| 1. |
- Dreyling, Martin, et al.
(author)
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Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE) : a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
- 2024
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In: The Lancet. - 0140-6736. ; 403:10441, s. 2293-2306
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Journal article (peer-reviewed)abstract
- Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Funding: Janssen and Leukemia & Lymphoma Society.
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| 2. |
- Hadzidimitriou, Anastasia, et al.
(author)
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Is there a role for antigen selection in mantle cell lymphoma? : Immunogenetic support from a series of 807 cases
- 2011
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:11, s. 3088-3095
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Journal article (peer-reviewed)abstract
- We examined 807 productive IGHV-IGHD-IGHJ gene rearrangements from mantle cell lymphoma (MCL) cases, by far the largest series to date. The IGHV gene repertoire was remarkably biased, with IGHV3-21, IGHV4-34, IGHV1-8, and IGHV3-23 accounting for 46.3% of the cohort. Eighty-four of 807 (10.4%) cases, mainly using the IGHV3-21 and IGHV4-34 genes, were found to bear stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences and were placed in 38 clusters. Notably, the MCL stereotypes were distinct from those reported for chronic lymphocytic leukemia. Based on somatic hypermutation (SHM) status, 238/807 sequences (29.5%) carried IGHV genes with 100% germ line identity; the remainder (569/807; 70.5%) exhibited different SHM impact, ranging from minimal (in most cases) to pronounced. Shared replacement mutations across the IGHV gene were identified for certain subgroups, especially those using IGHV3-21, IGHV1-8, and IGHV3-23. Comparison with other entities, in particular CLL, revealed that several of these mutations were "MCL-biased." In conclusion, MCL is characterized by a highly restricted immunoglobulin gene repertoire with stereotyped VH CDR3s and very precise SHM targeting, strongly implying a role for antigen-driven selection of the clonogenic progenitors. Hence, an antigen-driven origin of MCL could be envisaged, at least for subsets of cases.
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| 3. |
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| 4. |
- Kustatscher, Evelyn, et al.
(author)
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Flora of The Late Triassic
- 2017. - 1
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In: The Late Triassic World: Earth in a Time of Transition. - New York : Springer International Publishing. - 9783319680088 ; , s. 545-622
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Book chapter (peer-reviewed)abstract
- The Triassic was a crucial period of botanical evolutionary innovations and plant diversification. Key plant groups (Bennettitales, Czekanowskiales, Gnetales and several modern fern and conifer families) originated during this span of time, together with some taxa putatively related to angiosperms. The composition of the various plant assemblages shows a more homogeneous flora globally than during the Permian. Nonetheless two major floristic provinces are distinguishable during the Late Triassic (Gondwana and Laurussia) together with several subprovinces (two within Gondwana, nine within Laurussia), based on palyno- and macro-floras.The latter are differentiated by contrasting taxonomic composition and group abundances related to different climatic and regional environmental conditions. Many plant families and genera are widely distributed in the Late Triassic, at least in the respective hemispheres. Based on the array of preserved damage types on leaves and wood, insect faunas appear to have recovered from the end-Permian mass extinction by the Late Triassic, with a major expansion of herbivory in Gondwana. All modern functional feeding groups (FFG) were present by the Triassic, including external foliage feeding, piercing-and-sucking, galling, leaf mining and seed predation, with some evidence for the development of very specialized feeding traits and egg-laying strategies.
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| 5. |
- Launis, Ahti, et al.
(author)
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A glimpse into the Carnian: Late Triassic plant fossils from Hopen, Svalbard
- 2015
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In: Norwegian Petroleum Directorate Bulletin. - Stavanger. - 0808-1409. ; 11, s. 129-136
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Journal article (peer-reviewed)abstract
- A small number of well-preserved plant fossils have been collected during recent fieldwork on Hopen in the Svalbard archipelago. The assemblage shows a composition typical of Carnian floras from central Europe and complements a recent study of old collections of Upper Triassic plant fossils from Svalbard. The new findings include already described species and some possibly new for Svalbard. The plant fossils are from well-dated Carnian beds on Hopen and confirm the earlier assumed Carnian age for plants collected on Svalbard from Upper Triassic sediments. A remarkable feature of this flora is the high number of plants, which are also described from Carnian floras from Austria and Switzerland, but also recorded from Franz Josef Land and other Arctic areas. The stratigraphic value of this flora is discussed.
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| 6. |
- McLoughlin, Stephen, 1964-, et al.
(author)
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Plant mobility in the Mesozoic: Disseminule dispersal strategies of Chineseand Australian Middle Jurassic to Early Cretaceous plants
- 2019
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In: Palaeogeography, Palaeoclimatology, Palaeoecology. - Amsterdam : Elsevier. - 0031-0182 .- 1872-616X. ; 515, s. 47-69
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Journal article (peer-reviewed)abstract
- Four upper Middle Jurassic to Lower Cretaceous lacustrine Lagerstätten in China and Australia (the Daohugou, Talbragar, Jehol, and Koonwarra biotas) offer glimpses into the representation of plant disseminule strategies during that phase of Earth history in which flowering plants, birds, mammals, and modern insect faunas began to diversify. No seed or foliage species is shared between the Northern and Southern Hemisphere fossil sites and only a few species are shared between the Jurassic and Cretaceous assemblages in the respective regions. Freesporing plants, including a broad range of bryophytes, are major components of the studied assemblages and attest to similar moist growth habitats adjacent to all four preservational sites. Both simple unadorned seeds and winged seeds constitute significant proportions of the disseminule diversity in each assemblage. Anemochory, evidenced by the development of seed wings or a pappus, remained a key seed dispersal strategy through the studied interval. Despite the rise of feathered birds and fur-covered mammals, evidence for epizoochory is minimal in the studied assemblages. Those Early Cretaceous seeds or detached reproductive structures bearing spines were probably adapted for anchoring to aquatic debris or to soft lacustrine substrates. Several relatively featureless seeds in all assemblages were potentially adapted to barochory or to endozoochory—the latter evidenced especially by the presence of smooth seeds in vertebrate gut contents and regurgitant or coprolitic masses. Hydrochory is inferred for several aquatic plants that notably bear small featureless seeds, particularly aggregated into detachable pods.
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| 7. |
- McLoughlin, Stephen, 1964-, et al.
(author)
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The diversity of Australian Mesozoic bennettitopsid reproductive organs
- 2018
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In: Palaeobiodiversity and Palaeoenvironments. - Berlin : Springer Science and Business Media LLC. - 1867-1594 .- 1867-1608. ; 98, s. 71-95
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Journal article (peer-reviewed)abstract
- Several dispersed reproductive organs of bennettitopsid gymnosperms are described and illustrated from Triassic to Cretaceous strata of Australia: Williamsonia eskensis sp. nov. (Middle Triassic), Williamsonia ipsvicensis sp. nov. (Upper Triassic), Williamsonia durikaiensis sp. nov. (Lower Jurassic), Williamsonia sp. (Lower Jurassic), Williamsonia rugosa sp. nov. (Middle Jurassic), Williamsonia gracilis sp. nov. (Lower Cretaceous), Cycadolepis ferrugineus sp. nov. (Lower Jurassic), Cycadolepis sp. (Lower Cretaceous), and Fredlindia moretonensis Shirley 1898 comb. nov. (Upper Triassic). Among these, W. eskensis appears to represent the oldest bennettitalean reproductive structure yet identified. Although global floras expressed less provincialism during the Mesozoic and many genera are cosmopolitan, Australian bennettopsid species appear to have been endemic based on the morphological characters of the reproductive structures. Bennettopsids have a stratigraphic range of around 210 million years in Australia and are widely and abundantly represented by leaf fossils, but only around 20 specimens of reproductive structures, of which half are attributed to Fredlindia, have been recovered from that continent’s geological archive. The extremely low representation of reproductive organs vis-à-vis foliage is interpreted to reflect a combination of physical disintegration of the seed-bearing units while attached to the host axis and, potentially, extensive vegetative reproduction in bennettopsids growing at high southern latitudes during the Mesozoic.
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| 8. |
- Pott, Christian, et al.
(author)
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Bennettitales in the Rhaetian flora of Wüstenwelsberg, Bavaria, Germany
- 2016
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In: Review of Palaeobotany and Palynology. - Amsterdam : Elsevier. - 0034-6667 .- 1879-0615. ; 232, s. 98-118
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Journal article (peer-reviewed)abstract
- The diverse bennettitalean plant remains from the Rhaetian of Wüstenwelsberg, Franconia, southern Germany,are described by means of macromorphological and epidermal anatomy; the study is part of the ongoing examinationof this recently excavated and excellently preserved fossil flora. The taxa identified include four species ofPterophyllum, one species of Anomozamites, two species of Nilssoniopteris and one species of Wielandiella withsterile leaves, bracts and ovulate reproductive organs. In addition, an enigmatic type of bennettitalean microsporangiateorgan has been obtained, remains of which from the Rhaetian of Greenland had been assigned toBennettistemon. However, the material from Wüstenwelsberg is much more complete and is assigned to a newgenus, viz. Welsbergia gen. nov., with its type species Welsbergia bursigera (Harris) comb. nov., based on theorgan's unique architecture. The microsporangiate organs are always exclusively associated with the sterile foliagePterophyllum aequale. Comparison of the flora fromWüstenwelsbergwith adjacent Rhaetian floras revealeddistinct local differences in the bennettitalean constitution, which are discussed in the light of palaeogeographyand plant dispersal patterns.
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| 9. |
- Pott, Christian, et al.
(author)
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Divaricate growth habit in Williamsoniaceae (Bennettitales): Unravelling the ecology of a key Mesozoic plant group
- 2014
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In: Palaeobiodiversity and Palaeoenvironments. - : Springer. - 1867-1594 .- 1867-1608. ; 94:2, s. 307-325
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Journal article (peer-reviewed)abstract
- Representatives of Williamsoniacae (Bennettitales) are usually restored as small-leafed shrubs or low-growing trees with densely interlaced stems bifurcating or trifurcating at broad angles —a growth form referred to as divaricating. A divaricate plant architecture has evolved independently in at least 18 modern plant families, of which the majority occur in New Zealand, where they constitute more than 10 % of the flora. Botanists favour two or three hypotheses on the benefits of a divaricating habit for modern plants. One hypothesis favours the evolution of this habit to protect the foliage and reproductive structures from browsing by large mammals or large flightless birds, such as the recently extinct moa or other ratites. Another argues that this habit evolved in response to a dry, windy or frosty climate, whereas a third regards divarication as having evolved to optimise foliar light harvesting. Our evaluation of these hypotheses with respect to the ecological pressures known to have been experienced by Williamsoniaceae in the mid-Mesozoic reveals that although defence against browsing tetrapods cannot be excluded as a selective pressure that promoted divarication in Williamsoniaceae, many of the anatomical and morphological features of this family appear to represent responses to local environmental conditions. In this context, representatives of Williamsoniaceae have many characters that are convergent with members of Banksiinae (Proteaceae), suggesting adaptation to open vegetation communities on nutrient-deficient soils.
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| 10. |
- Pott, Christian, et al.
(author)
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Ferns and fern allies from the Carnian (Upper Triassic) of Lunz am See, Lower Austria: A melting pot of Mesozoic fern vegetation
- 2018
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In: Palaeontographica. Abteilung B, Palaophytologie. - Bonn : E. Schweizerbart'sche Verlagsbuchhandlung. - 0375-0299. ; 297:1–6, s. 1-101
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Journal article (peer-reviewed)abstract
- The floral assemblage from the Carnian (Upper Triassic) of Lunz-am-See in Austria contains a rich and diverse array of ferns and fern allies, most of which have been considered only marginally, some have been described but more than a century ago and the majority have never been illustrated. Therefore, we here provide a detailed analysis of these taxa accompanied by extensive descriptions, detailed illustrations and colour restorations of the plants. We identified 17 species of lycophytes, sphenophytes and pteridophytes assignable to 14 genera in seven families. One taxon could be identified to class level only. One new genus of dipteridacean ferns (viz. Digitopteris C.Pott et Bomfleur gen. nov.), so far monotypic, is here described from Lunz with its type species Digitopteris repanda C.Pott et Bomfleur sp. nov. The Lunz flora comprises an interesting mixture of eusporangiate Marattiales and leptosporangiate Osmundales, Gleicheniales and Schizaeales; the former representing a rather primitive group of ferns. The co-occurrence of eusporangiate and leptosporangiate ferns renders the Lunz flora important given the fact that eusporangiate ferns were predominating over more modern, leptosporangiate forms during the Paleozoic, whereas they typically constitute only subordinate components in fern vegetation since the mid-Mesozoic until today. Among the leptosporangiate forms, the species from Lunz represent, due to their Triassic age, more primitive forms, which probably were rather growth-restricted thriving as herbaceous understorey layer among the shade of the eusporangiate, tree-like marattialean ferns.
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