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Aim: Our aim was (1) to evaluate the prevalence of steatosis in lymphoma patients and its evolution during treatment; (2) to evaluate the impact of hepatic steatosis on 18F-FDG liver uptake; and (3) to study how hepatic steatosis affects the Deauville score (DS) for discriminating between responders and non-responders.Methods: Over a 1-year period, 358 PET scans from 227 patients [122 diffuse large B cell lymphoma (DLBCL), 57 Hodgkin lymphoma (HL) and 48 Follicular lymphoma (FL)] referred for baseline (n = 143), interim (n = 79) and end-of-treatment (EoT, n = 136) PET scans were reviewed. Steatosis was diagnosed on the unenhanced CT part of PET/CT examinations using a cut-off value of 42 Hounsfield units (HU). EARL-compliant SULmax were recorded on the liver and the tumour target lesion. DS were then computed.Results: Prevalence of steatosis at baseline, interim and EoT PET was 15/143 (10.5%), 6/79 (7.6%) and 16/136 (11.8%), respectively (p = 0.62).Ten out of 27 steatotic patients (37.0%) displayed a steatotic liver on all examinations. Six patients (22.2%) had a disappearance of hepatic steatosis during their time-course of treatment. Only one patient developed steatosis during his course of treatment. Liver SULmax values were significantly lower in the steatosis versus non-steatotic groups of patients for interim (1.66 ± 0.36 versus 2.15 ± 0.27) and EoT (1.67 ± 0.29 versus 2.17 ± 0.30) PET. CT density was found to be an independent factor that correlated with liver SULmax, while BMI, blood glucose level and the type of chemotherapy regimen were not. Using a method based on this correlation to correct liver SULmax, all DS4 steatotic patients on interim (n = 1) and EoT (n = 2) PET moved to DS3.Conclusions: Steatosis is actually a theoretical but not practical issue in most patients but should be recognised and corrected in appropriate cases, namely, for those patients scored DS4 with a percentage difference between the target lesion and the liver background lower than 30%. [ABSTRACT FROM AUTHOR]

Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1+T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1+T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1+T cells of patients or HSs mostly exhibited a naïve phenotype, the majority of tumor Vδ1+T cells showed a central memory phenotype. Resident or circulating γδ T cells from patients were not functionally impaired since they produced high levels of IFN-γ. Collectively, our findings are in favor of γδ T cell activation in tumors and open new perspectives for their modulation in DLBCL immunotherapy. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that excessive blood transfusion may be associated with impaired survival or cardiovascular events. One way to reduce the number of red blood cells (RBCs) is to transfuse 1 unit (1RBC) instead of 2 units of RBCs (2RBC).Study Design and Methods: Patients requiring blood transfusions in hematologic intensive care unit were included in a prospective study using a single RBC unit per transfusion and were compared with an historical cohort who received 2 RBC units per transfusion.Results: A total of 1323 units were transfused to 126 patients between 2013 and 2014. The 186 patients in the comparative cohort received a total of 1824 RBC units in a 2-RBC-unit policy between 2010 and 2012. The mean number of units was 7.35 (SD, 5.9 units; 95% confidence interval [CI], 6.5-8.2 units) in the 1RBC group and 8.14 units (SD, 6.2 units; 95% CI, 7.3-8.9 units) in the 2RBC group. The absolute mean difference was -0.79 (95% CI, -1.98 to 0.40; p = 0.09). In the 1RBC allogeneic hematopoietic stem cell transplantation (allo-HSCT) subgroup, a significant reduction in the number of RBC units transfused was observed in comparison with the historical 2RBC allo-HSCT group (5 units vs. 7.7 units; p = 0.01). No anemia-related side effects were reported. Overall survival did not differ between the two groups.Conclusion: The 1RBC transfusion policy made is feasible in patients with transient hematologic toxicity after chemotherapy. The number of units transfused between the two groups was not different. However, in the allo-HSCT group, the use of a single RBC unit reduced significantly RBC consumption. A randomized trial comparing the two strategies is planned with a medicoeconomic evaluation. [ABSTRACT FROM AUTHOR]

Aims: (1) To perform a comprehensive analysis of the time elapsed between the last G-CSF injection and the PET/CT examination on the biodistribution of 18F-FDG, with emphasis on liver, spleen, and bone marrow uptake, and (2) to investigate whether an inversion of the liver to spleen ratio affects the Deauville scoring. Materials and methods: Retrospectively included were 74 consecutive diffuse large B cell lymphoma (DLBCL) patients referred for baseline and interim examinations and receiving immunochemotherapy with various G-CSF regimens. A comprehensive evaluation considering baseline metabolic active tumour volume (MATV), factors affecting liver uptake, the type of G-CSF, and the time elapsed between chemotherapy/G-CSF and interim PET/CTs was performed. Results: Mean (± SD) percentage variations between baseline and interim PET/CTs (i-PET/CT) for bone marrow (%Variation_BONE), liver (%Variation_LIVER) and spleen (%Variation_SPLEEN) were equal to 32.0 ± 46.9%, 16.1 ± 42.8%, and 10.6 ± 51.1 %, respectively. %Variation_LIVER and %Variation_SPLEEN were higher in patients using lenograstim, but this was linked to lower uptakes at baseline and was therefore likely not due to G-CSF itself. The mean delay between G-CSF injection and i-PET/CT acquisition was not an independent explanatory variable for %Variation_BONE, %Variation_LIVER, and %Variation_SPLEEN. On the contrary, %Variation_BONE and %Variation_SPLEEN were negatively correlated to the time-lapse between the end of chemotherapy and i-PET/CT: ρ = − 0.342 (p = 0.010) and ρ = − 0.529 (p < 0.0001), respectively. Patients with a time-lapse since the last injection of chemotherapy < 17 days displayed higher bone and spleen SUVmaxEARL. %Variation_LIVER was positively correlated to baseline MATV: ρ = 0.243 (p = 0.039). Patients displaying a high baseline MATV ≥ 177 cc had significantly lower liver SUVmaxEARL at baseline. This difference was no longer observed at i-PET/CT, after tumours had shrunk. Conclusions: Neither the type of G-CSF used nor the time elapsed between its last injection and i-PET/CT examination independently influences bone, hepatic, or splenic uptakes at i-PET/CT. The major determinant for the occurrence of a bone or spleen hypermetabolism on i-PET/CT is the time elapsed between the chemotherapy and the examination, which should be maintained above 15 days. Inversion of the liver to spleen ratio appeared to be due to increased spleen hypermetabolism on i-PET/CT, making unlikely an impact on the Deauville scoring. [ABSTRACT FROM AUTHOR]

In DLBCL, the Deauville scoring system (DS) is the standard for PET/CT response assessment. An alternative system, based on the semi-quantitative change in standardized uptake values, namely ΔSUVmax, has been reported to be more objective than the DS. We aimed to compare ΔSUVmax and DS for risk stratification of DLBCL patients on end-of-treatment (EoT) PET. 108 consecutive patients were included. 2-year EFS Kaplan-Meier survival analyses and Cox regression models were performed. 2-year EFS was significantly different between favorable ΔSUVmax (favΔ < -86.5%) and unfavorable ΔSUVmax (unfavΔ ≥ -86.5%) patients: 100.0% ± 0.0 versus 58.3% ± 14.2 ( p  = 0.001). On Cox multivariable regression, ΔSUVmax status was the only independent predictor of 2-year EFS, outperforming DS. Therefore, ΔSUVmax should be computed for non-responder patients, especially DS4, as the 2-year EFS is not different between responders and non-responders in the case of favΔ. Further studies are needed in order to confirm this hypothesis.

This was the first-in-humans clinical study of 18 F-fludarabine, which is a radiopharmaceutical for PET imaging in lymphoma, for which many issues remain controversial with the standard radiotracer 18 F-FDG. Methods: 18 F-fludarabine PET or PET/CT was performed on 10 patients: 5 with diffuse large B-cell lymphoma (DLBCL) and 5 with chronic lymphocytic leukemia. The tumor uptake, biodistribution, and radiation dosimetry of 18 F-fludarabine were evaluated. Six successive partial-body PET scans were acquired for 250 min after an intravenous 4 MBq/kg bolus of 18 F-fludarabine. SUVs were recorded for each involved lymph node territory and for several extranodal sites, with particular reference to the liver. To assess the time-related uptake profile of 18 F-fludarabine, PET images were analyzed by delineating volumes of interest over the uptake sites on the optimal scan for visual observation and were projected onto all coregistered scans of the same subject. Physical examination, laboratory studies, and contrast-enhanced CT were performed on all patients. For the DLBCL group, 18 F-FDG PET was also considered. Results: In DLBCL patients, increased 18 F-fludarabine uptake was observed in sites considered abnormal by CT or 18 F-FDG, with SUVs significantly higher in involved lesions than in physiologic nontarget sites. Nonetheless, the comparison of 18 F-fludarabine and 18 F-FDG PET showed discrepancies in 2 patients. In chronic lymphocytic leukemia patients, the uptake of 18 F-fludarabine coincided with sites expected to be involved (including splenic invasion) according to conventional clinical and CT staging and was significant in hematopoietic bone marrow. No uptake was observed, whatever the disease group, in cardiac muscle or brain. The mean effective dose from a mean injected 18 F-fludarabine activity of 305 ± 76 MBq was 3.07 ± 0.81 mSv. Conclusion: 18 F-fludarabine PET might well be a promising tool for lymphoproliferative diseases. The radiation dose of this radiopharmaceutical is below that of 18 F-FDG. The specificity of this PET probe for lymphoid cells, its absence of accumulation in reactive tissues, and its feasibility for detection of bone marrow infiltration might play an innovative role in lymphoma imaging., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation (allo-HCT) is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allo-HCT for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript reports on general considerations regarding allo-HCT for lymphoma and elaborates on the use of alternative donors in this setting., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic haematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript specifically reports on our conclusions regarding Hodgkin's lymphoma as well as rarer entities, such as T cell lymphomas., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This paper specifically reports on our conclusions regarding indolent lymphomas, mainly follicular lymphoma and chronic lymphocytic leukemia., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly in the case of after autologous stem cell transplantation if remission can be achieved. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This section specifically reports on our conclusions regarding diffuse large B cell lymphoma., (Copyright © 2017. Published by Elsevier Masson SAS.)

Peripheral T-cell lymphoma (PTCL) is a group of diseases with poor outcome and few therapeutic options. We aimed to assess the efficacy of bendamustine in real life cohort of patients.Between November 2009 and March 2015, 138 PTCL patients were treated with bendamustine in 27 centers. Population median age was 64 (28-89) years with male/female ratio of 1.4. There were mainly angio-immunoblastic (AITL = 71), PTCL-not otherwise specified (PTCL-NOS = 40) and anaplastic large cell lymphoma (ALCL = 8). The majority of patients (96%) had disseminated disease and extranodal localizations (77%). Median number of chemotherapy lines prior to bendamustine was 2 (1-8). Median duration of response (DoR) after the last chemotherapy prior to bendamustine was 4.3 months (1-70) and 50% of patients had refractory disease.Median number of administered bendamustine cycles was 2 (1-8) and 72 patients (52%) received less than 3 mostly because of disease progression. Median dose was 90 (50-150) mg/m². Overall response rate (ORR) was 32.6% with complete response (CR) rate of 24.6% and median DoR was 3.3 months (1-39). AITL patients were more sensitive than PTCL-NOS patients (ORR: 45.1 versus 20%, p = 0.01). Median PFS and OS were 3.1 (0.2-46.3) and 4.4 (0.2-55.4) months. On multivariate analysis, refractory disease (p = 0.001) and extranodal localization (p = 0.028) adversely influenced ORR. Grade 3-4 thrombocytopenia, neutropenia and infections were reported in 22, 17 and 23% of cases respectively.Bendamustine as single agent could be considered as a therapeutic option for relapsed or refractory PTCL, particularly in chemosensitive or AITL patients. Combinations of bendamustine with other drugs warrant further evaluation.

The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23-85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n = 54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1-5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42 ± 7% and 44 ± 7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P = 0.008) and (P = 0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07-0.67)] and progression-free survival [HR = 0.17 (0.05-0.54)]). In conclusion, non-Hodgkin lymphoma prognosis with concomitant systemic and neurological involvement at diagnosis is poor with a high risk of relapse when treated with conventional chemotherapies alone. This retrospective study supports the feasibility and the potential benefit of a consolidative strategy with high-dose therapy followed by autologous stem cell transplantation in this subset of patients. This strategy and the best intensive chemotherapy regimen remain to be validated in prospective trials., (Copyright© Ferrata Storti Foundation.)