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End-of-Treatment Positron Emission Tomography After Uniform First-Line Therapy of B-Cell Posttransplant Lymphoproliferative Disorder Identifies Patients at Low Risk of Relapse in the Prospective German PTLD Registry

Zimmermann, Heiner, MD1,2; Denecke, Timm, MD3; Dreyling, Martin, H., MD4; Franzius, Christiane, MD5,6; Reinke, Petra, MD7; Subklewe, Marion, MD4; Amthauer, Holger, MD8; Kneba, Michael, MD, PhD2; Riess, Hanno, MD9; Trappe, Ralf, U., MD1,2,9

doi: 10.1097/TP.0000000000002006
Original Clinical Science—General

Background Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end-of-treatment (EOT) PET has only been addressed in small case series.

Methods We performed a retrospective, multicenter study of 37 patients with CD20-positive PTLD after solid organ transplantation treated with uniform, up-to-date, first-line protocols in the prospective German PTLD registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive.

Results By computed tomography (CT) final staging, 18 of 37 patients had a complete response, 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24 of 37 patients and positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD relapse was 38%, and the negative predictive value was 92%. Time to progression (TTP) and progression-free-survival were significantly longer in the PET negative group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (P = 0.001), time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT PET.

Conclusions Even without baseline imaging, EOT PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.

Posttransplant lymphoproliferative disorder (PTLD) can be detected by fluorine-18 fluorodeoxyglucose-positronemission tomography (PET) and end of treatment PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.

1 Department of Hematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Bremen, Germany.

2 Department of Internal Medicine II: Hematology and Oncology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.

3 Klinik für Strahlenheilkunde, Charité-Universitätsmedizin Berlin, Berlin, Germany.

4 Department of Internal Medicine III, University of Munich, Munich, Germany.

5 Zentrum für Nuklearmedizin und PET/CT, Bremen, Germany.

6 Zentrum für modern Diagnostik (ZEMODI), Bremen, Germany.

7 Department of Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.

8 Department of Nuclear Medicine, Section Clinical Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.

9 Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Received 29 June 2017. Revision received 28 September 2017.

Accepted 12 October 2017.

This study was supported by Bremer Krebsgesellschaft e.V. through a research grant to HZ.

H.Z. reports institutional grants form Roche, and nonfinancial support from Celgene and Roche, outside the submitted work. T.D. reports personal fees and grants from Bayer, Siemens, Toshiba, General Electric, b.e. imaging, Roche, Parexel, GE, IPSEN Pharma, Guerbet, and Novartis outside the submitted work. M.H.D. reports institutional grants and personal fees from Roche, outside the submitted work. P.R. reports personal fees or travel support from Teva, Thermo Fisher, Pfizer, Astellas, Amgen, Baxalta, MSD, Pluristem, and Novartis, outside the submitted work. M.S. reports institutional grants from Roche, Amgen and OBT and personal fees or travel support from Amgen, Pfizer, Seattle Genetics, Gilead and Celgene, outside the submitted work. H.A. reports grants and personal fees from Siemens Healthcare, Covidien, GE Healthcare and Sirtex Medical. M.K. reports institutional grants and personal fees from Roche, outside the submitted work. H.R. reports personal fees or travel support from Aspen, Bayer, Boehringer Ingelheim, Celgene, Pfizer and Roche, outside the submitted work. R.U.T. reports grants from Hoffmann-La Roche, Amgen, and Chugai France; grants, personal fees and nonfinancial support from Hoffmann-La Roche and Novartis, grants and personal fees from CSL Behring, personal fees from Abbvie, grants from Mundipharma, nonfinancial support from Celgene, Takeda, Leo Pharma and Gilead all outside the submitted work. All other authors declared no conflicts of interest.

H.Z. and R.U.T. designed the study. R.U.T. is the principal investigator and takes primary responsibility for the article. M.D., P.R., M.S., M.K., and H.R. recruited significant numbers of patients. T.D., C.F., and H.A. performed and reported significant number of PET scans. T.D. and H.A. performed a central review of PET scans. H.Z. and R.U.T. collected, analyzed, and interpreted the data. H.Z., T.D., C.F., and R.U.T. wrote the article. All authors had full access to the final version of the article and agreed to publication.

Correspondence: Ralf Ulrich Trappe, MD, DIAKO Ev. Diakonie-Krankenhaus Bremen, Department of Internal Medicine II: Hematology and Oncology, Gröpelinger Heerstr. 406-408, 28239 Bremen, Germany. (rtrappe@gwdg.de.).

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