Immunosuppression Is Associated With Clinical Features and Relapse Risk of B Cell Posttransplant Lymphoproliferative Disorder: A Retrospective Analysis Based on the Prospective, International, Multicenter PTLD-1 Trials.
Abstract | BACKGROUND: 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/m intravenously [IV] day (d) 1, doxorubicin 50 mg/m IV d1, vincristine 1.4 mg/m (maximum, 2 mg) IV d1, and prednisone 50 mg/m PO d1-5, every 21 days) or risk-stratified sequential treatment ( rituximab followed by rituximab or rituximab (R-CHOP-21 immunochemotherapy) 375 mg/m IV day (d) 1, cyclophosphamide 750 mg/m IV d1, doxorubicin 50 mg/m IV d1, vincristine 1.4 mg/m (max. 2 mg) IV d1, and prednisone 50 mg/m 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.
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Authors | Heiner Zimmermann, Nina Babel, Daan Dierickx, Franck Morschhauser, Peter Mollee, Jan M Zaucha, Martin H Dreyling, Ulrich Dührsen, Petra Reinke, Gregor Verhoef, Marion Subklewe, Andreas Hüttmann, Thomas Tousseyn, Emmanuel Bachy, Ingeborg A Hauser, Corrado Tarella, Eric Van Den Neste, Olivier Gheysens, Ioannis Anagnostopoulos, Veronique Leblond, Hanno Riess, Sylvain Choquet, Ralf U Trappe |
Journal | Transplantation
(Transplantation)
Vol. 102
Issue 11
Pg. 1914-1923
(Nov 2018)
ISSN: 1534-6080 [Electronic] United States |
PMID | 29757894
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenal Cortex Hormones
- Antimetabolites
- Calcineurin Inhibitors
- Immunosuppressive Agents
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Topics |
- Adolescent
- Adrenal Cortex Hormones
(administration & dosage, adverse effects)
- Adult
- Aged
- Aged, 80 and over
- Antimetabolites
(administration & dosage, adverse effects)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- B-Lymphocytes
(drug effects, immunology)
- Calcineurin Inhibitors
(administration & dosage, adverse effects)
- Clinical Trials as Topic
- Disease Progression
- Female
- Humans
- Immunosuppressive Agents
(administration & dosage, adverse effects)
- Lymphoproliferative Disorders
(diagnosis, drug therapy, etiology, immunology)
- Male
- Middle Aged
- Multicenter Studies as Topic
- Organ Transplantation
(adverse effects)
- Recurrence
- Retrospective Studies
- Risk Assessment
- Risk Factors
- Time Factors
- Treatment Outcome
- Young Adult
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