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.
The treatment of older patients with newly diagnosed acute myeloid leukemia (AML) depends on their fitness. Fit patients receive an induction chemotherapy similar to that of younger patients to ...achieve complete remission (CR). In patients <60, post-remission treatment is based on repeated courses of intermediate-to high-dose cytarabine with or without allogeneic stem cell transplantation (SCT) according to relapse risk. For patients over 60, there is no consensus about such a strategy, and ELN recommendations suggest intermediate-dose cytarabine (IDAC) for 2–3 cycles in favorable-risk genetics, i.e., 20% of patients. For the remaining 80%, the value of intermediate dose compared to lower-dose cytarabine has not been demonstrated to date, so there is no recommendation in this setting. Nevertheless, IDAC is routinely used, especially in patients selected for allogeneic SCT or as a standard comparator in clinical trials. The IDAC regimen has been adapted to find a compromise between efficacy and toxicity from the results of the Cancer and Leukemia Group B (CALGB) phase 3 trial.
Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare clonal autoimmune disease manifesting with hemolysis, thrombosis, or bone marrow failure. We present an atypical association of myasthenia ...gravis, aplastic anemia, and PNH occurring years after thymectomy. While this association might be extremely rare, it may not be coincidental as there is a common pathophysiology between PNH and aplastic anemia, with the latter reported in several thymoma/thymectomy cases. Eculizumab was introduced with good efficacy and without safety concern in our patient, leading to long‐term control of PNH without worsening of myasthenia gravis.
Paleobotanical data, with emphasis on anatomical characters in ferns and seed plants, confirm that the megaphyllous leaf evolved independently several times from the Middle Devonian to the Early ...Carboniferous. Fernlike cladoxylaleans and aneurophytalean progymnosperms possessed only megaphyll precursors homologous with the small megaphylls of archaeopteridalean progymnosperms. Different trends toward developing a large megaphyll, from the modification of lateral branch systems of some basal euphyllophytes, are shown by the fernlike rhacophytaleans and by the zygopterid and tedelean ferns. Zygopterids, with their tridimensional frond, petiole of the phyllophore type, and annulate sporangia, must be considered as the earliest undisputable ferns while the probably derived tedeleans have evolved toward a convergent filicalean‐type of frond. The leaf of other early ferns certainly derived through a minimal change in anatomy from other Devonian euphyllophytes. Early seed plant leaves probably evolved through the modification of an entire lateral branch system of aneurophytalean or stenokolean ancestors. In contrast to ferns, the seed plants early developed broad laminate pinnules with dichotomous nervation. The leaves of ferns and seed plants are not homologous, and fundamental differences in their petiole anatomy support the early divergence of the two groups.
Premise of research. Periderm is a protective secondary tissue that replaces the epidermis in stems and roots having secondary growth. The first periderm most commonly originates immediately below ...the epidermis, but in some species, it arises deeper in the stem, usually in the primary phloem. Periderm is a common feature of extant plants and has been reported in numerous fossil taxa. Here we investigate the presence of this tissue in a Carboniferous representative of the cladoxylopsids, an extinct group related to the ferns s.l.
Methodology. We describe anatomically preserved stems of Cladoxylon taeniatum with a well-preserved periderm from Tournaisian deposits in France and Germany. We also provide a short review of the current state of our knowledge on periderm production in Paleozoic plants, especially in relation to secondary vascular growth.
Pivotal results. The new specimens are 7–15 mm in diameter. They have a well-developed secondary xylem and a thin periderm that has a deep-seated origin in the innermost part of the cortex. This shows that Cladoxylon had the ability to accommodate secondary vascular growth with the production of a periderm that replaced the cortex and epidermis. Cladoxylon taeniatum is, to date, the only cladoxylopsid in which this feature is described, and it increases the diversity of anatomical strategies for secondary growth documented in the group. Changes in the nature and geometrical distribution of tissue between typical stems with a cortex and stems with a periderm suggest that C. taeniatum was non-self-supporting, a growth habit that also differs from that of most other older cladoxylopsids.
Conclusions. The new specimens increase the diversity of Paleozoic plants that produced both secondary vascular tissues and a periderm. Our review highlights the fact that anatomical homologies between the structures called “periderm” in these various taxa remain unclear; numerous questions about the origins of the periderm and the possible relation between secondary vascular growth and periderm production remain.
A survey of the anatomically preserved flora of the Grand-Croix cherts (Late Pennsylvanian, Saint-Etienne basin, France) is presented following a study of collections preserved in the Swedish Natural ...History Museum, Stockholm in complement to previous investigations on the original material kept in France. An exhaustive list of the flora is provided, confirming the particular importance of this permineralized plant assemblage that is one of the most diverse for the Late Pennsylvanian. The observed occurrence of taxa and organs confirms a previous quantitative study based on material in the French collections: cordaiteans are both the most common taxa and the most important contributors to peat volume, whilst leaves are the most common and abundant organs. However, the seed ferns are the most diverse group of plants before cordaiteans and ferns; the exceptional diversity of medullosan ovules is of particular interest. The Grand-Croix flora is compared with that of the nearby Early Permian basin of Autun. The two assemblages have 21 genera, but only 6 species, in common, and this may be explained by differences in age and taphonomy. The Grand-Croix flora is also similar to that of American coal balls of the same age and, despite taxonomic differences, it is significant that several species of ferns and seed ferns are common to the vegetation of the French limnic and American paralic basins.
The genus Gnetopsis was created for dispersed ovules preserved as compressions showing characteristic long apical expansions and for permineralized cupules (Gnetopsis elliptica) containing similar ...ovules, both from the late Pennsylvanian of central France. Subsequently, several species, on the basis of isolated ovules preserved as compressions of Mississippian to Pennsylvanian age, have been attributed to the same genus. Reexamination of Renault's original material of Gnetopsis shows that the permineralized ovules of G. elliptica have exceptionally well-preserved integument, nucellus, pollen chamber, and megagametophyte with archegonia. Similarity of the ovules of G. elliptica with those of Conostoma is confirmed, but apical expansions are not known in the last genus. Early Permian dispersed ovules, attributed to Gnetopsis (Gnetopsis augustodunensis), also have been reinvestigated; they are very similar to G. elliptica ovules but devoid of apical expansions and are here transferred to the genus Conostoma. Associated organs of stems assigned to the genus Heterangium are believed to have been produced by the same plant. New reconstructions of the ovule and cupule of G. elliptica are presented, along with an emended diagnosis of G. elliptica. The evolutionary significance of this multiovulate cupule is discussed, considering that G. elliptica is more similar in size and organization to some of the earliest (Devonian-Mississippian) cupules than to the contemporaneous Pennsylvanian uniovulate cupules.
The genusGnetopsiswas created for dispersed ovules preserved as compressions showing characteristic long apical expansions and for permineralized cupules (Gnetopsis elliptica) containing similar ...ovules, both from the late Pennsylvanian of central France. Subsequently, several species, on the basis of isolated ovules preserved as compressions of Mississippian to Pennsylvanian age, have been attributed to the same genus. Reexamination of Renault’s original material ofGnetopsisshows that the permineralized ovules ofG. ellipticahave exceptionally well-preserved integument, nucellus, pollen chamber, and megagametophyte with archegonia. Similarity of the ovules ofG. ellipticawith those ofConostomais confirmed, but apical expansions are not known in the last genus. Early Permian dispersed ovules, attributed toGnetopsis(Gnetopsis augustodunensis), also have been reinvestigated; they are very similar toG. ellipticaovules but devoid of apical expansions and are here transferred to the genusConostoma. Associated organs of stems assigned to the genusHeterangiumare believed to have been produced by the same plant. New reconstructions of the ovule and cupule ofG. ellipticaare presented, along with an emended diagnosis ofG. elliptica. The evolutionary significance of this multiovulate cupule is discussed, considering thatG. ellipticais more similar in size and organization to some of the earliest (Devonian-Mississippian) cupules than to the contemporaneous Pennsylvanian uniovulate cupules.
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