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1.
J Colloid Interface Sci ; 672: 600-609, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38857568

RESUMEN

Solar-light driven oxidation of benzylic alcohols over photocatalysts endows significant prospects in value-added organics evolution owing to its facile, inexpensive and sustainable process. However, the unsatisfactory performance of actual photocatalysts due to the inefficient charge separation, low photoredox potential and sluggish surface reaction impedes the practical application of this process. Herein, we developed an innovative Z-Scheme Cs3BiBr9 nanoparticles@porous C3N4 tubes (CBB-NP@P-tube-CN) heterojunction photocatalyst for highly selective benzyl alcohol oxidation. Such composite combining increased photo-oxidation potential, Z-Scheme charge migration route as well as the structural advantages of porous tubular C3N4 ensures the accelerated mass and ions diffusion kinetics, the fast photoinduced carriers dissociation and sufficient photoredox potentials. The CBB-NP@P-tube-CN photocatalyst demonstrates an exceptional performance for selective photo-oxidation of benzylic alcohol into benzaldehyde with 19, 14 and 3 times higher benzylic alcohols conversion rate than those of C3N4 nanotubes, Cs3Bi2Br9 and Cs3Bi2Br9@bulk C3N4 photocatalysts, respectively. This work offers a sustainable photocatalytic system based on lead-free halide perovskite toward large scale solar-light driven value-added chemicals production.

2.
Adv Mater ; 36(26): e2314056, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38618981

RESUMEN

A thorough and quantitative understanding of the fate of excitons in covalent-organic frameworks (COFs) after photoexcitation is essential for their augmented optoelectronic and photocatalytic applications via precise structure tuning. The synthesis of a library of COFs having identical chemical backbone with impeded conjugation, but varied morphology and surface topography to study the effect of these physical properties on the photophysics of the materials is herein reported. The variation of crystallite size and surface topography substantified different aggregation pattern in the COFs, which leads to disparities in their photoexcitation and relaxation properties. Depending on aggregation, an inverse correlation between bulk luminescence decay time and exciton binding energy of the materials is perceived. Further transient absorption spectroscopic analysis confirms the presence of highly localized, immobile, Frenkel excitons (of diameter 0.3-0.5 nm) via an absence of annihilation at high density, most likely induced by structural torsion of the COF skeletons, which in turn preferentially relaxes via long-lived (nanosecond to microsecond) excimer formation (in femtosecond scale) over direct emission. These insights underpin the importance of structural and topological design of COFs for their targeted use in photocatalysis.

4.
Clin Transl Sci ; 17(3): e13742, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38494922

RESUMEN

Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ-67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first-in-human, open-label, phase I, dose-escalation/dose-expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ-67571244 was administered intravenously or subcutaneously using step-up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose-escalation cohorts (n = 68) and before starting dose-expansion. Overall, 11 (16.2%) patients experienced ≥1 dose-limiting toxicity; all experienced ≥1 treatment-emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ-67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion-related reactions, and elevated liver function tests. A prolonged step-up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T-cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ-67571244 efficacy was not achieved, thus MTD and RP2D were not determined.


Asunto(s)
Antineoplásicos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Antineoplásicos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunología
5.
Br J Haematol ; 204(3): 892-897, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38013238

RESUMEN

Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut-off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)-CMML. Five-year survival was longer for OM-CMML than for other patients (p < 0.001). Multivariate analysis identified OM-CMML as a favourable prognostic factor (HR 0.58; p = 0.002). The 5-year cumulative incidence of progression to classical CMML was 47%. Older age and transfusion dependence were adverse prognostic factors for OM-CMML. Our results support the inclusion of OM-CMML in the CMML category as a subtype with superior outcomes.


Asunto(s)
Leucemia Mielomonocítica Crónica , Humanos , Leucemia Mielomonocítica Crónica/diagnóstico , Leucocitosis , Pronóstico
6.
An. Fac. Cienc. Méd. (Asunción) ; 56(3): 118-120, 20231201.
Artículo en Español | LILACS | ID: biblio-1519423

RESUMEN

Actualmente existe una tendencia mundial de desplazamiento de la población rural hacia áreas cada vez más urbanizadas. Existe evidencia que informa que el desarrollo de las enfermedades mentales tiene relación importante con factores tanto internos (por ejemplo, genéticos) y externos (el ambiente, entre otros). Con respecto a esto último, la manera en la que el entorno afecta a la salud mental es un objeto de estudio de interés global y se ha reportado que las áreas urbanas presentan mayores tasas de trastornos mentales comunes en comparación con las rurales. En el caso de la psicosis, por más de que el factor genético sea el más demostrado (y estudiado en los últimos años), el factor ambiental representando por el ambiente urbano ya ha sido analizado por investigadores a inicios del siglo 20. Desde allí, a lo largo de los años se obtuvo evidencia repetida que lo respalda como un factor de riesgo. Se ha encontrado que, además, existe relación con el grado de exposición, lo que hace pensar que la causa no solamente se limita a la transición del área rural al área urbana, sino que están involucrados factores sociales, económicos y medioambientales más profundos como la disparidad social, inseguridad, contaminación, entre otros 1. Ya en las últimas décadas del siglo 20, investigadores informaron de un aumento de la incidencia de esquizofrenia de 1,65 en hombres que vivían ciudades sobre sus contrapartes de origen rural. Años después, otros estudios han reportado esta variación en la incidencia de primeros episodios psicóticos a través del gradiente social urbano-rural, así como una relación entre el aumento de hospitalización por esquizofrenia con el grado de urbanización.

8.
Int. j. morphol ; 41(5): 1480-1484, oct. 2023. ilus, tab
Artículo en Español | LILACS | ID: biblio-1521043

RESUMEN

Testut & Latarjet (1980), Bouchet & Cuilleret (1986), Latarjet & Liard (2005) y Rouvière & Delmas (2005) describen las relaciones intrínsecas del pedículo renal (PR) a partir de dos planos coronales, siendo la PER el elemento que limita entre ambos. Trivedi et al. (2011) demostró relaciones entre los elementos del PR que no coinciden con las descripciones aportadas por dichos autores.Conocer las posibles variantes en las relaciones intrínsecas del PR es de suma importancia en prácticas quirúrgicas como el trasplante renal (García de Jalón Martínez et al., 2003; Batista Hernández et al., 2010). Por lo tanto, el objetivo del presente trabajo fue analizar las variables relaciones entre los elementos que conforman el PR en la región yuxtahiliar del riñón. Se estudiaron 23 PR, formolizados al 10 % y provistos por el Equipo de Disección de la Segunda Cátedra de Anatomía de la Universidad de Buenos Aires. Se clasificaron los PR en dos grupos. En el Grupo I, las afluentes de origen de la vena renal (AOVR) se hallaban en el mismo plano coronal. En el grupo II, las AOVR se encontraban en diferentes planos coronales. Cada grupo fue subdividido en distintos patrones. Los patrones I y II, de mayor incidencia, fueron asociados al grupo I y los patrones III, IV y V al grupo II. En el patrón I, las AOVR eran anteriores a la pelvis renal (PER) y posteriores a la arteria prepiélica (APP). En el patrón II, las AOVR eran anteriores a la PER y a la APP. Los patrones I y II conforman el grupo I y presentaron mayor número de incidencia en nuestra investigación. Existen también variantes que inciden con menor frecuencia que dichos patrones, estas comprenden el grupo II de la clasificación planteada en el presente trabajo.


SUMMARY: Testut & Latarjet (1980), Bouchet & Cuilleret (1986), Latarjet & Liard (2005) y Rouvière & Delmas (2005) describe the intrinsic relationships of the renal pedicle (PR) from two coronal planes, the renal pelvis (PER) being the element that limits between both. Trivedi et al. (2011) showed relationships between the elements of the RP that do not coincide with the descriptions provided by these authors. Knowing the possible variants in the intrinsic relationships of the RP is of the utmost importance in surgical practices such as renal transplantation (García de Jalón Martínez et al., 2003). Therefore, the objective of this study is to analyze the variable relationships between the elements that make up the RP in the juxtahilar region of the kidney. 23 RP were studied, formalized at 10 % and provided by the Dissection Team of the Second Chair of Anatomy of the University of Buenos Aires. PRs were classified into two groups. In Group I, the tributaries of origin of the renal vein (RVOA) were in the same coronal plane. In group II, the AOVRs were in different coronal planes. Each group was subdivided into different patterns. Patterns I and II, with the highest incidence, were associated with group I and patterns III, IV and V with group II. In pattern I, the VROA were anterior to the renal pelvis (PER) and posterior to the prepelvic artery (PPA). In pattern II, AOVRs were prior to PER and APP. Patterns I and II make up group I and presented a higher number of incidence in our investigation. There are also variants that occur less frequently than these patterns, these comprise group II of the classification proposed in this work.


Asunto(s)
Humanos , Arteria Renal/anatomía & histología , Venas Renales/anatomía & histología , Pelvis Renal , Cadáver , Variación Anatómica , Riñón
9.
Chemphyschem ; 24(22): e202300437, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37669423

RESUMEN

The hydrolysis of the phosphonate ester linker during the synthesis of hybrid (organic-inorganic) TiO2 nanoparticles is important when forming porous hybrid organic-inorganic metal phosphonates. In the present work, a method was utilized to control the in-situ partial hydrolysis of diphosphonate ester in the presence of a titania precursor as a function of acid content, and its impact on the hybrid nanoparticles was assessed. Organodiphosphonate esters, and more specific, their hydrolysis degree during the formation of hybrid organic-inorganic metal oxide nanoparticles, are relatively under explored as linkers. Here, a detailed analysis on the hydrolysis of tetraethyl propylene diphosphonate ester (TEPD) as diphosphonate linker to produce hybrid TiO2 nanoparticles is discussed as a function of acid content. Quantitative solution NMR spectroscopy revealed that during the synthesis of TiO2 nanoparticles, an increase in acid concentration introduces a higher degree of partial hydrolysis of the TEPD linker into diverse acid/ester derivatives of TEPD. Increasing the HCl/Ti ratio from 1 to 3, resulted in an increase in degree of partial hydrolysis of the TEPD linker in solution from 4 % to 18.8 % under the applied conditions. As a result of the difference in partial hydrolysis, the linker-TiO2 bonding was altered. Upon subsequent drying of the colloidal TiO2 solution, different textures, at nanoscale and macroscopic scale, were obtained dependent on the HCl/Ti ratio and thus the degree of hydrolysis of TEPD. Understanding such linker-TiO2 nanoparticle surface dynamics is crucial for making hybrid organic-inorganic materials (i. e. (porous) metal phosphonates) employed in applications such as electronic/photonic devices, separation technology and heterogeneous catalysis.

12.
ACS Nano ; 17(17): 16943-16951, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37602824

RESUMEN

Rhodium-platinum core-shell nanoparticles on a carbon support (Rh@Pt/C NPs) are promising candidates as anode catalysts for polymer electrolyte membrane fuel cells. However, their electrochemical stability needs to be further explored for successful application in commercial fuel cells. Here we employ identical location scanning transmission electron microscopy to track the morphological and compositional changes of Rh@Pt/C NPs during potential cycling (10 000 cycles, 0.06-0.8 VRHE, 0.5 H2SO4) down to the atomic level, which are then used for understanding the current evolution occurring during the potential cycles. Our results reveal a high stability of the Rh@Pt/C system and point toward particle detachment from the carbon support as the main degradation mechanism.

13.
Heliyon ; 9(7): e17662, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37449178

RESUMEN

Biomethane is a renewable natural gas substitute produced from biogas. Storage of this sustainable energy vector in confined clathrate hydrates, encapsulated in the pores of a host material, is a highly promising avenue to improve storage capacity and energy efficiency. Herein, a new type of periodic mesoporous organosilica (PMO) nanotubes, referred to as hollow ring PMO (HR-PMO), capable of promoting methane clathrate hydrate formation under mild working conditions (273 K, 3.5 MPa) and at high water loading (5.1 g water/g HR-PMO) is reported. Gravimetric uptake measurements reveal a steep single-stepped isotherm and a noticeably high methane storage capacity (0.55 g methane/g HR-PMO; 0.11 g methane/g water at 3.5 MPa). The large working capacity throughout consecutive pressure-induced clathrate hydrate formation-dissociation cycles demonstrates the material's excellent recyclability (97% preservation of capacity). Supported by ex situ cryo-electron tomography and x-ray diffraction, HR-PMO nanotubes are hypothesized to promote clathrate hydrate nucleation and growth by distribution and confinement of water in the mesopores of their outer wall, along the central channels of the nanotubes and on the external nanotube surface. These findings showcase the potential for application of organosilica materials with hierarchical and interconnected pore systems for pressure-based storage of biomethane in confined clathrate hydrates.

14.
Blood Adv ; 7(19): 5799-5811, 2023 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-37450374

RESUMEN

Germ line predisposition in acute myeloid leukemia (AML) has gained attention in recent years because of a nonnegligible frequency and an impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigated the presence of germ line variants (GVs) in 288 genes related to cancer predisposition in 47 patients with available paired, tumor-normal material, namely bone marrow stroma cells (n = 29), postremission bone marrow (n = 17), and saliva (n = 1). These patients correspond to 2 broad AML categories with heterogeneous genetic background (AML myelodysplasia related and AML defined by differentiation) and none of them had phenotypic abnormalities, previous history of cytopenia, or strong cancer aggregation. We found 11 pathogenic or likely pathogenic variants, 6 affecting genes related to autosomal dominant cancer predisposition syndromes (ATM, DDX41, and CHEK2) and 5 related to autosomal recessive bone marrow failure syndromes (FANCA, FANCM, SBDS, DNAJC21, and CSF3R). We did not find differences in clinical characteristics nor outcome between carriers of GVs vs noncarriers. Further studies in unselected AML cohorts are needed to determine GV incidence and penetrance and, in particular, to clarify the role of ATM nonsense mutations in AML predisposition.


Asunto(s)
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/epidemiología , Síndromes Mielodisplásicos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/epidemiología , Mutación de Línea Germinal , Genotipo , ADN Helicasas/genética
15.
Chem Mater ; 35(7): 2988-2998, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37063593

RESUMEN

Colloidal 2D semiconductor nanocrystals, the analogue of solid-state quantum wells, have attracted strong interest in material science and physics. Molar quantities of suspended quantum objects with spectrally pure absorption and emission can be synthesized. For the visible region, CdSe nanoplatelets with atomically precise thickness and tailorable emission have been (almost) perfected. For the near-infrared region, PbS nanosheets (NSs) hold strong promise, but the photoluminescence quantum yield is low and many questions on the crystallinity, atomic structure, intriguing rectangular shape, and formation mechanism remain to be answered. Here, we report on a detailed investigation of the PbS NSs prepared with a lead thiocyanate single source precursor. Atomically resolved HAADF-STEM imaging reveals the presence of defects and small cubic domains in the deformed orthorhombic PbS crystal lattice. Moreover, variations in thickness are observed in the NSs, but only in steps of 2 PbS monolayers. To study the reaction mechanism, a synthesis at a lower temperature allowed for the study of reaction intermediates. Specifically, we studied the evolution of pseudo-crystalline templates toward mature, crystalline PbS NSs. We propose a self-induced templating mechanism based on an oleylamine-lead-thiocyanate (OLAM-Pb-SCN) complex with two Pb-SCN units as a building block; the interactions between the long-chain ligands regulate the crystal structure and possibly the lateral dimensions.

16.
Int. j. morphol ; 41(2): 505-511, abr. 2023. ilus, tab
Artículo en Español | LILACS | ID: biblio-1440296

RESUMEN

Las arterias sigmoideas son ramas de la arteria mesentérica inferior e irrigan al colon sigmoideo. Se originan del tronco de las arterias sigmoideas. Esta es la descripción más frecuente según los autores consultados. El objetivo fue analizar las variaciones en el origen y distribución de las arterias sigmoideas mediante disección. Se utilizaron 13 preparados cadavéricos formolizados al 10 %. Se disecó la cavidad abdominal para identificar a las arterias sigmoideas. Se evidenció su bifurcación paralela al colon sigmoideo. Se lo delimitó mediante reparos palpables. Patrón I: 4 casos (30,8 %). Variante de la arcada sigmoidea como rama colateral de la arteria mesentérica inferior. Tipo Ia: 1 caso (25 %). Sin asociaciones. Tipo Ib: 1 caso (25 %). Asociada al tronco sigmoideo. Tipo Ic: 2 casos (50 %). Asociada a arterias sigmoideas accesorias. Patrón II: 6 casos (46,2 %). Variante del tronco común entre arteria cólica izquierda y arterias destinadas al colon sigmoideo. Tipo IIa: 3 casos (50 %). Sin asociaciones. Tipo IIb: 2 casos (33,3 %). Asociado al tronco sigmoideo. Tipo IIc: 1 caso (16,7 %). Asociado a arterias sigmoideas accesorias. Patrón III: 3 casos (23 %). Variante clásica. Se definió por la ausencia del tronco común con la arteria cólica izquierda y de la arcada sigmoidea. Tipo IIIa: 2 casos (66,7 %). Un número variable de arterias sigmoideas nacen como ramas colaterales de la arteria mesentérica inferior, sin asociarse al tronco sigmoideo. Tipo IIIb: 1 caso (33,3 %). La arteria cólica izquierda emite como rama colateral la primera arteria sigmoidea y se asocia al tronco sigmoideo. 1. El patrón II es el prevalente en este trabajo (46,2 %). 2. La variante clásica no es la predominante en esta investigación (23 %). 3. La arcada sigmoidea tiene 53,8 % de incidencia.


SUMMARY: The sigmoid arteries are branches of the inferior mesenteric artery and supply the sigmoid colon. They originate from the trunk of the sigmoids. This is the most frequent description according to the consulted authors. The objective is to analyze the variations in the origin and distribution of the sigmoid arteries through dissection. 13 cadaveric preparations formalized at 10 % and instruments were used. The abdominal cavity was dissected to identify the sigmoid arteries. Its bifurcation parallel to the sigmoid colon is evident. It is delimited by palpable repairs. Pattern I: 4 cases (30.8 %). Variant of the sigmoid arcade as a collateral branch of the inferior mesenteric artery. Type Ia: 1 case (25 %). No associations. Type Ib: 1 case (25 %). Associated with the sigmoid trunk. Type Ic: 2 cases (50 %). Associated with accessory sigmoid arteries. Pattern II: 6 cases (46.2 %). Variant of the common trunk between the left colic artery and arteries destined for the sigmoid colon. Type IIa: 3 cases (50 %). No associations. Type IIb: 2 cases (33.3 %). Associated with the sigmoid trunk. Type IIc: 1 case (16.7 %). Associated with accessory sigmoid arteries. Pattern III: 3 cases (23 %). Classic variant. It was defined by the absence of the common trunk with the left colic artery and the sigmoid arcade. Type IIIa: 2 cases (66.7 %). A variable number of sigmoid arteries arise as collateral branches of the inferior mesenteric artery, without being associated with the sigmoid trunk. Type IIIb: 1 case (33.3 %). The left colic artery gives off the first sigmoid artery as a collateral branch and is associated with the sigmoid trunk. 1. Pattern II is the most prevalent in this study (46.2 %). 2. The classic variant is not the predominant one in this research (23 %). 3. The sigmoid arcade has a 53.8 % incidence.


Asunto(s)
Humanos , Masculino , Femenino , Colon Sigmoide/irrigación sanguínea , Arteria Mesentérica Inferior/anatomía & histología , Cadáver
17.
Small ; 19(12): e2206712, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36650930

RESUMEN

Out-of-equilibrium self-assembly of metal nanoparticles (NPs) has been devised using different types of strategies and fuels, but achieving finite 3D structures with a controlled morphology through this assembly mode is still rare. Here, a spherical peptide-gold superstructure (PAuSS) is used as a template to control the out-of-equilibrium self-assembly of Au NPs, obtaining a transient 3D-branched Au-nanoshell (BAuNS) stabilized by sodium dodecyl sulphate (SDS). The BAuNS dismantles upon SDS concentration gradient equilibration over time in the sample solution, leading to NPs disassembly and regression to PAuSS. Notably, BAuNS assembly and disassembly promotes temporary interparticle plasmonic coupling, leading to reversible and tunable changes of their plasmonic properties, a highly desirable behavior in the development of optoelectronic nanodevices.

18.
Nano Lett ; 23(1): 58-65, 2023 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-36584282

RESUMEN

Immunoassays exploiting magnetization dynamics of magnetic nanoparticles are highly promising for mix-and-measure, quantitative, and point-of-care diagnostics. However, how single-core magnetic nanoparticles can be employed to reduce particle concentration and concomitantly maximize assay sensitivity is not fully understood. Here, we design monodisperse Néel and Brownian relaxing magnetic nanocubes (MNCs) of different sizes and compositions. We provide insights into how to decouple physical properties of these MNCs to achieve ultrahigh sensitivity. We find that tricomponent-based Zn0.06Co0.80Fe2.14O4 particles, with out-of-phase to initial magnetic susceptibility χ″/χ0 ratio of 0.47 out of 0.50 for magnetically blocked ideal particles, show the ultrahigh magnetic sensitivity by providing a rich magnetic particle spectroscopy (MPS) harmonics spectrum despite bearing lower saturation magnetization than dicomponent Zn0.1Fe2.9O4 having high saturation magnetization. The Zn0.06Co0.80Fe2.14O4 MNCs, coated with catechol-based poly(ethylene glycol) ligands, measured by our benchtop MPS show 3 orders of magnitude better particle LOD than that of commercial nanoparticles of comparable size.


Asunto(s)
Nanopartículas de Magnetita , Nanopartículas , Nanopartículas de Magnetita/química , Magnetismo , Campos Magnéticos , Fenómenos Físicos , Análisis Espectral , Nanopartículas/química
19.
Cancers (Basel) ; 14(17)2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-36077644

RESUMEN

Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.

20.
Blood Adv ; 6(18): 5395-5402, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-35675590

RESUMEN

Promising results have been shown with the combination of ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The PONALFIL (Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia) trial combined ponatinib (30 mg/d) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ ALL patients aged 18 to 60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary end points were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age, 49 years; range, 19-59 years) entered the trial. All exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only 1 patient died (of graft-versus-host disease), and 5 patients exhibited molecular relapse after alloHSCT. No tyrosine kinase inhibitor was given after HSCT in 18 of 26 patients. Twenty-nine patients are alive (median follow-up, 2.1 years; range, 0.2-4.0 years), with 3-year EFS and overall survival (OS) of 70% (95% confidence interval, 51-89) and 96% (95% confidence interval, 89-100), respectively. Comparison of the PONALFIL and the ALLPh08 (Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph [BCR-ABL] Positive; same schedule, using imatinib as the tyrosine kinase inhibitor) trials by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS, 96% vs 53%; P = .002). The most frequent grade 3 to 4 adverse events were hematologic (42%), infectious (17%), and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ ALL. Cross-trial comparison suggests improvement vs imatinib (clinicaltrials.gov identifier #NCT02776605).


Asunto(s)
Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Humanos , Mesilato de Imatinib/uso terapéutico , Imidazoles , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Piridazinas , Recurrencia , Adulto Joven
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