTLD (P = 0.002; hazard ratio, 11.195) and age (P = 0.001; hazard ratio, 1.076/year) were identified as independent, significant risk factors for PTLD relapse. Conclusions In the prospective PTLD-1 trials, corticosteroid use after diagnosis of PTLD is associated with an increased risk of relapse, whereas the use of antimetabolites is not. These findings require prospective validation.
AB - Background Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors, and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear. Methods This is a retrospective analysis of immunosuppression, patient baseline characteristics, and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by cyclophosphamide (CHOP-21 chemotherapy) 750 mg/m2 intravenously [IV] day (d) 1, doxorubicin 50 mg/m2 IV d1, vincristine 1.4 mg/m2 (maximum, 2 mg) IV d1, and prednisone 50 mg/m2 PO d1-5, every 21 days) or risk-stratified sequential treatment (rituximab followed by rituximab or rituximab (R-CHOP-21 immunochemotherapy) 375 mg/m2 IV day (d) 1, cyclophosphamide 750 mg/m2 IV d1, doxorubicin 50 mg/m2 IV d1, vincristine 1.4 mg/m2 (max. 2 mg) IV d1, and prednisone 50 mg/m2 PO d1-5, every 21 days). Results Patient baseline characteristics at diagnosis of PTLD differed significantly depending on immunosuppression before diagnosis. Compared with immunosuppression before diagnosis, significantly fewer patients received an antimetabolite or a calcineurin inhibitor (CNI) after diagnosis of PTLD. Relapse risk measured as landmark TTP was significantly higher for patients on corticosteroids compared to all others (P = 0.010) as well as for patients on ciclosporin compared with those on tacrolimus (P = 0.002), but similar for those on antimetabolites compared with all others (P = 0.912). In a Cox regression analysis of landmark TTP, corticosteroid-containing immunosuppression after diagnosis of PTLD (P = 0.002; hazard ratio, 11.195) and age (P = 0.001; hazard ratio, 1.076/year) were identified as independent, significant risk factors for PTLD relapse. Conclusions In the prospective PTLD-1 trials, corticosteroid use after diagnosis of PTLD is associated with an increased risk of relapse, whereas the use of antimetabolites is not. These findings require prospective validation.
UR - http://www.scopus.com/inward/record.url?scp=85055154386&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055154386&partnerID=8YFLogxK
U2 - 10.1097/TP.0000000000002269
DO - 10.1097/TP.0000000000002269
M3 - Article
C2 - 29757894
AN - SCOPUS:85055154386
VL - 102
SP - 1914
EP - 1923
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 11
ER -