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Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management. In this article, we present a comprehensive set of recommendations for the management of HL, encompassing various aspects of diagnosis, risk stratification, evaluation, and treatment. These recommendations are based on the latest evidence-based guidelines, expert consensus opinions, and clinical trial data, aiming to provide clinicians with a practical framework for delivering optimal care to patients with HL., Competing Interests: Declaration of Competing Interest CR has received a research grant from Roche and personal fees and non-financial support from Janssen, Roche, Takeda, and Abbvie. ROC has received a research grant from Gilead and Takeda and personal fees and non-financial support from Janssen, Roche, Takeda, Merck/BMS, Abbvie, and Amgen. The other authors declare no competing interests. MA performed scientific and medical consul/ng for Novar/s, Janssen, Kite/Gilead and MSD and received research grants from Mnemo Therapeutics. R.D. reports honoraria from Novar/s and Takeda; and support for attending meetings and/or travel from Sanofi and Kite Pharma / Gilead. GM reports honoraria from Takeda, Bristol Myers Squibb, Gilead Kite, and Abbvie. All remaining authors have declared no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

According to current recommendations, older AML patients in first complete remission (CR) after induction chemotherapy should receive consolidation with intermediate-dose cytarabine (IDAC). However, no study has demonstrated the superiority of IDAC over other regimen. In this retrospective study, we compared the efficacy of mini-consolidations (idarubicin 8 mg/m 2 day 1, cytarabine 50 mg/m 2 /12 h, day 1-5) and IDAC. Inclusion criteria were newly diagnosed AML, age > 60 years, first CR after induction and at least 1 cycle of consolidation. Of the 796 included patients, 322 patients received mini-consolidations and 474 patients received IDAC. Mini-consolidation patients were older, and more often, they had de novo AML and unfavorable risk. The rate of allogeneic transplantation was higher in the IDAC group. The median number of cycles was higher in the mini-consolidation group (4 vs. 2; p < .0001). Median relapse-free survival was 18 months with mini-consolidations and 12 months with IDAC (p = .0064). In multivariate analysis, the risk of relapse or death was significantly higher in the IDAC group (p = .004). Median OS was 36 versus 31 months with mini-consolidations or IDAC, respectively (p = .46). In multivariate analysis, the consolidation regimen had no significant influence on OS (p = .43). In older AML patients, post-remission therapy with mini-consolidations represents an alternative to IDAC., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Late relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Metabolic programs contribute to hematopoietic stem and progenitor cell (HSPC) fate, but it is not known whether the metabolic regulation of protein synthesis controls HSPC differentiation. Here, we show that SLC7A1/cationic amino acid transporter 1-dependent arginine uptake and its catabolism to the polyamine spermidine control human erythroid specification of HSPCs via the activation of the eukaryotic translation initiation factor 5A (eIF5A). eIF5A activity is dependent on its hypusination, a posttranslational modification resulting from the conjugation of the aminobutyl moiety of spermidine to lysine. Notably, attenuation of hypusine synthesis in erythroid progenitors, by the inhibition of deoxyhypusine synthase, abrogates erythropoiesis but not myeloid cell differentiation. Proteomic profiling reveals mitochondrial translation to be a critical target of hypusinated eIF5A, and accordingly, progenitors with decreased hypusine activity exhibit diminished oxidative phosphorylation. This affected pathway is critical for eIF5A-regulated erythropoiesis, as interventions augmenting mitochondrial function partially rescue human erythropoiesis under conditions of attenuated hypusination. Levels of mitochondrial ribosomal proteins (RPs) were especially sensitive to the loss of hypusine, and we find that the ineffective erythropoiesis linked to haploinsufficiency of RPS14 in chromosome 5q deletions in myelodysplastic syndrome is associated with a diminished pool of hypusinated eIF5A. Moreover, patients with RPL11-haploinsufficient Diamond-Blackfan anemia as well as CD34+ progenitors with downregulated RPL11 exhibit a markedly decreased hypusination in erythroid progenitors, concomitant with a loss of mitochondrial metabolism. Thus, eIF5A-dependent protein synthesis regulates human erythropoiesis, and our data reveal a novel role for RPs in controlling eIF5A hypusination in HSPCs, synchronizing mitochondrial metabolism with erythroid differentiation.

Distinguishing between follicular lymphoma (FL) and nodal marginal zone lymphoma (NMZL) can be difficult when morphologic and phenotypic features are unusual and characteristic cytogenetic rearrangements are absent. We evaluated the diagnostic contribution of ancillary techniques-including fluorescence in situ hybridization (FISH)-detected 1p36 deletion; reverse-transcriptase, multiplex, ligation-dependent probe amplification (RT-MLPA); and next-generation sequencing (NGS)-for tumors that remain unclassified according to standard criteria. After review, 50 CD5-negative small B-cell lymphoid neoplasms without BCL2 and BCL6 FISH rearrangements were diagnosed as FLs (n = 27), NMZLs (n = 5), or unclassified (n = 18) based on the 2016 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. FISH helped identify the 1p36 deletion in 3 FLs and 1 unclassified tumor. Most classified FLs had an RT-MLPA germinal center B-cell (GCB) signature (93%) or were noncontributive (7%). Classified NMZLs had an RT-MLPA activated B-cell signature (20%), had an unassigned signature (40%), or were noncontributive (40%). Among unclassified tumors, the RT-MLPA GCB signature was associated with mutations most commonly found in FLs (CREBBP, EZH2, STAT6, and/or TNFRSF14) (90%). An RT-MLPA-detected GCB signature and/or NGS-detected gene mutations were considered as FL identifiers for 13 tumors. An activated B-cell signature or NOTCH2 mutation supported NMZL diagnosis in 3 tumors. Combining the RT-MLPA and NGS findings successfully discriminated 89% of unclassified tumors in favor of one or the other diagnosis. NGS-detected mutations may be of therapeutic interest. Herein, we detected 3 EZH2 and 8 CREBBP mutations that might be eligible for targeted therapies., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P<0.001) than patients with low TMTV. Multivariable analyses identified baseline elevated lactate dehydrogenase, DS-5, CAR T cells at M1 for PFS and baseline elevated lactate dehydrogenase, TMTV >80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia (R/R BCP-ALL) have very poor outcome. Blinatumomab as single agent has shown activity in R/R BCP-ALL. We aimed to assess the activity of blinatumomab in concomitant association with intensive chemotherapy. Seventeen patients with R/R BCP-ALL were treated with combination of blinatumomab and VANDA (etoposide, cytarabine, mitoxantrone, dexamethasone and asparaginase) regimen. Complete remission (CR) was achieved in 14/17 patient (82%) and 11/17 (65%) were transplanted. One-year leukaemia-free survival was 58.8% for the whole cohort and 90.9% for transplanted patients. These preliminary data suggest that the VANDA-blinatumomab salvage regimen leads to a very high rate of CR and HSCT in suitable patients., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

HHV-8 is an oncogenic Gammaherpesvirinae discovered in 1994 during the HIV pandemic. It is the causative agent of Kaposi's sarcoma, and is also associated with the occurrence of several aggressive B lymphoproliferative disorders. Most of them occur in an immunosuppression setting, usually due to HIV infection. Multicentric HHV8-associated Castleman's disease and KSHV Inflammatory Cytokine Syndrome (KICS) are primarily reactive entities with prominent systemic features. They illustrate the cytokinic storm induced by HHV-8 in its cell host. On the other hand, HHV-8 can drive proliferation and lymphomagenesis of its plasmablastic cell host, and is associated with a risk to develop aggressive lymphomas with plasmacytic differenciation. Primary effusion lymphoma usually localizes in body cavities and may affect other extra-nodal sites ; its prognostic is poor. Diffuse large B-cell lymphoma HHV-8, NOS affect more commonly nodes and blood and evolve from infected cell of HHV-8 associated Castleman disease. On the contrary, germinotropic lymphoproliferative disorders presents mainly as localized adenopathy with indolent course, and show polyclonality. Histology plays a key role in distinguishing these different entities and need expert reviewing, especially since they may be associated with each other. Besides lymphoproliferative disorders, HHV8 is associated with various hematological manifestations. The aim of this review is to provide an update on the presentation, diagnosis, and management of immunologic and hematologic complications associated with HHV-8., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Multiple myeloma (MM) is rare in young patients, especially before age 40 years at diagnosis, representing <2% of all patients with MM. Little is known about the disease characteristics and prognosis of these patients. In this study, we examined 214 patients diagnosed with MM at age ≤40 years over 15 years, in the era of modern treatments. Among them, 189 patients had symptomatic MM. Disease characteristics were similar to older patients: 35% had anemia, 17% had renal impairment, and 13% had hypercalcemia. The staging was ISS-1 in 52.4%, ISS-2 in 27.5%, and ISS-3 in 20.1%. Overall, 18% of patients had high-risk cytogenetics [del 17p and/or t(4;14)]. Ninety percent of patients received intensive chemotherapy followed by autologous stem cell transplant, and 25% of patients had allogeneic stem cell transplant predominantly at time of relapse. The median follow-up was 76 months, the estimated median overall survival was 14.5 years, and the median progression free-survival was 41 months. In multivariate analysis, bone lesions (hazard ratio [HR], 3.95; P = .01), high ISS score (HR, 2.14; P = .03), and high-risk cytogenetics (HR, 4.54; P < .0001) were significant risk factors for poor outcomes. Among predefined time-dependent covariables, onset of progression (HR, 13.2; P < .0001) significantly shortened overall survival. At 5 years, relative survival compared with same age- and sex-matched individuals was 83.5%, and estimated standardized mortality ratio was 69.9 (95% confidence interval, 52.7-91.1), confirming that MM dramatically shortens the survival of young patients despite an extended survival after diagnosis., (© 2021 by The American Society of Hematology.)

Peripheral T cell lymphomas are rare malignancies with aggressive course, with several different subtype described in the 2016 WHO classification. Their distribution across the world is heterogenous, with marked difference between Western and Asian country. Their clinical presentation often comprise extra-nodal involvement, B symptoms and immune system disorder which can lead to wrong diagnosis orientation. Make a right diagnosis need a experienced pathologist in close collaboration with clinical datas. Peripheral T cell lymphomas are in general associated with poor prognosis when treated with anthracyclines-based regimen, and several studies and trials focused on the use of intensified regimen or novel targeted agents, whose proper indication still remain to be clarified., (Copyright © 2020. Published by Elsevier Masson SAS.)

Postremission treatment is crucial to prevent relapse in acute myeloid leukemia (AML). High-dose cytarabine delivered every 12 hours on days 1, 3, and 5 (HDAC-135) is the standard of care for younger adult patients with AML. Although this standard has been unsuccessfully challenged by other treatment regimens, including multiagent chemotherapy, the timing of HDAC administration has attracted little attention. Here, we retrospectively compared the safety, efficacy, and health care resource consumption associated with HDAC-135 and another standard, condensed HDAC-123 regimen, as consolidation treatment in younger AML patients in first complete response. This study included 221 patients (median age, 46.6 years; range, 18-60 years). HDAC-123 and HDAC-135 were used in 92 and 129 patients, respectively. Both regimens were associated with similar rates of relapse-free survival, cumulative incidence of relapse, nonrelapse mortality, and overall survival, including in core binding factor AML subgroup in which levels of minimal residual disease reduction were similar in both schedules. Hematological recovery times regarding neutrophils and platelets were significantly shorter in patients receiving HDAC-123, with an average difference of 3 to 4 days for each consolidation cycle. The total duration of hospitalization for the whole postremission program was shorter with HDAC-123 (32 days; interquartile ratio [IQR], 22.0,36.5) compared with HDAC-135 (41 days; IQR, 30.5, 50.0) (P < .0001). In conclusion, the condensed HDAC-123 regimen induced faster hematological recovery and therefore significantly reduced the length of hospital stay without affecting treatment response or outcome in younger AML patients., (© 2020 by The American Society of Hematology.)

A new fossil peronosporomycete from the upper Visean (Mississippian) of France occurs as a globose oogonium at the tip of a thin-walled hypha. The oogonium surface is prominently ornamented by densely spaced, long and subtle, straight or once to several times furcated thread-like extensions; many possess an opaque, bulb-like swelling at base. Antheridia adpressed to the oogonium are clavate and paragynous. This fossil represents only the third record of an unequivocal peronosporomycete from the Carboniferous, and thus provides important details about the evolutionary history of this group of organisms., (Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Abundant charcoalified seed fern (pteridosperm) pollen organs and ovules have been recovered from Late Viséan (Mississippian 330 Ma) limestones from Kingswood, Fife, Scotland. To overcome limitations of data collection from these tiny, sometimes unique, fossils, we have combined low vacuum scanning electron microscopy on uncoated specimens with backscatter detector and synchrotron radiation X-ray tomographic microscopy utilizing the Materials Science and TOMCAT beamlines at the Swiss Light Source of the Paul Scherrer Institut. In combination these techniques improve upon traditional cellulose acetate peel sectioning because they enable study of external morphology and internal anatomy in multiple planes of section on a single specimen that is retained intact. The pollen organ Melissiotheca shows a basal parenchymatous cushion bearing more than 100 sporangia on the distal face. Digital sections show the occurrence of pollen in some sporangia. The described ovule is new and has eight integumentary lobes that are covered in spirally arranged glandular hairs. Virtual longitudinal sections reveal the lobes are free above the pollen chamber. Results are applied in taxonomy and will subsequently contribute to our understanding of the former diversity and evolution of ovules, seeds, and pollen organs in the seed ferns, the first seed-bearing plants to conquer the land.

Structurally preserved periderm of the lycophyte Lepidodendron rhodumnense from the Visean (Mississippian) of central France contains a peronosporomycete (Combresomyces cornifer gen. sp. nov.) that occurs in the form of pyriform to subglobose terminal oogonia. On the surface is a conspicuous ornamentation, which may have formed through condensation of a mucilaginous extra-oogonial wall secretion. Some oogonia contain thin-walled spherules, which may represent (walled) oospheres or spores of an endoparasitic fungus (?chytrid), whereas single, large spheres in the interior are interpreted as oospores. Antheridia adpressed to several of the specimens are clavate and paragynous. This discovery sheds light on the morphology and biology of peronosporomycetes in a terrestrial ecosystem some 330My ago. Although the organism occurs exclusively in the periderm of L. rhodumnense, it is not known whether it represents a symptomless endophyte, pathogen, or saprotroph.

Trunk woods of Early Carboniferous Protopitys buchiana show the earliest example of tylose formation and the first record for a progymnosperm. Protopitys tyloses are more densely located in inner trunk woods and near growth layer boundaries. We suggest, therefore, that an altered physiological state of living ray cells, during dormancy and/or following water stress, was necessary to make the woods vulnerable to tylose formation. Coupled with the distribution and proximity of abundant wood ray parenchyma to large xylem conducting cells, the positions of conduits filled with tyloses can be interpreted as ecophysiological responses of the plant to changes in local environment. In addition, some xylem conducting cells might have functioned as vessels. Fungal hyphae are present in some tracheary cells and in some areas with tyloses, but there is no evidence for wood trauma; we conclude, therefore, that these particular cases of tyloses are probably not induced by wound trauma. Protopitys buchiana wood thus shows structure/function similarities to modern woods with vessels, such as those of dicot angiosperms. This implies that ancient and modern plant ecophysiological responses correlate well with the physical parameters of their cellular construction.