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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Data on venous thromboembolic events (VTEs) in patients receiving immune checkpoint inhibitors (ICIs) are scarce and conflicting. This study investigated the risk of reporting VTEs associated with ICIs in comparison with all other anticancer drugs. The World Health Organization pharmacovigilance database (VigiBase), comprising30 million individual case safety reports, was queried. All reports on patients with cancer, involving at least one anticancer drug as a suspect or interacting drug and registered from January 1, 2008, to May 31, 2021, were included. The association between ICIs and the risk of reporting VTEs was estimated using the reporting odds ratio (ROR) as a measure of disproportionality with all other anticancer drugs as comparators. RORs were estimated as crude and adjusted RORs for age, sex, and other medications (excluding anticancer drugs) associated with risk of VTEs. Among 1,196 patients experiencing VTEs after ICI treatment, the median age was 65 years and 57.6% were men. Anti-PD-1 agents (62.5%) were the most frequently reported. ICIs were not associated with higher reporting of VTEs when compared with other anticancer drugs (crude ROR 0.63, 95% confidence interval (CI) 0.60 to 0.67 and adjusted ROR 0.70, 95% CI 0.65-0.74). No signal of disproportionate reporting was found when considering each class of ICIs. In conclusion, ICIs were not associated with higher reporting of VTEs, in comparison with all other anticancer drugs in a large-scale pharmacovigilance database. Owing to the limitations inherent to pharmacovigilance studies, prospective studies, including an adequate comparison group, are needed to assess the risk of VTEs in ICI-treated patients.

Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974

Two randomised trials (ASTIS, SCOT) of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) versus monthly Cyclophosphamide for severe Systemic Sclerosis (SSc) patients used similar inclusion criteria, but different primary endpoints: event-free-survival (EFS) at 24 months in ASTIS versus the global rank composite score (GRCS) at 54 months in SCOT. Here we analysed the French ASTIS cohort (n = 49) outcome using the same GRCS endpoint as reported in SCOT. All patients, randomised to AHSCT (n = 26) or Cyclophosphamide (n = 23), were evaluated for the non-parametric GRCS endpoint based on: death, EFS, forced vital capacity (FVC), Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 60 months. Secondary endpoints were: EFS, overall survival (OS), HAQ DI and organ status. In intention-to-treat analysis, the GRCS demonstrated superiority for AHSCT (median: 9 versus -19, p = 0.018), mRSS (Δ mRSS: -16 versus -9, p = 0.02), and HAQ-DI (ΔHAQ-DI: -0.89 versus -0.2, p = 0.05) with no significant difference in OS, EFS, lung, heart and kidney function between the groups. In conclusion, this study demonstrates long term benefits of non-myeloablative AHSCT when assessed by the five longitudinal measures within GRCS affording direct primary endpoint comparison between ASTIS and SCOT.

Objectives GCA is a large vessel vasculitis for which triggering factors remain unknown. Clonal haematopoiesis (CH) was associated with atherosclerosis through the induction of inflammation in myeloid cells, and data suggest that CH expansion and inflammation may support each other to induce a pro-inflammatory loop. Our objective was to describe the impact of JAK2p.V617F-mutated myeloproliferative neoplasms (MPNs) on GCA and to screen MPN-free patients for CH mutations. Methods We performed a retrospective case–control study comparing the characteristics of 21 GCA patients with MPN and 42 age- and gender-matched GCA patients without MPN. Also, 18 GCA patients were screened for CH through next-generation sequencing (NGS). Results The most frequent associated MPN was essential thrombocythaemia (ET; n = 11). Compared with controls, GCA patients with MPN had less-frequent cephalic symptoms (71.4 vs 97.6%; P = 0.004) and higher platelet counts at baseline [485 × 109/l (interquartile range 346–586) vs 346 (296–418); P = 0.02]. There was no difference between groups for other clinical features. Overall survival was significantly shorter in patients with MPN compared with controls [hazard ratio 8.2 (95% CI 1.2, 56.6); P = 0.03]. Finally, screening for CH using NGS in 15 GCA patients without MPN revealed CH in 33%. Conclusion GCA patients with MPN display higher platelet counts and shorter overall survival than controls. This association is not fortuitous, given the possible pathophysiological relationship between the two diseases. CH was found in one-third of GCA patients, which may be higher than the expected prevalence for a similar age, and should be confirmed in a larger cohort.

Second primary diffuse large B cell lymphoma (spDLBCL) is defined as a metachronous tumor occurring after a first primary cancer. To date, while R-CHOP is the standard first-line treatment for de novo DLBCL, no available data show that R-CHOP is the optimal treatment for spDLBCL. This exploratory study aimed to investigate treatment of spDLBCL. From 2008 to 2015, the Poitou-Charentes general cancer registry recorded 68 cases of spDLBCL ≤ 80 years old, having received a first-line treatment with either R-CHOP (78%) or other regimens (22%). Patients without R-CHOP have worse overall survival in univariate (HR 2.89 [1.33–6.24], P = 0.007) and multivariate (HR 2.98 [1.34–6.67], P = 0.008) analyses. Patients without R-CHOP more frequently had PS > 1 (67% vs. 28%, P = 0.007) and prior chemotherapy (60% vs. 26%, P = 0.02), which suggests that both of these factors influence a clinician’s decision to not use R-CHOP. Prior chemotherapy had no prognostic impact in univariate and multivariate analyses; this result could call into question the risk-benefit balance of not using R-CHOP to prevent toxicity. In our study, one DLBCL out of ten occurred after a first primary cancer, and as regards de novo DLBCL, R-CHOP appeared to be the best first-line treatment. Larger series are needed to confirm these results.

Summary Background The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea, the standard therapy for patients with polycythaemia vera, over 3 years of treatment. Methods PROUD-PV and its extension study, CONTINUATION-PV, were phase 3, randomised, controlled, open-label, trials done in 48 clinics in Europe. Patients were eligible if 18 years or older with early stage polycythaemia vera (no history of cytoreductive treatment or less than 3 years of previous hydroxyurea treatment) diagnosed by WHO's 2008 criteria. Patients were randomly assigned 1:1 to ropeginterferon alfa-2b (subcutaneously every 2 weeks, starting at 100 μg) or hydroxyurea (orally starting at 500 mg/day). After 1 year, patients could opt to enter the extension part of the trial, CONTINUATION-PV. The primary endpoint in PROUD-PV was non-inferiority of ropeginterferon alfa-2b versus hydroxyurea regarding complete haematological response with normal spleen size (longitudinal diameter of ≤12 cm for women and ≤13 cm for men) at 12 months; in CONTINUATION-PV, the coprimary endpoints were complete haematological response with normalisation of spleen size and with improved disease burden (ie, splenomegaly, microvascular disturbances, pruritus, and headache). We present the final results of PROUD-PV and an interim analysis at 36 months of the CONTINUATION-PV study (per statistical analysis plan). Analyses for safety and efficacy were per-protocol. The trials were registered on EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357-17 (CONTINUATION-PV, which is ongoing). Findings Patients were recruited from Sept 17, 2013 to March 13, 2015 with 306 enrolled. 257 patients were randomly assigned, 127 were treated in each group (three patients withdrew consent in the hydroxyurea group), and 171 rolled over to the CONTINUATION-PV trial. Median follow-up was 182·1 weeks (IQR 166·3–201·7) in the ropeginterferon alfa-2b and 164·5 weeks (144·4–169·3) in the standard therapy group. In PROUD-PV, 26 (21%) of 122 patients in the ropeginterferon alfa-2b group and 34 (28%) of 123 patients in the standard therapy group met the composite primary endpoint of complete haematological response with normal spleen size. In CONTINUATION-PV, complete haematological response with improved disease burden was met in 50 (53%) of 95 patients in the ropeginterferon alfa-2b group versus 28 (38%) of 74 patients in the hydroxyurea group, p=0·044 at 36 months. Complete haematological response without the spleen criterion in the ropeginterferon alfa-2b group versus standard therapy group were: 53 (43%) of 123 patients versus 57 (46%) of 125 patients, p=0·63 at 12 months (PROUD-PV), and 67 (71%) of 95 patients versus 38 (51%) of 74 patients, p=0·012 at 36 months (CONTINUATION-PV). The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (seven [6%] of 127 patients) and increased alanine aminotransferase (four [3%] of 127 patients) in the ropeginterferon alfa-2b group, and leucopenia (six [5%] of 127 patients) and thrombocytopenia (five [4%] of 127 patients) in the standard therapy group. Treatment-related serious adverse events occurred in three (2%) of 127 patients in the ropeginterferon alfa-2b group and five (4%) of 127 patients in the hydroxyurea group. One treatment-related death was reported in the standard therapy group (acute leukaemia). Interpretation In patients with early polycythaemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months. However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months. Considering the high and durable haematological and molecular responses and its good tolerability, ropeginterferon alfa-2b offers a valuable and safe long-term treatment option with features distinct from hydroxyurea. Funding AOP Orphan Pharmaceuticals AG.

Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat patients with highly active multiple sclerosis (MS) refractory to disease-modifying therapy. Briefly, cyclophosphamide and filgrastim are used to mobilize autologous hematopoietic stem cells (HSC) into the circulation. HSC are harvested by leukapheresis, purified using a CD34 immunomagnetic selection process, and cryopreserved. Busulphan, cyclophosphamide, and rabbit anti-thymocyte globulin are used to destroy the patient's autoreactive immune system, followed by infusion of the previously collected HSC, which reconstitute a naïve and self-tolerant immune system. Many MS patients experience durable remissions with no evidence of new disease activity following aHSCT. Treatment-related toxicity is rare, but potentially life-threatening complications necessitate appropriate patient selection by MS neurologists and HSCT physicians. AHSCT must be performed with a highly trained multidisciplinary team expert to minimize morbidity and mortality. We present the current aHSCT procedure for an MS indication at The Ottawa Hospital, developed from our program's 20-year experience. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Candidate selection Basic Protocol 2: Autologous hematopoietic stem cell mobilization, collection, purification, and cryopreservation Basic Protocol 3: Autologous hematopoietic stem cell transplantation Basic Protocol 4: Supportive care following recovery from aHSCT (Beyond 100 days) Basic Protocol 5: Ongoing evaluation of multiple sclerosis.

International audience; Background Palliative biliary drainage in patients with unresectable malignant biliary obstruction (MBO) frequently leads to biliary stent infection (BI), which could impact medical care. The aim of this study was to assess the risk factors for BI occurrence in patients after stenting procedure and the impact of BI on patient survival. Methods All consecutive patients hospitalized from 2014 to 2018 for MBO and biliary stenting were retrospectively included. Demographic, clinical, and microbiological characteristics of each BI episode during a 1-year follow-up were described. Documented BI was defined as the association of BI episode and confirmed blood stream infection (BSI). Univariate and multivariate analyses were performed to evaluate risk factors for the first BI occurrence. Results Among 180 patients, 56% were men (mean age of 69±12), and 54% have pancreatic cancer, 16% biliary cancer, 2% hepatic cancer, and 28% lymph node or metastatic compression; metallic stent was placed in 92%. A total of 113 BI episodes occurred in 74 patients, 55% of the first episodes occurring within 3 months after stenting. BI was documented in 56% of the episodes. Enterobacteriaceae were the most frequent pathogens found, while no yeasts were documented. Mortality rate in patients with BI was 64%. Multivariate analysis showed a significant difference in BI occurrence for two criteria: WHO score 3-4 (OR=8.79 [1.79-42.89]; p=0.007) and transpapillary stenting location (OR=3.72 [1.33-10.44]; p=0.013). Conclusion Since transpapillary stenting is a risk factor for BI, preserving the papilla as much as possible is a priority so as to avoid BI.

Immune checkpoint inhibitor (ICI)-related cytopenias have been poorly described. This study aimed to further characterize ICI-related cytopenias, using the French pharmacovigilance database. All grade ≥ 2 hematological adverse drug reactions involving at least one ICI coded as suspected or interacting drug according to the World Health Organization criteria and reported up to 31 March 2022, were extracted from the French pharmacovigilance database. Patients were included if they experienced ICI-related grade ≥ 2 cytopenia. We included 68 patients (75 ICI-related cytopenias). Sixty-three percent were male, and the median age was 63.0 years. Seven patients (10.3%) had a previous history of autoimmune disease. Immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) were the most frequently reported (50.7% and 25.3%, respectively). The median time to onset of ICI-related cytopenias was 2 months. Nearly half were grade ≥ 4, and three patients died from bleeding complications of refractory ITP and from thromboembolic disease with active AIHA. Out of 61 evaluable responses, complete or partial remission was observed after conventional treatment in 72.1% of ICI-related cytopenias. Among the 10 patients with ICI resumption after grade ≥ 2 ICI-related cytopenia, three relapsed. ICI-related cytopenias are rare but potentially life-threatening. Further studies are needed to identify risk factors of ICI-related cytopenias.

Two randomised trials (ASTIS, SCOT) of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) versus monthly Cyclophosphamide for severe Systemic Sclerosis (SSc) patients used similar inclusion criteria, but different primary endpoints: event-free-survival (EFS) at 24 months in ASTIS versus the global rank composite score (GRCS) at 54 months in SCOT. Here we analysed the French ASTIS cohort (n = 49) outcome using the same GRCS endpoint as reported in SCOT. All patients, randomised to AHSCT (n = 26) or Cyclophosphamide (n = 23), were evaluated for the non-parametric GRCS endpoint based on: death, EFS, forced vital capacity (FVC), Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 60 months. Secondary endpoints were: EFS, overall survival (OS), HAQ DI and organ status. In intention-to-treat analysis, the GRCS demonstrated superiority for AHSCT (median: 9 versus -19, p = 0.018), mRSS (Δ mRSS: -16 versus -9, p = 0.02), and HAQ-DI (ΔHAQ-DI: -0.89 versus -0.2, p = 0.05) with no significant difference in OS, EFS, lung, heart and kidney function between the groups. In conclusion, this study demonstrates long term benefits of non-myeloablative AHSCT when assessed by the five longitudinal measures within GRCS affording direct primary endpoint comparison between ASTIS and SCOT.

PURPOSE: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP. PATIENTS AND METHODS: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP. CONCLUSION: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.

BackgroundSafety of rechallenge of immune checkpoint inhibitor (ICI) after grade ≥2 immune-related adverse events (irAEs) leading to ICI discontinuation remains unclear.MethodsAll adverse drug reactions involving at least one ICI reported up to December 31, 2019 were extracted from the French pharmacovigilance database. Patients were included if they experienced at least one grade ≥2 irAE resulting in ICI discontinuation, with subsequent ICI rechallenge. The primary outcome was the recurrence of at least one grade ≥2 irAE in these patients after ICI rechallenge.ResultsWe included 180 patients: 61.1% were men (median age of 66 years), 43.9% had melanoma and 78.9% were receiving anti-programmed cell death 1. First ICI discontinuation was related to 191 irAEs. After ICI rechallenge, 38.9% of the patients experienced at least one grade ≥2 irAE. Among them, 70.0% experienced the same irAE, 25.7% a distinct irAE, and 4.3% both the same and a distinct irAE. Lower recurrence rates of irAEs were associated with rechallenge with the same ICI treatment (p=0.02) or first endocrine irAEs (p=0.003). Gastrointestinal irAEs were more likely to recur (p=0.007). The median duration from ICI discontinuation to rechallenge and the severity of the initial irAE did not predict recurrent irAEs after ICI rechallenge (p=0.53 and p=0.40, respectively).ConclusionsIn this study, 61.1% of the patients who discontinued ICI treatment for grade ≥2 irAEs experienced no recurrent grade ≥2 irAEs after ICI rechallenge. Although ICI rechallenge appears to be safe under close monitoring, it should always be discussed balancing usefulness of rechallenge, patient comorbidities and risk of recurrence of first irAE(s). Due to inherent bias associated with pharmacovigilance studies, further prospective studies are needed to assess risk factors that may influence patient outcomes after ICI rechallenge.

Immune checkpoint inhibitors (ICIs) have become the standard of care for several types of cancer due to their superiority in terms of survival benefits in first- and second-line treatments compared to conventional therapies, and they present a better safety profile (lower absolute number of grade 1–5 adverse events), especially if used in monotherapy. However, the pattern of ICI-related adverse events is totally different, as they are characterized by the development of specific immune-related adverse events (irAEs) that are unique in terms of the organs involved, onset patterns, and severity. The decision to resume ICI treatment after its interruption due to irAEs is challenged by the need for tumor control versus the risk of occurrence of the same or different irAEs. Studies that specifically assess this point remain scarce, heterogenous and mostly based on small samples of patients or focused only on the recurrence rate of the same irAE after ICI resumption. Moreover, patients with grade ≥3 irAEs were excluded from many of these studies. Herein, we provide a narrative review on the field of safety of ICI resumption after interruption due to irAE(s).

Background The most frequent myeloproliferative neoplasms are essential thrombocythemia and chronic myelogenous leukemia, which usually manifests with thrombocytosis. Only essential thrombocythemia is associated with morbidity during pregnancy (recurrent miscarriages, intrauterine fetal death, small for gestational age and preeclampsia). The aim of this paper is to describe outcomes of pregnancy in women with myeloproliferative neoplasms seen at a single academic institution. Methods Data were collected retrospectively from 2002 to 2015. Descriptive analyses were performed. Results Eighteen pregnancies in 13 patients and 17 births were identified. One patient had recurrent miscarriages. There were two intrauterine fetal deaths, three small for gestational age linked to vascular placenta pathology and one preeclampsia. All of these mothers harbored JAK2V617F mutation. Two out of three patients with small for gestational age developed a venous thrombosis in the two years following delivery. Conclusion Thrombocytosis associated with myeloproliferative neoplasms should be considered as a risk factor for maternal and fetal complications.

INTRODUCTION Although most infections occur within the first 2 years after splenectomy, the relatively short follow-up reported in many studies may underestimate the frequency of infections. The objective of the study was to determine the incidence of infective outcomes and factors associated with infection after splenectomy by studying a group of patients who underwent splenectomy over a 10-year period. METHODS A retrospective and monocentric study of patients who underwent splenectomy between January 1st, 1997 and December 31st, 2004 in a French university hospital. Age, sex, indication for splenectomy, infectious events, death, vaccination and antibiotic prophylaxis were collected in January 2015. RESULTS One hundred and sixty-five patients were included. The most common reasons for splenectomy were therapeutic hematological indications (37.5%). Ninety-seven per cent received pneumococcal vaccine. Prophylactic antibiotics were prescribed in 78% of patients. Thirty-seven patients had 42 severe infections with a median incidence rate of 4 years after splenectomy (2 days-12 years). The rate of infection after splenectomy declined over time but 57% occurred after 2 years and 14.3% after 10 years. Respiratory infections were the most common sites of infections. The incidence of infection differed according to age was highest among the elderly (HR=6.2; 95%CI: 1.4-27.1; after 65 years old) and underlying reason for splenectomy (P=0.02). There is no difference with or without prophylactic antibiotics. CONCLUSION After splenectomy, the incidence of severe infection declined over time but can occur after 10 years. The onset of infection is linked to age and reason for splenectomy.

Age is a well-known factor in solid tumours linked to lower adherence to guidelines. Scarce data exist for haematologic malignancies such as multiple myeloma (MM). The aim of the study was to investigate the relationships among age, adherence to guidelines in MM, and overall survival (OS).The Poitou-Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. Diagnosis, staging, prognosis, and first-line treatment were compared to the international guidelines. Three hundred and sixty-seven patients aged 36 to 93 years were included. Compliance to diagnostic procedure was 98%, staging 62%, prognosis 30%, and first-line treatment 89%. Cytogenetic analysis was compliant in 37%. Younger age was the strongest factor associated with compliant provision of care (odds ratio 14.4 [6.1-33.8] for

BACKGROUND Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients. METHODS We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017. RESULTS A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years. CONCLUSIONS This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure.

La sarcoidose est une maladie systemique auto-inflammatoire de type granulomatose. Son etiologie reste encore aujourd’hui mysterieuse. Elle atteint generalement les adultes jeunes dans toutes les ethnies. Elle est neanmoins plus frequente chez les patients d’origine africaine. Il existe une composante genetique en rapport avec le HLA de classe II, au niveau des alleles DR. C’est une maladie de la voie Th1 avec hyperproduction d’IL (Interleukine) 2,6,8,12,18,27, d’interferon gamma et de TNF (Tumor Necrosis Factor) alpha. Cet environnement cytokinique favorise la proliferation des lymphocytes T CD4+, mais aussi l’activation des lymphocytes B ainsi que celle de l’immunite innee. La lesion anatomopathologique caracteristique : le granulome epitheloide gigantocellulaire SANS necrose caseeuse n’est pas pathognomonique. Un bilan complet de granulomatose est necessaire avant de conclure, par defaut, a une sarcoidose. La presentation clinique typique (hors des services de neurologie) est avant tout ganglionnaire. Les adenopathies sont generalement mediastino-hilaires, bilaterales et symetriques, et non compressives. Les diagnostics differentiels sont alors le lymphome, la tuberculose, la maladie des griffes du chat et le cancer pulmonaire. Neanmoins, la sarcoidose peut atteindre potentiellement tous les organes : peau, œil, articulations, rate, cœur, rein, et bien sur le systeme nerveux central ou peripherique. L’atteinte cardiaque est plus frequente chez les mâles caucasiens, alors que l’atteinte cutanee et oculaire est plus frequente chez les femmes. Le traitement n’est necessaire qu’en cas d’atteinte viscerale grave (pulmonaire, oculaire, cardiaque, neurologique, etc…). Le traitement repose sur les corticoides dont la duree varie selon la localisation. En cas d’echec, un traitement immunosuppresseur par methotrexate, azathioprine ou un traitement par biotherapie de type infliximab ou adalimumab est possible. Le pronostic de la maladie est lie a la presence d’atteintes viscerales ainsi qu’a leur gravite et a la reponse au traitement. Environ 20 % des patients vont presenter un handicap relie a la sarcoidose et 3 a 5 % des patients vont deceder de cette maladie.

Simple Summary The therapeutics of multiple myeloma (MM) have greatly evolved in recent years both in the first-line setting and at relapse, and for both young and older patients. While still being considered as uncurable, MM survival has significantly increased. The development of immunotherapy (naïve and modern) largely contributed to these progresses, providing new effective drug combinations with acceptable toxicity profiles. Interestingly, some traditional concepts remain up to date, such as high-dose melphalan followed by autologous transplant, which can allow treatment intensification for eligible patients. Yet, with innovative response assessment techniques, allowing new response objectives, and treatment associations enabling profound responses, this, too, might be questioned in the near future. As the MM landscape is continuously moving, we sought to provide a review on the recent advances in the field of treatments in 2020. Abstract The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well acknowledged to prolong survival. Lenalidomide monotherapy is the only drug approved in that setting, but many innovations are expected. Older patients, now logically named not transplant-eligible, also took advantage of these breakthrough innovations as most of the recent drugs have a more acceptable safety profile than previous cytotoxic agents. For this heterogenous subgroup, geriatric assessment has become an essential tool to identify frail patients and provide tailored strategies. At relapse, options are now numerous, especially for patients who were not treated with lenalidomide, or not refractory at least. Concerning lenalidomide refractory patients, approved combinations are lacking, but many trials are ongoing to fill that space. Moreover, innovative therapeutics are increasingly being developed with modern immunotherapy, such as chimeric antigen receptor T-cells (CAR-T cells), bispecific antibodies, or antibody–drug conjugates. For now, these treatments are usually reserved to heavily pre-treated patients with a poor outcome. MM drug classes have tremendously extended from historical alkylating agents to current dominant associations with proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38/anti SLAMF7 antibodies. Plus, in only a couple of years, several new classes will enter the MM armamentarium, such as cereblon E3 ligase modulators (CELMoDs), selective inhibitors of nuclear export, and peptide–drug conjugates. Among the questions that will need to be answered in the years to come is the position of these new treatments in the therapeutic strategy, as well as the role of minimal residual disease-driven strategies which will be a key issue to elucidate. Through this review, we chose to enumerate and comment on the most recent advances in MM therapeutics which have undergone major transformations over the past decade.

The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hemophilia may require switching of clotting factor concentrates due to a variety of factors, but there have been perceived risks associated with switching, such as inhibitor development or suboptimal protection due to inadequate dosing while titrating treatment. Studies that look at patients switching from one clotting factor concentrate to another are categorized in terms of their primary and/or secondary objectives, notably biosimilarity and comparative pharmacokinetic studies and inhibitor development studies. Research on how best to switch concentrates with respect to dosing regimen are lacking, and currently a trial-and-error approach is used for dosing the new factor concentrate. In the future, studies looking at the predictability of pharmacokinetics (PK) of a new factor concentrate based on individual PK knowledge of the original factor concentrate may offer clinical benefit by providing a safer switching approach and protocol.

Allogeneic hematopoietic stem cell transplantation is a curative treatment for many hematological diseases. However, this procedure causes the patient to be susceptible to infection. Prophylactic treatments are administered in clinical practice even thought the level of evidence of their effectiveness is not always high. In addition, changes in the transplantation procedures - use of reduced intensity conditioning, development of alternative graft sources - must lead to a rethinking of attitudes towards prophylaxis. Our working group based its recommendations on a review of referential articles and publications on the subject found in the literature. These recommendations concern the prophylaxis of infections caused by HSV1, HSV2, varicella zoster, and hepatitis B, as well as anti-bacterial and digestive decontamination prophylaxis, prevention of pneumocystis, toxoplasmosis, tuberculosis, as well as prophylaxis of fungal infections. Other infectious agents usually involved in infections post-allotransplant have been the subject of another set of recommendations from the French Society of Bone Marrow Transplantation and Cellular Therapy.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France and updated recommendations for indications and follow-up in autologous hematopoietic stem cell transplantation in autoimmune and autoinflammatory diseases, previously published under the auspices of SFGM-TC.

Resume Introduction Le purpura thrombotique thrombocytopenique (PTT), caracterise par un deficit en ADAMTS13 (metalloprotease du facteur Willebrand) se manifeste par une microangiopathie thrombotique dont l’une des manifestations peut etre cardiaque. Observation Nous rapportons le cas d’une femme de 29 ans atteinte d’un PTT, au dernier trimestre de grossesse, qui s’etait initialement manifeste par un syndrome HELLP. Apres la cesarienne, l’atteinte cardiaque s’etait traduite par des douleurs thoraciques, des modifications electriques a l’ECG, une hypokinesie anteroseptale et une augmentation de la troponine. L’IRM cardiaque ne retrouvait pas d’anomalie en rapport avec une cardiopathie ischemique des gros troncs et confirmait l’hypokinesie. Conclusion Devant tout PTT, une atteinte cardiaque doit etre recherchee systematiquement par la realisation d’un ECG et le dosage de la troponine du fait du risque d’arret cardiaque.

Background: The treatment revolution of multiple myeloma (MM) with the advent of novel therapies, proteasome inhibitors, immunomodulators and newer drugs lead to increased survival. Clinical characteristics at diagnosis of Long-term survivor (>5 years after the start of treatment) were described; however data regarding the profile of lines of treatment is very limited. The aim of this study was to describe the profiles of response of this population. Methods: The Poitou‐Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. The follow-up date was December 31st, 2018. Patients (pts) alive after 5 years from the start of first line treatment were considered long-term survivors and their data were collected from their medical files. Three pts profiles were studied, very long responder (VLR) treated with a single line; long responder (LR) treated with [2-3] lines; and advanced (AdMM) [4 lines +[. Smoldering Myeloma, AL amyloidosis, lost to follow-up pts were excluded from the analysis. Results: Among the 396 MM registered, 177 were alive after 5 years, and 158 were included in the study. The mean age was 62.3 +/-11, sex ratio 1.2, 51% IgG, 25% IgA and 20% Light Chain isotype. ISS1 was 42%, 34% ISS2 and 14% ISS3. The median follow-up after the 5-year landmark was 39.9 +/-13 months and 52% pts died during follow-up. Overall, the median number of lines was 2.9 +/-2, 44% had at least one ASCT, 83% received Bortezomib, 72% Lenalidomide, 48% Thalidomide, 22% Pomalidomide, 20% Daratumumab (usually 3 lines+). VLR represented 19%, 27% LR, and 54% AdMM. In VLR group, 43% received a Bortezomib-based regimen (2 or 3 drugs) followed by ASCT, 47% a Melphalan-based regimen plus Thalidomide (MPT) or Bortezomib (MPV). In LR group, first line comprised: 39% Bortezomib-based regimen and ASCT versus 24% MPT and 15% MPV. Second line for LR group: 75% had Lenalidomide single agent or combination, 22% had a Bortezomib-based regimen, 17% had an ASCT. In the LR group, 45% received a third line: 40% Lenalidomide, mostly single agent, 25% a Bortezomib-based regimen and 3% had an ASCT. The AdMM group had a mean of 5.9 +/-1.6 lines (range 4 -11) and 56% of RR patients had at least one ASCT. Conclusion: Approximately 40% of MM were long-term survivors at 5 years from start of therapy in 2010, mainly on the basis of proteasome inhibitors and immunomodulators-based regimens plus use of ASCT. The vast majority of pts reached the 5 years cut-off with [4;+[ lines, and very few pts were real long-term survivors with an early prolonged control of Myeloma. Future perspective will look into 10 years long-term survival, including novel drug developments with the advent of immunotherapy. Disclosures Sabirou: AbbVie: Research Funding. Leleu:Janssen: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Merck: Honoraria; BMS: Honoraria.

Introduction Prognosis of elderly patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) remains poor as compare to young patients. Co-morbidities and physiological organ function impairment often lead to non-manageable toxicities and limit optimal chemotherapy. A decreased dose of CHOP (doxorubicin 25mg/m2 on D1, cyclophosphamide 400mg/m2 on D1, vincristine 1 mg TD on D1, and prednisone 40mg/m2 D1 to D5) chemotherapy with a conventional dose of rituximab (R-miniCHOP) displays a good compromise between efficacy and safety in this population. Lenalidomide, an oral immunomodulatory drug, in combination with RCHOP (R2-CHOP) has an acceptable toxicity and a potential higher efficacy in the non-GCB subtype, more frequent in elderly patients. The SENIOR study evaluated the tolerance and efficacy of the R2-miniCHOP regimen in comparison to the standard R-miniCHOP in patients ≥80 years with newly diagnosed DLBCL. Methods SENIOR is a multicentric, phase III, open-label, randomized trial in patients aged of 80 years or more with non-previously treated CD20+ DLBCL, age-adjusted IPI= 0 to 3, and Ann Arbor stage II to IV. Eligible patients were randomized 1:1 to standard R-miniCHOP or R2-miniCHOP on a 21-days cycle for 6 cycles. Patients were stratified by CD10 expression and age (≤85 years old or > 85 years old). The first cycle of rituximab was delivered by IV at the dose of 375mg/m2 on D1, then subcutaneoulsy at the dose of 1400mg TD on D1 of cycles 2-6. In the R2-miniCHOP arm, lenalidomide was administered at a dose of 10 mg TD on D1 to D14 every 3 weeks. Patients in the experimental arm had to receive deep venous thrombosis prophylaxis. This trial included a pre-phase treatment of prednisone (60 mg/m2 per os, days -7 to -1) and vincristine (1 mg TD IV, at D -7)). The primary end point was overall survival (OS). The statistical plan was based on the hypothesis of an increase of 15% of the 2y-OS (59 %-> 74%) in favor of the experimental arm. Secondary endpoints were PFS (Progression-Free Survival), EFS (Event-Free Survival), duration of response, DFS (disease-free survival), response rate at the end of the treatment (registration number NCT02128061) Results From August 2014 to September 2017, 249 patients were randomized (127 in R-miniCHOP arm and 122 in R2-miniCHOP arm). Median age was 83y (range 80-96). Baseline characteristics were balanced between the two arms (Table 1). 48 (19%) patients discontinued treatment (27 in R-miniCHOP and 21 in R2-miniCHOP), 27% for concurrent illness and 25% for progressive disease. In the safety set population (n = 241), the 6 planned cycles were delivered in 80% and 86% of patients in both arms. The % of planned dose for each R-miniCHOP compound was similar in both arms. 75% of patients received ≥ 75% of the planned dose of lenalidomide. Twenty (17%) patients experienced a dose reduction, 17 (85%) due to adverse events (AE). After a median follow up of 25.1 months, in an intention to treat analysis , R2-miniCHOP did not improve OS (2y-OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, p=.98, Figure 1), and no significant difference was observed based on stratified analysis on age or CD10 expression status. There was no significant difference in PFS, EFS, and DFS. ORR was 73% in R-miniCHOP arm and 83% in R2-miniCHOP arm. Deaths occurred in 42 and 43 patients in R-miniCHOP and R2-miniCHOP arm respectively, mainly due to lymphoma (60%). Four deaths, 2 in each treatment arm, were related to treatment toxicity. Grade 3-4 AE occurred in 53% of cases in R-miniCHOP arm and in 81% in R2-miniCHOP arm, with neutropenia in 17.7% vs 32.5%, infections 8.1% vs 13.7%, and pulmonary embolism (n=1, 0.8% vs n=7, 6%). Second primary malignancies occurred in 8 patients in R-miniCHOP arm and in 11 patients in R2-minCHOP arm. Both MNA and IADL scales correlated significantly with OS and PFS. Conclusion SENIOR study is the first prospective phase III trial in ≥80 years old patients with newly diagnosed DLBCL. Addition of lenalidomide to R-miniCHOP does not significantly improve OS irrespective to CD10 status and results in more adverse events. Rituximab delivered subcutaneously was safe and well tolerated. The overall 2y-OS of 66% was similar or higher to those reported in previously published LYSA trials (2y-OS = 59%, Peyrade et al. Lancet Oncol 2011; 2y-OS = 64.7%, Lancet Hematol 2017). Tumour Molecular characterisation are currently ongoing to identify patients that could benefit of R2-miniCHOP. Table 1 Disclosures Oberic: Janssen: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Feugier:Roche,: Membership on an entity's Board of Directors or advisory committees, Other: Travel expense and grants; Gilead,: Membership on an entity's Board of Directors or advisory committees, Other: travel support and grants ; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel support and grants; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel support and grants; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, grants. Thieblemont:Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria. Salles:Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria. Tilly:roche: Membership on an entity's Board of Directors or advisory committees; servier: Honoraria; merck: Honoraria; Gilead: Honoraria; Janssen: Honoraria; BMS: Honoraria; Karyopharm: Consultancy; Astra-Zeneca: Consultancy; Roche: Consultancy; Celgene: Consultancy, Research Funding. Haioun:servier: Honoraria; amgen: Honoraria; janssen cilag: Consultancy; takeda: Consultancy; novartis: Honoraria; celgene: Honoraria; gilead: Consultancy; celgene: Consultancy; roche: Consultancy. Jardin:amgen: Honoraria; Servier: Honoraria; celgene: Honoraria; roche: Honoraria; janssen: Honoraria.

La Presse Medicale - In Press.Proof corrected by the author Available online since vendredi 19 decembre 2014

Background: The presence of Janus Kinase 2 (JAK2) V617F mutation represents a major diagnostic criterion for detecting myeloproliferative neoplasms (MPN) and even in the absence of overt MPN, JAK2 V617F mutation is associated with splanchnic vein thrombosis. However, the actual prevalence and diagnostic value of the JAK2 V617F mutation in patients with cerebral venous thrombosis (CVT) are not known. The aims of this study were to assess the prevalence of JAK2 V617F mutation in a large group of consecutive CVT patients, to detect clinical, biological, and radiological features associated with the mutation, and to determine the long-term venous thrombosis recurrence rate in CVT patients with JAK2 mutation but without overt MPN in order to recommend the best preventive treatment. Methods: This was a prospective study conducted on consecutive patients with a first-ever radiologically confirmed CVT. JAK2 V617F mutation analysis was assessed in all the study subjects. JAK2 V617F-positive patients were followed up to detect new venous thrombotic events. Results: Of the 125 included subjects, 7 were found to have JAK2 V617F mutation (5.6%; 95% CI 2.3-11.2). Older age (p = 0.039) and higher platelet count (p = 0.004) were independently associated with JAK2 V617F positivity in patients without overt MPN. During a mean follow-up period of 59 (SD 46) months, 2 JAK2 V617F-positive patients presented with 4 new venous thromboembolic events. Conclusions: Screening for the JAK2 V617F mutation in CVT patients seems to be useful even in the absence of overt MPN and/or in the presence of other risk factors for CVT because of its relatively high prevalence and the risk of thrombosis recurrence.

The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27.

No other clinical abnormality was noted, except for recent weight loss. His biological data were normal. A computed tomography (CT) scan detected lymphadenopathies (left supraclavicular, left axillary and mesenteric), splenomegaly with nodules and a left kidney tumor. The bone marrow biopsy was normal. The 18 FDG PET image and SUV are presented in figure 1 . Left axillary lymphadenectomy revealed an NLPHL. Because of weight loss and disease diffusion, a splenectomy was performed to test for high-grade lymphoma transformation. The macroscopic examination revealed a 16.5 ! 10.5 ! 6.5-cm splenomegaly with two nodules. The performed histological and immunophenotypical analyses confirmed the diagnosis of diffuse large B cell lymphoma (DLBCL). The patient was treated by eight RCHOP cycles. Complete remission was still observed 42 months later. Nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) has been clearly individualized from classic Hodgkin’s lymphoma [1] . In the absence of a bulky tumor, the outcome is favorable [2] . However, with a median follow-up time of 6.5 years, up to 14% of patients experience a high-grade non-Hodgkin’s lymphoma (NHL) transformation [3] . This event usually imposes a new biopsy that may be guided by 18 fluorodeoxyglucose positron emission tomography ( 18 FDG PET), which has been proposed to discriminate between lowgrade and high-grade NHL [4, 5] . Schoder et al. [4] showed that the standardized uptake value (SUV, fig. 1) was lower in indolent than in aggressive NHL: 7.0 8 3.1 and 19.6 8 9.3, respectively. The suggested cut-off value for the distinction between indolent and high-grade lymphoma, with 100% specificity, was 13, using a receiver operating characteristic (ROC) technique. In a large series of NLPHL, the median SUV was 6.1 (range, 1.2–20.1) [6] . No SUV data were available concerning an aggressive transformation. So we report, for the first time, two cases of NLPHL high-grade transformation with 18 FDG PET SUV data. First case: a 51-year-old man presented in April 2008 with a 10-year history of left axillary lymphadenopathy. Received: June 12, 2012 Accepted after revision: October 14, 2012 Published online: January 11, 2013

Diffuse large B-cell lymphoma (DLBCL) CD20 positive is the most common type of aggressive non-Hodgkin lymphoma. The first-line standard chemotherapy treatment option is rituximab combined with cycl...