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Demonstration of I TET2 i and I DNMT3A i mutations in B cells, myeloid cells, or hematopoietic progenitor cells have suggested that TFHL can emerge from clonal hematopoiesis (CH) in a multi-step process. Follicular helper T-cell lymphoma (TFHL) results from the oncogenic transformation of a TFH cell, driven by mutations in genes involved in epigenetic regulation ( I TET2 i , I DNMT3A, IDH2 i ) and T-cell signaling ( I RHOA i ). Meanwhile, bulk BM cells from 29 patients were sequenced with the same NGS panel and then compared to the mutations found in cfDNA (31 patients) and tumor biopsies (28 patients). [Extracted from the article]

KILT: A RANDOMIZED NON-COMPARATIVE PHASE II LYSA STUDY OF LACUTAMAB WITH GEMOX VERSUS GEMOX IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA B Background: b Peripheral T-cell Lymphoma (PTCL) is a heterogeneous group of mature T-cell lymphomas (TCL) with adverse outcomes. KIR3DL2 is a killer immunoglobulin-like receptor that is expressed across different subtypes of TCL, including approximately 40% of PTCL. [Extracted from the article]

Only one patient had detectable I TET2 i , I DNMT3A i , I IDH2 i , and I RHOA i mutations in the cfDNA and not in the tumor biopsy, corresponding to a tumor with low neoplastic cell content. By contrast, 3 patients had I DNMT3A i mutations, not affecting the R882 residue, detected in the cfDNA but not in the tumor likely corresponding to clonal hematopoiesis not related to the TFHL. Common I TET2 i mutations were detected in the tumor of 36/43 (84%) and in cfDNA of 33/43 (77%) patients, with a median variant allele frequency (VAF) of 17.75% vs. 9.8% respectively. [Extracted from the article]

Résumé Introduction Le purpura thrombotique thrombocytopénique (PTT) est une forme de microangiopathie thrombotique caractérisée par l’association d’une anémie hémolytique mécanique, d’une thrombopénie périphérique et de défaillances d’organe de sévérité variable. Méthodes Afin d’étudier la prise en charge du PTT, les caractéristiques cliniques, biologiques et thérapeutiques de 27 patients consécutifs atteints de PTT ont été analysées rétrospectivement dans deux centres hospitaliers français (Annecy et Grenoble). Résultats Tous les patients avaient une anémie hémolytique mécanique associée à une thrombopénie. Huit patients présentaient une fièvre. Treize patients avaient une atteinte rénale, caractérisée par une protéinurie ou une altération de la fonction rénale, et 18 avaient des anomalies neurologiques. L’association de ces 5 signes cardinaux du PTT n’était que rarement présente (11 %) et ne doit pas retarder le diagnostic de cette pathologie. L’activité de la protéine de clivage du facteur de Willebrand (ADAMTS13) était inférieure à 10 % chez les 27 patients. Un anticorps anti-ADAMTS13 était détecté chez 20 des 27 patients. Après échanges plasmatiques, glucocorticoïdes, et rituximab en deuxième intention, le taux de survie était de 85 % (23 survivants sur 27). Quatre patients décédaient, dont 2 dans un contexte de diagnostic tardif. Conclusion Le PTT est une microangiopathie thrombotique avec atteinte viscérale systémique dont la mortalité est élevée. Les traitements de sauvetage, basés sur l’expérience de quelques études et discutés en concertation avec le Centre de référence, permettent d’obtenir des réponses dans les formes les plus graves dans une majorité des cas. La sensibilisation des praticiens à ce diagnostic représente une démarche importante permettant de limiter davantage tout retard dans la prise en charge, afin d’améliorer encore le pronostic de ces patients. Introduction Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems associated with multiple organ dysfunctions and often severe disease course. Methods In order to enhance the understanding of TTP, the clinical features, laboratory characteristics, treatment and outcome of 27 patients with TTP were retrospectively analyzed and investigated in two centres (Annecy and Grenoble). Results All the 27 patients presented with haemolytic anemia and decreased platelet counts. Eight patients had fever. Thirteen patients had kidney involvement including proteinuria and renal function abnormalities. Eighteen patients had neurological manifestations. Association of the 5 characteristic features of TTP was rarely found (11%) which could lead to diagnosis delay. The von Willebrand factor-cleaving protease (ADAMTS13) activity was less than 10% in all patients. At the same time, plasma ADAMTS13 inhibitors were detected in 20 patients out of the 27. After treatment with plasma exchange, glucocorticoid and rituximab, 23 patients (85%) achieved complete remission. Four patients died, in which two cases were secondary to late diagnosis. Conclusion TTP is a thrombotic microangiopathy often associated with multiple organ dysfunctions. Salvage therapy, based on some studies experiences and discussed with the Reference Center, could help getting answers in most severe cases. Awareness of physicians is an important step to further limit any delay in medical care, and to further improve the prognosis of patients with TTP. [ABSTRACT FROM AUTHOR]

Background: Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia., Methods: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization., Results: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation., Conclusion: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan., Trial Registration: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549)., Competing Interests: JP: reports consultancy and honoraria at Blueprint Medicines, Amgen, F Hoffmann-La Roche, MSD, Bristol Myers Squibb, Alexion Pharmaceuticals, Novartis, Pfizer, Gilead, Boehringer Ingelheim, Swedish Orphan Biovitrum, and Apellis Pharmaceuticals; and honoraria from Swiss Biopharma. ND: has nothing to disclose SO: has nothing to disclose RPdL: has nothing to disclose PS: reports membership on an entity’s Board of Directors or advisory committees with Blueprint Medicines and Swedish Orphan Biovitrum AB; Honoraria, Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau with Alexion and Bristol Myers Squibb; Honoraria and Membership on an entity’s Board of Directors or advisory committees with MSD and Novartis. NS: reports membership of advisory committee with Alexion. MA-A: was an employee at the time of this study and held stock options. EP: is an employee of Swedish Orphan Biovitrum AB. RSMW: has received consulting fees, honoraria, research funding, and speaker’s bureau fees from Alexion and F. Hoffmann-La Roche Ltd.; and research funding and speaker’s bureau fees from Apellis. These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Panse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb <3.6 g/dL versus Alb ≥3.6 g/dL. In terms of mOS, multivariate analysis identified three PF: TP53mt (HR: 5.9 [1.77-19.5, P=0.004]), Alb <3.6 g/dL (HR: 5.2 [1.46- 18.5, P=0.011]), and ECOG=2 (HR: 3.7 [1.31-10.6, P=0.014]). Finally, a score combining TP53 status and Alb distinguished three populations based on the presence of 0, 1, or 2 PF. For these populations, mPFS was 7.8 years, 28 months, and 2.5 months, respectively. Our prolonged follow-up confirmed the efficacy of the RiBVD regimen, comparing it favorably to other regimens. TP53mt and hypoalbuminemia emerge as strong PF that can be easily integrated into prognostic scores for older adult patients with MCL.

Background: Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL., Methods: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375)., Findings: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown)., Interpretation: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial., Funding: Bristol-Myers Squibb., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests EB reports receiving research funding from Amgen and Bristol-Myers Squibb (BMS); honoraria from Kite, Gilead, Novartis, Roche, Incyte, Miltenyi Biotech, Takeda, and Sanofi; and participation on an advisory committee for Roche, Gilead, ADC Therapeutics, Takeda, Novartis, and Incyte. FM reports receiving consultancy fees from Roche, Gilead, and AbbVie and participation on advisory committees for Roche, Gilead, Novartis, BMS, AbbVie, Genmab, Miltenyi, Allogene Therapeutics, AstraZeneca, and Janssen. GC reports receiving honoraria from Gilead, Novartis, Mylteni, Sanofi, AbbVie, Takeda, Roche, Janssen, Roche, Celgene, Novartis and participation on advisory committees for MabQi, Ownards Therapeutics, AbbVie, Roche, and BMS. NF reports receiving consultancy fees from AstraZeneca, AbbVie, Eli Lilly, HUYA, and Novartis; research funding from Bayer, BMS, Chugai Pharma, Celgene, Genmab, and Incyte; honoraria from AstraZeneca, BMS, Chugai Pharma, Dainippon Sumitomo, Eisai, Janssen, Kyowa Kirin, Nippon Shinyaku, Novartis, Ono, Sanofi, Symbio, Takeda, and Celgene. R-OC reports receiving honoraria from Roche, Takeda, Merck, BMS, Gilead and Kite, AbbVie, ADC Therapeutics, and Incyte; research funding from Takeda and Gilead and Kite; honoraria from Roche, Takeda, Merck, BMS, Gilead and Kite, AbbVie, ADC Therapeutics, Incyte and AstraZeneca; and participation on advisory committees for Roche, Takeda, Merck, BMS, Gilead and Kite, ADC Therapeutics, Janssen, and Incyte. CPF reports receiving consultancy fees from AbbVie, AstraZeneca, Atarabio, Celgene and BMS, GenMab, Gilead and Kite, Incyte, Janssen, Morphosys, Ono Pharmaceutical, Roche, and Takeda; research funding from BeiGene; and speaker bureau fees from Celgene and BMS, Gilead and Kite, Incyte, Janssen, Roche, and Takeda; and travel support from Roche. FAd’A reports receiving research funding from Servier and Nordic Nanovector. PBS reports receiving consultancy fees from Amgen, Roche, Janssen, Gilead, Incyte, Morphosys, CTI Biopharma, BMS, Celegene, AbbVie, Takeda, BMS, Beigene, and Lilly; research funding from Roche; and honoraria from Amgen, Roche, Janssen, Gilead, Incyte, Morphosys, CTI Biopharma, BMS, Celegene, AbbVie, Takeda, BMS, Beigene, and Lilly. AG and MN are current employees and stock option holders at BMS. L-MF reports receiving honoraria from Roche, AbbVie, Janssen, and AstraZeneca. M-HD-L reports receiving research funding from Roche and Celgene; honoraria from Gilead and Amgen and travel support from Mundipharma. LdL reports receiving consultancy fees from Lunaphore Technologies and Bayer and honoraria from Novartis. PG reports receiving consultancy fees from Takeda; research funding from Takeda, Innate Pharma, Alderan, and Sanofi; and honoraria from Takeda Gilead. KT reports receiving consultancy fees from Ono Pharma, Meiji Seika Pharma, Yakuruto, Solasia Pharma, Meiji Seika Pharma, and HUYABIO; research funding from Kyowa-hakko and Kirin, Meiji Seika Pharma, BMS, Byer, Daiich-Sankyo, HUYABIO, and Regeneron Pharmaceuticals; and honoraria from Chugai Pharma, Eizai, and Meiji Seika Pharma. FL reports receiving honoraria from Kiowa, Miltenyi, and BMS; research funding from Roche and BMS; and travel support from Roche and Gilead. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and brentuximab-vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with noncutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. A total of 82 patients with R/R PTCL were included. The best overall response rate (ORR) was 68%, with 49% of patients in complete response (CR). In multivariable analysis, only the disease status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57%. Median duration of response was 15.4 months for patients in CR. With a median follow-up of 22 months, the median progression free survival (PFS) and overall survival (OS) were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 vs 4.8 months and not reached vs 12.4 months, respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events that were mainly hematologic. BBv is highly active in patients with R/R PTCL and should be considered as a one of the best options of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL., Methods: Patients with histologically confirmed CD20 + low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m 2 once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m 2 , on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS)., Results: Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; P = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm ( P = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT., Conclusion: SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The RELEVANCE trial (ClinicalTrials.gov identifier: NCT01650701) showed that lenalidomide plus rituximab (R 2 ) provided similar efficacy to rituximab plus chemotherapy (R-chemo) in patients with advanced-stage, previously untreated follicular lymphoma (FL). We report the second interim analysis of the RELEVANCE trial after 6 years of follow-up. Patients with previously untreated grade 1-3a FL were assigned 1:1 to R 2 or R-chemo, followed by rituximab maintenance. Coprimary end points were complete response (confirmed/unconfirmed) at week 120 and progression-free survival (PFS). At median follow-up of 72 months, 6-year PFS was 60% and 59% for R 2 and R-chemo, respectively (hazard ratio = 1.03 [95% CI, 0.84 to 1.27]). Six-year overall survival was estimated to be 89% in both groups. Median PFS and overall survival were not reached in either group. Overall response after progression was 61% and 59%, and 5-year estimated survival rate after progression was 69% and 74% in the R 2 and R-chemo groups, respectively. The transformation rate per year in the R 2 and R-chemo groups was 0.68% and 0.45%, and secondary primary malignancies occurred in 11% and 13% ( P = .34), respectively. No new safety signals were observed. R 2 continues to demonstrate comparable, durable efficacy and safety versus R-chemo in previously untreated patients with FL and provides an acceptable chemo-free alternative.

Background: Obinutuzumab monotherapy has shown promising efficacy in mantle cell lymphoma. We aimed to investigate the activity of obinutuzumab plus DHAP (dexamethasone, high-dose cytarabine, and cisplatin), measured by minimal residual disease quantitative (q)PCR status in the bone marrow after four cycles., Methods: LyMa-101 was a prospective, open-label, single-arm, phase 2 trial. Participants were enrolled from 28 hospitals in France. Newly diagnosed patients with mantle cell lymphoma (aged 18 to <66 years) who were eligible for autologous stem-cell transplantation received four cycles of obinutuzumab plus DHAP (obinutuzumab 1000 mg/m 2 intravenously on days 1, 8, and 15 at cycle 1 and day 1 at cycles 2, 3, and 4; dexamethasone 40 mg intravenously on days 1-4, cytarabine 2 g/m 2 intravenously every 12 h on day 1, and according to local investigator, cisplatin 100 mg/m 2 by continuous infusion over 24 h on day 1 or carboplatin area under the curve 5 or oxaliplatin 130 mg/m 2 ) every 21 days before transplantation, and 3 years of obinutuzumab (1000 mg/m 2 every 2 months) maintenance followed by minimal residual disease-based obinutuzumab on-demand maintenance. The primary outcome was minimal residual disease negativity in the bone marrow after four cycles of obinutuzumab plus DHAP at the end of induction, measured in the efficacy set (all minimal residual disease-informative [bone marrow or peripheral blood] patients who received at least one dose of obinutuzumab). Obinutuzumab plus DHAP was considered effective if bone marrow minimal residual disease negativity was 70% or more by intention to treat. The trial is closed to recruitment and registered with ClinicalTrials.gov, NCT02896582., Findings: 86 patients were enrolled between Nov 29, 2016, and May 2, 2018. 81 patients completed induction, 73 underwent autologous stem-cell transplantation, and 69 started maintenance therapy. 55 (75%) of 73 patients in the efficacy set reached minimal residual disease negativity in bone marrow at end of induction. According to the protocol definition, 18 (25%) of 73 patients in the efficacy set were minimal residual disease-positive: 12 patients who were minimal residual disease-positive in the bone marrow, plus two patients who progressed during induction, and four patients who did not have minimal residual disease assessment. The most common grade 3-4 treatment-emergent adverse events were anaemia (grade 3, 26 [31%] of 85 patients; grade 4, three [4%] of 85 patients) and neutropenia (grade 3, 13 [15%] of 85 patients; grade 4, 32 [38%] of 85 patients). 58 serious adverse events occurred during the induction phase. There were no treatment-related deaths., Interpretation: Obinutuzumab plus DHAP is a well tolerated regimen and has good activity for inducing minimal residual disease negativity in the bone marrow of transplant-eligible patients with mantle cell lymphoma. Obinutuzumab plus DHAP has potential activity as induction chemotherapy, with bone marrow minimal residual disease negativity potentially predicting long-term disease control., Funding: Roche SAS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Following an acute thrombotic thrombocytopenic purpura (TTP) episode, patients are at risk for relapse, and a careful long-term follow-up is needed. Adherence to the follow-up by patients implies a good understanding of the disease. However, TTP literacy in patients is currently unknown. To explore the TTP literacy in patients and identify factors associated with poor disease understanding, a questionnaire was developed focusing on patient's characteristics, knowledge about TTP and patients' actions in an emergency. The questionnaire was presented to 120 TTP patients in remission from the French National Registry for Thrombotic Microangiopathies. TTP literacy was low in 24%, intermediate in 43% and high in 33% of the patients. Low TTP literacy was associated with older age and low education level. Among the knowledge gaps identified, few patients knew that plasma exchange in acute phase is mandatory and has to be done daily (39%), 47% of participants did not consider themselves at risk for relapse, and 30% of women did not know that pregnancy exposes them to a greater risk of relapse. Importantly, few patients responded about life-saving actions in an emergency. Hence, the design of educational material should pay special attention to the age and education level of the target population focusing on the events leading to TTP, the importance of the emergency treatment, controllable predisposing factors for TTP development and patient attitude in an emergency., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68·2 (20·7) Versus 72·0 (17·8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81·1% Versus 66·3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo., (© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [ 18 F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively ( P <0.0001). Neither the mantle cell lymphoma index, nor fluorodeoxyglucose-positron emission tomography nor Ki67 positivity (cut off of ≥30%) showed a prognostic impact for survival. Hematologic grade 3-4 toxicities were mainly neutropenia (51%), thrombocytopenia (35%) and lymphopenia (65%). Grade 3-4 non-hematologic toxicities were mainly fatigue (18.5%), neuropathy (15%) and infections. In conclusion, the tested treatment regimen is active as frontline therapy in older patients with mantle cell lymphoma, with manageable toxicity. Minimal residual disease status after induction could serve as an early predictor of survival in mantle cell lymphoma. ClinicalTrials.gov: NCT 01457144 ., (Copyright© 2019 Ferrata Storti Foundation.)

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems associated with multiple organ dysfunctions and often severe disease course., Methods: In order to enhance the understanding of TTP, the clinical features, laboratory characteristics, treatment and outcome of 27 patients with TTP were retrospectively analyzed and investigated in two centres (Annecy and Grenoble)., Results: All the 27 patients presented with haemolytic anemia and decreased platelet counts. Eight patients had fever. Thirteen patients had kidney involvement including proteinuria and renal function abnormalities. Eighteen patients had neurological manifestations. Association of the 5 characteristic features of TTP was rarely found (11%) which could lead to diagnosis delay. The von Willebrand factor-cleaving protease (ADAMTS13) activity was less than 10% in all patients. At the same time, plasma ADAMTS13 inhibitors were detected in 20 patients out of the 27. After treatment with plasma exchange, glucocorticoid and rituximab, 23 patients (85%) achieved complete remission. Four patients died, in which two cases were secondary to late diagnosis., Conclusion: TTP is a thrombotic microangiopathy often associated with multiple organ dysfunctions. Salvage therapy, based on some studies experiences and discussed with the Reference Center, could help getting answers in most severe cases. Awareness of physicians is an important step to further limit any delay in medical care, and to further improve the prognosis of patients with TTP., (Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose: Although the translocation t(4;14) is supposed to be a primary event in multiple myeloma, we have been surprised to observe that in large relapse series of patients, the t(4;14) can be observed only in subpopulations of plasma cells, in contrast to what is seen at diagnosis. This observation raised the question of possible subclones harboring the translocation that would be observable only at the time of relapse., Experimental Design: To address this issue, we analyzed by FISH a cohort of 306 patients for whom we had at least two samples obtained at different disease phases., Results: We observed a "gain" of the t(4;14) in 14 patients, and conversely, a "loss" of the translocation in 11 patients. Two hypotheses were raised: either an acquisition of the translocation during evolution or the existence of small t(4;14)-positive subclones at the time of diagnosis. To address this question, we had the opportunity to analyze two patients at the time of diagnosis by RT-PCR (reverse transcription-polymerase chain reaction) to look for the chimeric Eμ-MMSET transcript, and one patient positive at diagnosis, but negative at relapse. The samples were positive, supporting the second hypothesis. Furthermore, the IGH sequences of two patients who "lose" the t(4;14) were identical at diagnosis and relapse, confirming the existence of a common ancestral clone., Conclusion: Thus, the conclusion of this study is that the t(4;14) is not a primary event in multiple myeloma and that it can be present in silent subclones at diagnosis, but also at relapse., (©2013 AACR.)

A young boy with a confirmed complete DiGeorge Syndrome (cDGS) underwent a peripheral blood mononuclear cell transplantation (PBMCT) from his HLA-identical sister at 4.5 years of age, without a conditioning regimen. Eight years later, he is healthy with good immunological functions in the presence of a stable mixed T-cell chimerism. Absence of recent thymic emigrants is confirmed. We observe an inverted CD4+/CD8+ ratio, related to the CD8 subset expansion, a skewing of the TCR repertoire, especially on the CD8+ subset and a telomere loss on the CD8+ cells compared to the donor. However, these anomalies do not seem to have an impact on functional immunity. PBMCT in cDGS using an HLA-matched sibling donor provides good long-lasting immunity and is an easy alternative to bone marrow transplantation and to thymic transplantation.