Cerebellum/liver index on baseline 18F-FDG PET/CT to improve prognostication in post-transplant lymphoproliferative disorders: a multicenter retrospective study
David MorlandLukshe KanagaratnamF. HubeléElise ToussaintSylvain ChoquetAurélie KasPierre-Ambroise CaquotCorinne HaïounEmmanuel IttiStéphane LeprêtrePierre DecazesFontanet BijouPaul M. SchwartzCaroline JacquetAdrien ChauchetJ MatuszakNassim KamarPierre PayouxLoïc RenaudLaëtitia VercellinoJérôme PaillassaPacôme FosseMorgane CheminantJ.M. CorréasRoch HouotXavier PalardMarie Le CannMaria-Angéla Castilla-LièvreYann GuillerminHaïfa BahriÉric Durot
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Abstract Background Besides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses. Results A total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0–4.0) and 2.4 (1.3–4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 ( p = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS. Conclusion CLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.Keywords:
Lymphoproliferative Disorders
International Prognostic Index
Post-transplant lymphoproliferative disorder
The International Prognostic Index (IPI) is a clinical prognostic tool used for more than 20 years in the risk stratification of patients with de novo diffuse large B cell lymphoma (DLBCL) who rece...
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Lymphoproliferative disorders are one of the most common malignancies in recipients of solid organ and bone marrow transplantation, developing in approximately 2% of patients. This chapter talks about the clinical features, histopathology, immunophenotype, molecular genetics, treatment, and prognosis of cutaneous post-transplant lymphoproliferative disorders. Post-transplant lymphoproliferative disorders are classified according to four major categories: (i) early lesions (reactive plasmacytic hyperplasia, infectious mononucleosis-like lesions); (ii) polymorphic post-transplant lymphoproliferative disorder; (iii) monomorphic post-transplant lymphoproliferative disorder, with clinicopathologic features corresponding to "conventional" entities of B- and NK/T-cell lymphomas; and (iv) classical Hodgkin lymphoma-type post-transplant lymphoproliferative disorder. The chapter also presents a short résumé of cutaneous post-transplant lymphoproliferative disorders.
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Cutaneous diffuse large B-cell lymphoma, leg type, is a malignant lymphoma of intermediate behavior, occurring mostly on leg(s) of elderly patients. This chapter describes the clinical features, histopathology, immunophenotype, molecular genetics, treatment and prognosis of diffuse large B-cell lymphoma, leg type. It is a matter of discussion whether diffuse large B-cell lymphoma, leg type, is a specific entity per se, or does simply represent a primary cutaneous variant of diffuse large B-cell lymphoma, unspecified. In fact, there are more similarities than differences between these groups, and it has been suggested that diffuse large B-cell lymphoma, leg type, should not be considered as a separate entity, but rather classified within the group of diffuse large B-cell lymphoma, unspecified. It must be remembered that diagnosis of cutaneous diffuse large B-cell lymphoma, leg type, is made only upon negative staging investigations, as any extracutaneous diffuse large B-cell lymphoma may involve the skin secondarily.
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The International Prognostic Index (IPI) has been a powerful tool for predicting post-treatment outcomes and comparing results across clinical trials in diffuse large B-cell lymphoma (DLBCL) for more than 20 years. Given that rituximab has improved survival across all risk groups since the late 1990s, investigators have created a new prognostic model based on a retrospective analysis of 1650 newly diagnosed DLBCL patients who received induction rituximab-based chemotherapy from 2000 to 2010 at seven centers in the National …
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The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20 years. The utility of the IPI must be reassessed in the era of immunochemotherapy. Seven risk factors at diagnosis were identified, and a maximum of 7 points were assigned to each patient. Four risk groups were created: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the rituximab era, we performed a retrospective analysis of patients with DLBCL treated with R-CHOP and built an biological markers adjusted IPI with the goal of improving risk stratification.Clinical features from 60 adults with de novo DLBCL diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI remains predictive, but it cannot identify the high-risk subgroup. Compared with the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4 year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is more powerful than the IPI for helping guide treatment planning and interpretation of clinical trials.
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Epstein-Barr virus (EBV) is known to be involved in the majority of patients who develop post-transplant lymphoproliferative disorder after solid organ transplant. We conducted a retrospective study to determine the utility of qualitative and quantitative Epstein-Barr virus polymerase chain reaction (PCR) for the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients. Peripheral blood leukocytes obtained from 35 adult solid organ transplant patients consecutively referred for evaluation of possible post-transplant lymphoproliferative disorder, were tested by EBV PCR at the time of initial evaluation and at time points thereafter. Eighteen of 35 (51%) patients were ultimately diagnosed with post-transplant lymphoproliferative disorder by tissue biopsy. Fifteen of 18 (83%) patients were found to have EBER-1 positive tumors by in situ hybridization. EBV PCR was positive in 7 of 15 patients, suggesting a sensitivity of 39%. Seventeen patients without post-transplant lymphoproliferative disorder and three with EBER-1 negative post-transplant lymphoproliferative disorder all had negative EBV PCR tests, suggesting a specificity of 100%. We observed that declines in EBV DNA load were associated with response to therapeutic interventions, such as reduction in immunosuppression, rituximab therapy and chemotherapy. We conclude that peripheral blood EBV PCR may have a role in the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients. Epstein-Barr virus (EBV) is known to be involved in the majority of patients who develop post-transplant lymphoproliferative disorder after solid organ transplant. We conducted a retrospective study to determine the utility of qualitative and quantitative Epstein-Barr virus polymerase chain reaction (PCR) for the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients. Peripheral blood leukocytes obtained from 35 adult solid organ transplant patients consecutively referred for evaluation of possible post-transplant lymphoproliferative disorder, were tested by EBV PCR at the time of initial evaluation and at time points thereafter. Eighteen of 35 (51%) patients were ultimately diagnosed with post-transplant lymphoproliferative disorder by tissue biopsy. Fifteen of 18 (83%) patients were found to have EBER-1 positive tumors by in situ hybridization. EBV PCR was positive in 7 of 15 patients, suggesting a sensitivity of 39%. Seventeen patients without post-transplant lymphoproliferative disorder and three with EBER-1 negative post-transplant lymphoproliferative disorder all had negative EBV PCR tests, suggesting a specificity of 100%. We observed that declines in EBV DNA load were associated with response to therapeutic interventions, such as reduction in immunosuppression, rituximab therapy and chemotherapy. We conclude that peripheral blood EBV PCR may have a role in the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients.
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Despite advances in therapy, still up to one third of patients with diffuse large B-cell lymphoma (DLBCL) will ultimately die of their disease. The revised international prognostic index (R-IPI) is...
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