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1.
Ann Hematol ; 102(10): 2909-2922, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37052663

RESUMEN

Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC) of the test and first doses, respectively, targeting a total AUC of 82.1 mg·h/L. All patients received either BU and cyclophosphamide conditioning (BU/CY) or fludarabine (FLU)-containing conditioning. The BU clearance at the first dose decreased more in patients receiving FLU than in those receiving BU/CY; however, BU clearance also declined over time in patients who received BU/CY. The simulated total AUC (sAUC) with test dose only was significantly higher in patients who received FLU than in those who received BU/CY, but sAUC with the combined strategy was comparable. The 100-day progression-free survival was 85.5% (95% confidence interval [CI]: 71.9-92.8%), and was not inferior to that in the fixed-dose group. For the FLU-containing regimens, the PK-guided group showed decreased relapse (0.0% vs. 26.9%, p = 0.03), and favorable overall survival (75.1% vs. 57.0%, p = 0.07) at 1 year. The combined strategy effectively controlled the BU exposure close to the target levels, potentially improving efficacy, especially in patients receiving the FLU-containing regimen. Clinical evaluation of efficacy of dose-modified intravenous busulfan in allogeneic hematopoietic stem cell transplantation for hematological malignancy (#UMIN000014077, June 15th, 2014).


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Busulfano , Ciclofosfamida , Monitoreo de Drogas , Neoplasias Hematológicas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Acondicionamiento Pretrasplante , Vidarabina
2.
Phys Rev Lett ; 126(1): 015901, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33480802

RESUMEN

We report measurements of the thermal Hall effect in single crystals of both pristine and isotopically substituted strontium titanate. We discovered a 2 orders of magnitude difference in the thermal Hall conductivity between SrTi^{16}O_{3} and ^{18}O-enriched SrTi^{18}O_{3} samples. In most temperature ranges, the magnitude of thermal Hall conductivity (κ_{xy}) in SrTi^{18}O_{3} is proportional to the magnitude of the longitudinal thermal conductivity (κ_{xx}), which suggests a phonon-mediated thermal Hall effect. However, they deviate in the temperature of their maxima, and the thermal Hall angle ratio (|κ_{xy}/κ_{xx}|) shows anomalously decreasing behavior below the ferroelectric Curie temperature T_{c}∼25 K. This observation suggests a new underlying mechanism, as the conventional scenario cannot explain such differences within the slight change in phonon spectrum. Notably, the difference in magnitude of thermal Hall conductivity and rapidly decreasing thermal Hall angle ratio in SrTi^{18}O_{3} is correlated with the strength of quantum critical fluctuations in this displacive ferroelectric. This relation points to a link between the quantum critical physics of strontium titanate and its thermal Hall effect, a possible clue to explain this example of an exotic phenomenon in nonmagnetic insulating systems.

3.
Inorg Chem ; 60(6): 4068-4075, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33661608

RESUMEN

In this paper, a comparative structural, dielectric, and magnetic study of two langasite compounds Ba3TeCo3P2O14 (absence of lone pair) and Pb3TeCo3P2O14 (Pb2+ 6s2 lone pair) have been carried out to precisely explore the development of room temperature spontaneous polarization in the presence of a stereochemically active lone pair. In the case of Pb3TeCo3P2O14, mixing of both Pb 6s with Pb 6p and O 2p helps the lone pair to be stereochemically active. This stereochemically active lone pair brings a large structural distortion within the unit cell and creates a polar geometry, while the Ba3TeCo3P2O14 compound remains in a nonpolar structure due to the absence of any such effect. Consequently, polarization measurement under varying electric fields confirms room temperature ferroelectricity for Pb3TeCo3P2O14, which was not the case for Ba3TeCo3P2O14. A detailed study was carried out to understand the microscopic mechanism of ferroelectricity, which revealed the exciting underlying activity of a polar TeO6 octahedral unit as well as Pb-hexagon.

4.
Inorg Chem ; 60(1): 225-230, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33320663

RESUMEN

GaFeO3-type iron oxides are promising multiferroics due to the coexistence of large spontaneous magnetization and polarization near room temperature. However, the high leakage current and difficulties associated with synthesizing single crystals make it difficult to achieve two important features in the system: a large ferroelectric polarization switching and magnetoelectric coupling at a high-temperature region. Herein, we report successful achievement of these features by preparing high-quality Sc-doped GaFeO3 single crystals (ScxGa1-x/2Fe1-x/2O3 with x = 0-0.3) using the floating zone method. The x ≥ 0.05 crystals exhibit a leakage current 104 times lower than the x = 0 crystals, highlighting the importance of Sc doping. Because of the reduced leakage current, the Sc-doped crystals exhibit large ferroelectric polarization switching along the c-axis with a remanent polarization of 22-25 µC/cm2, which is close to the theoretically predicted polarization value of 25-28 µC/cm2. In addition, the Sc-doped crystals exhibit ferrimagnetism with magnetic anisotropy along the a-axis. Furthermore, a magnetic-field-induced modulation of polarization is observed in the x = 0.15 crystal even at a relatively high temperature, i.e., 100 K.

5.
Biol Blood Marrow Transplant ; 26(12): 2346-2358, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32738500

RESUMEN

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the key strategy to cure patients with mature T and natural killer (NK) cell lymphomas/leukemia, especially those with relapsed/refractory diseases, there is no consensus strategy for donor selection. We retrospectively analyzed the outcomes of allo-HSCT in 111 patients in 15 Japanese institutions as a multi-institutional joint research project. Thirty-nine patients received bone marrow or peripheral blood stem cell transplantation from related donors (rBMT/rPBSCT), 37 received BMT/PBSCT from unrelated donors (uBMT/uPBSCT), and 35 received cord blood transplantation (CBT). Overall survival (OS) and progression-free survival (PFS) at 4 years were 42% and 34%, respectively. The cumulative incidences of relapse and nonrelapse mortality were 43% and 25%. In multivariate analysis, CBT showed comparable OS with rBMT/rPBSCT (rBMT/rPBSCT versus CBT: hazard ratio [HR], 1.63; P = .264) and better OS compared with uBMT/uPBSCT (HR, 2.99; P = .010), with a trend toward a lower relapse rate (rBMT/rPBSCT versus CBT: HR, 2.60; P = .010; uBMT/uPBSCT versus CBT: HR, 2.05; P = .082). This superiority of CBT was more definite in on-disease patients (OS: rBMT/rPBSCT versus CBT: HR, 5.52; P = .021; uBMT/uPBSCT versus CBT: HR, 6.80; P = .007). Better disease control was also strongly associated with better OS and PFS with lower relapse rate. In conclusion, allo-HSCT is beneficial for the survival of patients with mature T and NK cell lymphomas/leukemia if performed in a timely fashion. Since CBT showed favorable survival with a lower relapse risk, it could be a preferred alternative, especially in on-disease patients.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Trasplante de Médula Ósea , Humanos , Células Asesinas Naturales , Estudios Retrospectivos , Linfocitos T
6.
Alcohol Clin Exp Res ; 44(11): 2275-2282, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32890420

RESUMEN

BACKGROUND: Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known deterrent to the development of alcohol use disorder (AUD), and however, some individuals with inactive ALDH2 do go on to develop AUD. These alcoholics are likely to have strong risk factors for the development of this disorder. Using a model of alcoholics with inactive ALDH2 (the AIA model), we investigated the unique characteristics of alcoholics with inactive ALDH2 in an attempt to identify the risk factors for AUD. In this study, we focused on comorbid psychiatric and personality disorders as potential risk factors for AUD. METHODS: The subjects were 103 male alcoholics with inactive ALDH2 (AIAs), 87 age- and ADH1B genotype-matched alcoholics with active ALDH2 (AAAs) and 200 age-matched healthy men. The alcoholics were divided into 4 subgroups according to their ALDH2 and ADH1B genotypes (inactive ALDH2 vs. active ALDH2, usual ADH1B vs. superactive ADH1B). To assess the participants' comorbid psychiatric disorders, we conducted semi-structured interviews using the Japanese translation of SSAGA version 2. We compared the prevalence of comorbid psychiatric and personality disorders among groups with different combinations of the ALDH2 and ADH1B genotypes. RESULTS: The prevalence of attention-deficit/hyperactivity disorder (ADHD) was significantly higher in the AIAs with usual ADH1B than in the other 3 subgroups of alcoholics. In contrast, the prevalence rates of agoraphobia and panic disorder were significantly lower in the AIAs with superactive ADH1B than in the other 3 subgroups of alcoholics. CONCLUSIONS: This study suggested that (i) ADHD is a risk factor for AUD, consistent with previous reports; (ii) agoraphobia and panic disorder may have deterrent effects against the development of AUD in individuals with inactive ALDH2, probably attributable to the similarity between the symptoms of agoraphobia and panic disorder and the adverse reactions to consumption of alcohol in subjects with inactive ALDH2.


Asunto(s)
Alcohol Deshidrogenasa/genética , Alcoholismo/etiología , Aldehído Deshidrogenasa Mitocondrial/genética , Trastornos Mentales/complicaciones , Alcoholismo/genética , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Humanos , Masculino , Trastornos Mentales/genética , Persona de Mediana Edad , Factores de Riesgo
7.
Inorg Chem ; 59(13): 8744-8748, 2020 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-32506904

RESUMEN

Zn-deficient spinel-type ZnGa2O4:Mn2+ phosphor thin films were prepared using pulsed laser deposition. With an increase (decrease) in the Zn deficiency (concentration) of the films, changes in lattice constant, optical band gap, and photoluminescence spectra were observed. All films without γ-Ga2O3:Mn showed green luminescence attributable to the transition from the 4T1 state to the 6A1 state. In addition, the spectral shape changed depending on the temperature. The luminescence spectra have two peaks resulting from the Mn2+ ions located in the tetrahedral and octahedral sites. These peaks had different thermal quenching temperatures, which were around 320 and 260 K, respectively. Therefore, the spectral shape changed with increasing temperature. The spectral shape also depended on the Zn concentration. With an increase (decrease) in the Zn concentration (deficiency) of the films, the intensity of emission from Td increased in comparison with that from Oh. Therefore, the position of Mn2+ was controlled by Zn deficiency similarly to the effect of crystal-site engineering.

8.
Inorg Chem ; 59(7): 4357-4365, 2020 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-32186859

RESUMEN

ε-Fe2O3, a metastable phase of iron oxide, is widely known as a room-temperature multiferroic material or as a superhard magnet. Element substitution into ε-Fe2O3 has been reported in the literature; however, the substituted ions have a strong site preference depending on their ionic radii and valence. In this study, in order to characterize the crystal structure and magnetic properties of ε-Fe2O3 in the Fe2+/Fe3+ coexisting states, Li+ was electrochemically inserted into ε-Fe2O3 to reduce Fe3+. The discharge and charge of Li+ into/from ε-Fe2O3 revealed that Li+ insertion was successful. X-ray magnetic circular dichroism results indicated that the reduced Fe did not exhibit site preference. Increasing the Li+ content in ε-Fe2O3 resulted in decreased saturation magnetization and irregular variation of the coercive field. We present a comprehensive discussion of how magnetic properties are modified with increasing Li+ content using transmission electron microscopy images and considering the Li+ diffusion coefficient. The results suggest that inserting Li+ into crystalline ε-Fe2O3 is a useful tool for characterizing crystal structure, lithiation limit, and magnetic properties in the coexistence of Fe2+/Fe3+.

9.
Inorg Chem ; 59(16): 11749-11756, 2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32799500

RESUMEN

Spontaneous polarization (Ps) of novel order-disorder type lead-free ferroelectric CaMnTi2O6 was successfully enhanced by partial V4+ substitution for Ti4+. A synchrotron X-ray diffraction study revealed that the polar displacement of octahedrally coordinated (Ti, V) in CaMn(Ti1-xVx)2O6 (0 ≤ x ≤ 0.4) increases with V4+ substitution having Jahn-Teller activity owing to the d1 electronic configuration. Our magnetic study suggested the presence of antisite disorder between Ca2+ and square planar coordinated Mn2+ associated with Mn-V intermetallic charge transfer for x ≥ 0.4, resulting in decreases in spontaneous polarization and the ferroelectric-paraelectric transition temperature. This is the first report on the enhanced polarization owing to the Jahn-Teller distortion of V4+ without stereochemical Pb2+ or Bi3+.

10.
Nano Lett ; 19(3): 1688-1694, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30759986

RESUMEN

Nanodot BaTiO3 supported LiCoO2 cathode thin films can dramatically improve high-rate chargeability and cyclability. The prepared BaTiO3 nanodot is <3 nm in height and 35 nm in diameter, and its coverage is <5%. Supported by high dielectric constant materials on the surface of cathode materials, Li ion (Li+) can intercalate through robust Li paths around the triple-phase interface consisting of the dielectric, cathode, and electrolyte. The current concentration around the triple-phase interface is observed by the finite element method and is in good agreement with the experimental data. The interfacial resistance between the cathode and electrolyte with nanodot BaTiO3 is smaller than that without nanodot BaTiO3. The decomposition of the organic solvent electrolyte can prevent the fabrication of a solid electrolyte interface around the triple-phase interface. Li+ paths may be created at non solid electrolyte interface covered regions by the strong current concentration originating from high dielectric constant materials on the cathode. Robust Li+ paths lead to excellent chargeability and cyclability.

11.
Ann Hematol ; 98(12): 2815-2823, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31713653

RESUMEN

Allogeneic hematopoietic stem cell transplantation (allo-SCT) has been considered as a potentially curative treatment option for refractory or relapsed diffuse large B cell lymphoma (DLBCL) patients. However, there is little information available, especially for Japanese patients and in cord blood transplantation (CBT). We aimed to determine treatment outcomes of allo-SCT for DLBCL in the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group. Sixty-eight DLBCL patients who underwent their first allo-SCT between 2003 and 2016 were included. The median time from diagnosis to transplantation was 13.5 months. Thirty-one patients were in CR/PR at transplantation. Twenty-seven patients underwent CBT. The median follow-up for survivors was 44.2 months. Four-year overall survival (OS) and relapse-free survival (RFS) rates were 23% (95% CI, 13-35%) and 20% (95% CI, 11-31%), respectively. Cumulative incidences of non-relapse mortality and relapse were 23% and 57%, respectively. Patients in CR/PR at allo-SCT had better OS (4-year, 46% vs 4%, P < 0.001) and RFS (4-year, 36% vs 7%, P = 0.005). The source of the stem cell did not significantly affect OS (4-year, bone marrow vs cord blood vs peripheral blood, 28.6% vs 27.2% vs 6.5%, P = 0.193). In multivariate analysis, non-remission status at SCT associated with inferior OS and RFS. Duration from diagnosis to transplantation of less than 1 year associated with inferior RFS. Allo-SCT, including CBT, may be a promising therapeutic modality for DLBCL patients who have good disease control at transplantation.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Linfoma de Células B Grandes Difuso , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia
12.
Inorg Chem ; 58(24): 16752-16760, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31774662

RESUMEN

Perovskite-type oxynitride BaTaO2N has been attracting attention for its large dielectric constant, which is almost independent of the temperature by measurements on its ceramics. Its dielectric characteristics are attributed to polar nanoregions (PNRs) in the average cubic crystal structure. Polarization saturation to produce a butterfly-like piezoresponse force microscopy (PFM) signal was observed on BaTaO2N crystals in the present study. Reddish crystallites of BaTaO2N of up to 3.1 µm in size were grown using a BaCN2 flux. Grain growth proceeded through the formation of a Ruddlesden-Popper-type oxynitride from the reaction between BaTaO2N powder and molten BaCN2. Their electrical property was studied using PFM with special care because of the small size of the crystals. They were found to be much more highly insulating than its ceramics. Ferroelectricity with complete phase inversion was observed on an oxynitride perovskite crystal for the first time. A large coercivity of 50-60 V was observed in the measurement. Such ferroelectricity is ascribed to the PNRs induced by the polar linkages between cis-type TaO4N2 octahedra.

13.
Rinsho Ketsueki ; 60(2): 106-111, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-30842376

RESUMEN

A 64-year-old man presented to the emergency department with sudden-onset upper abdominal pain and pain in the left chest area. His platelet count was 121.7×104/µl. Computed tomography (CT) showed bilateral adrenal swelling and inflammation of the adjacent tissue. Diffusion-weighted magnetic resonance imaging (MRI) showed hyperintensity in the bilateral adrenal glands. The patient was diagnosed with bilateral adrenal infarction. A bone marrow biopsy yielded a diagnosis of essential thrombocythemia, and a positive JAK2 V617F mutation was detected. He presented with recurrent adrenal infarction and developed aortic mural thrombosis and splenic infarction. We administered aspirin and performed cytoreductive therapy with hydroxyurea and anagrelide; however, the patient then went into heart failure resulting from coronary artery stenosis. We then added prasugrel to the list of medicines administered to manage his condition. Bilateral adrenal infarction is a very rare thrombotic event of essential thrombocythemia. CT and MRI were useful for making the diagnosis; however, we also had to rule out acute coronary syndrome or intestinal ischemia. Our patient presented with strong thrombotic diathesis, which prompted us to use dual antiplatelet therapy; however, further studies are needed to confirm the efficacy and safety of this treatment.


Asunto(s)
Enfermedades de las Glándulas Suprarrenales/diagnóstico , Infarto/diagnóstico , Trombocitemia Esencial/diagnóstico , Enfermedades de las Glándulas Suprarrenales/etiología , Glándulas Suprarrenales/patología , Anciano , Aspirina , Humanos , Hidroxiurea , Infarto/etiología , Masculino , Trombocitemia Esencial/complicaciones , Trombosis/etiología
14.
Transfusion ; 58(12): 2773-2776, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30265752

RESUMEN

BACKGROUND: Donor-specific human leukocyte antigen (HLA) antibodies are a significant risk factor for graft failure in cord blood transplantation (CBT). Although there are several treatments to decrease HLA antibodies, such as platelet transfusion, plasma exchange, rituximab, and bortezomib, their effectiveness has not been established. STUDY DESIGN AND METHODS: We herein report the case of a primary myelofibrosis (PMF) patient with broad HLA antibodies who underwent CBT from an HLA-homozygous donor in which the alleles were matched only in the host-versus-graft direction (homo-to-hetero CBT). RESULTS: The cord blood was killer cell immunoglobulin-like receptor (KIR) ligand matched. She received a reduced-intensity conditioning regimen. We used tacrolimus and mycophenolate mofetil as prophylaxis against graft-versus-host disease (GVHD). The neutrophils engrafted on Day 31. A chimerism analysis with fluorescence in situ hybridization of peripheral blood cells showed 99.9% donor type on Day 33. She developed only mild acute skin GVHD and chronic skin GVHD. CONCLUSION: This case indicates the usefulness of homo-to-hetero CBT in a patient with broad HLA antibodies with a strong mean fluorescence intensity, which is a significant risk factor for graft failure. Further studies are necessary to determine the risk of GVHD and to elucidate the association between KIR ligand incompatibility and graft failure in homo-to-hetero CBT.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Supervivencia de Injerto , Prueba de Histocompatibilidad , Isoanticuerpos , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/terapia , Adulto , Aloinjertos , Femenino , Humanos
16.
RSC Adv ; 14(20): 13900-13904, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38699686

RESUMEN

Since the discovery of ferroelectricity in a wurtzite-type structure, this structural type has gathered much attention as a next-generation ferroelectric material due to its high polarization value combined with its high breakdown strength. However, the main targets of wurtzite-type ferroelectrics have been limited thus far to simple nitride/oxide compounds. The investigation of new ferroelectric materials with wurtzite-type structures is important for understanding ferroelectricity in such structures. We therefore focus on ß-LiGaO2 in this study. Although AlN and ZnO possess well-known wurtzite-type structures (P63mc), ß-LiGaO2 has a distorted wurtzite-type structure (Pna21), and there are no reports of ferroelectricity in LiGaO2. In this study, we have revealed that LiGaO2 exhibits relatively high barrier height energy for polarization switching, however, Sc doping effectively reduces that energy. Then, we conducted thin film preparation and evaluation for Sc-doped LiGaO2 to observe its ferroelectric properties. We successfully observed ferroelectric behavior by using piezoresponse force microscopy measurements for LiGa0.8Sc0.2O2/SrRuO3/(111)SrTiO3.

17.
Transplant Cell Ther ; 29(5): 332.e1-332.e11, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36796517

RESUMEN

The alkylating agent busulfan is commonly used as conditioning in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). However, a consensus has not yet been reached regarding the optimal busulfan dose in cord blood transplantation (CBT). Therefore, we conducted this large nationwide cohort study to retrospectively analyze the outcomes of CBT in patients with AML receiving busulfan at intermediate (6.4 mg/kg i.v.; BU2) or higher (12.8 mg/kg i.v.; BU4) doses within a fludarabine/i.v. busulfan (FLU/BU) regimen. Among 475 patients who underwent their first CBT following FLU/BU conditioning between 2007 and 2018, 162 received BU2 and 313 received BU4. Multivariate analysis identified BU4 as a significant factor for longer disease-free survival (hazard ratio [HR], .85; 95% confidence interval [CI], .75 to .97; P = .014) and a lower relapse rate (HR, .84; 95% CI, .72 to .98; P = .030). No significant differences were observed in non-relapse mortality between BU4 and BU2 (HR, 1.05; 95% CI, .88-1.26; P = .57). Subgroup analyses showed that BU4 provided significant benefits for patients who underwent transplantation while not in complete remission (CR) and those age <60 years. Our present results suggest that higher busulfan doses are preferable in patients undergoing CBT, particularly those not in CR and younger patients.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Persona de Mediana Edad , Busulfano/uso terapéutico , Estudios de Cohortes , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Recurrencia
18.
Cell Transplant ; 32: 9636897231194497, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37646153

RESUMEN

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/farmacología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Acondicionamiento Pretrasplante , Estudios Retrospectivos
19.
Transplant Cell Ther ; 29(6): 347.e1-347.e11, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36889508

RESUMEN

Cord blood transplantation (CBT) is an attractive therapeutic option for patients with hematologic malignancies. CBT tolerates HLA mismatches between donors and recipients, but the HLA mismatches that generate graft-versus-tumor (GVT) effects remain unknown. Given that HLA molecules contain epitopes comprising polymorphic amino acids that determine their immunogenicity, we investigated associations between epitope-level HLA mismatches and relapse following single-unit CBT. A total of 492 patients with hematologic malignancies who underwent single-unit, T cell-replete CBT were included in this multicenter retrospective study. HLA epitope mismatches (EMs) were quantified using HLA matchmaker software from donor and recipient HLA-A, -B, -C, and -DRB1 allele data. Patients were dichotomized by median EM value and divided into 2 groups: patients who underwent transplantation in complete/partial remission (standard stage: 62.4%) and others (advanced stage: 37.6%). The median number of EMs in the graft-versus-host direction (GVH-EM) was 3 (range, 0 to 16) at HLA class I and 1 (range, 0 to 7) at HLA-DRB1. Higher HLA class I GVH-EM was associated with increased nonrelapse mortality (NRM) in the advanced stage group (adjusted hazard ratio [HR], 2.12; P = .021), with no significant advantage for relapse in either stage. In contrast, higher HLA-DRB1 GVH-EM was associated with better disease-free survival in the standard stage group (adjusted HR, .63; P = .020), which was attributed to lower relapse risk (adjusted HR, .46; P = .014). These associations also were observed even within HLA-DRB1 allele-mismatched transplantations in the standard stage group, indicating that EM might have an impact on relapse risk independent of allele mismatch. High HLA-DRB1 GVH-EM did not increase NRM in either stage. High HLA-DRB1 GVH-EM may lead to potent GVT effects and a favorable prognosis following CBT, especially in patients who underwent transplantation at the standard stage. This approach may facilitate appropriate unit selection and improve the overall prognosis of patients with hematologic malignancies who undergo CBT.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Humanos , Cadenas HLA-DRB1/genética , Epítopos/genética , Estudios Retrospectivos , Prueba de Histocompatibilidad , Recurrencia Local de Neoplasia/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia
20.
Phys Rev Lett ; 109(19): 197601, 2012 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-23215426

RESUMEN

We report the high-resolution and broadband light-scattering spectroscopy of a single crystal of a prototypical relaxor ferroelectric, Pb(Mg(1/3)Nb(2/3))O(3). A self-similar broad central peak, whose intensity is expressed as I(ω) [Symbol: see text] ω(α) has been observed, indicating the presence of a fractal in the crystal. A strong correspondence exists between the temperature dependence of the exponent α and that of the reported behaviors of polar nanoregions. The estimated fractal dimension (d(f) ≈ 2.6) at low temperatures clearly indicates a percolation transition of the polar nanoregions at around 240 K.

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