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BACKGROUND: Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand. PATIENTS AND METHODS: The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of ≥65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP. RESULTS: A total of 836 patients with a median age of 74 years (range, 65-96 years) were analyzed. In the SoLT-J cohort (n = 555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score ≥3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort (n = 281). CONCLUSION: The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP. The Oncologist 2017;22:554-560 IMPLICATIONS FOR PRACTICE: Currently, little is known regarding how to identify elderly patients with diffuse large B-cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host-dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Avaliação Geriátrica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Comorbidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Hipoalbuminemia/induzido quimicamente , Hipoalbuminemia/patologia , Japão , Linfoma Difuso de Grandes Células B/patologia , Masculino , Medicina de Precisão , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Fatores de Risco , Rituximab , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
We develop a single two-layered model framework that captures and replicates both the statistical properties of the network as well as those of the intrinsic quantities of the agents. Our model framework consists of two distinct yet connected elements that were previously only studied in isolation, namely methods related to temporal network structures and those associated with money transport flows. Within this context, the network structure emerges from the first layer and its topological structure is transferred to the second layer associated with the money transactions. In this manner, we can explain how the micro-level dynamics of the agents within the network lead to the exogenous manifestation of the aggregated system statistical data en-wrapping the very same agents within the system. This is done by capturing the essential dynamics of collective motion in complex networks that enable the simultaneous emergence of tent-shaped distributions in growth rates within the agents, together with the emergence of scaling properties within the network in the study. We can validate the model framework and dynamics by applying these to the context of the real-world inter-firm trading network of firms in Japan and comparing the results of the statistical distributions at both network and agent levels in a temporal manner. In particular, we compare our results to the fundamental quantities supporting the seven empirical laws observed in data: the degree distribution, the mean degree growth rate over time, the age distribution of the firms, the preferential attachment, the sales distribution in steady states, their growth rates, their scaling relations generated by the model. We find these results to be nearly identical to the real-world data. The framework has the potential to be transformed into a forecasting tool to support decision-makers on financial and prudential policies.
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During the COVID-19 pandemic, governments faced difficulties in implementing mobility restriction measures, as no clear quantitative relationship between human mobility and infection spread in large cities is known. We developed a model that enables quantitative estimations of the infection risk for individual places and activities by using smartphone GPS data for the Tokyo metropolitan area. The effective reproduction number is directly calculated from the number of infectious social contacts defined by the square of the population density at each location. The difference in the infection rate of daily activities is considered, where the 'stay-out' activity, staying at someplace neither home nor workplace, is more than 28 times larger than other activities. Also, the contribution to the infection strongly depends on location. We imply that the effective reproduction number is sufficiently suppressed if the highest-risk locations or activities are restricted. We also discuss the effects of the Delta variant and vaccination.
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COVID-19 , Humanos , COVID-19/epidemiologia , Número Básico de Reprodução , SARS-CoV-2 , PandemiasRESUMO
Owing to the big data the extension of physical laws on nonmaterial has seen numerous successes, and human mobility is one of the scientific frontier topics. Recent GPS technology has made it possible to trace detailed trajectories of millions of people, macroscopic approaches such as the gravity law for human flow between cities and microscopic approaches of individual origin-destination distributions are attracting much attention. However, we need a more general basic model with wide applicability to realize traffic forecasting and urban planning of metropolis fully utilizing the GPS data. Here, based on a novel idea of treating moving people as charged particles, we introduce a method to map macroscopic human flows into currents on an imaginary electric circuit defined over a metropolitan area. Conductance is found to be nearly proportional to the maximum current in each location and synchronized human flows in the morning and evening are well described by the temporal changes of electric potential. Surprisingly, the famous fluctuation-dissipation theorem holds, namely, the variances of currents are proportional to the conductivities akin to an ordinary material.
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Urbanização , Cidades , Sistemas de Informação Geográfica , HumanosRESUMO
We discovered a D-phenylserine deaminase that catalyzed the pyridoxal 5'-phosphate (PLP)-dependent deamination reaction from D-threo-phenylserine to phenylpyruvate in newly isolated Arthrobacter sp. TKS1. The enzyme was partially purified, and its N-terminal amino acid sequence was analyzed. Based on the sequence information, the gene encoding the enzyme was identified and expressed in Escherichia coli. The expressed protein was purified to homogeneity and characterized. The enzyme consisted of two identical 46-kDa subunits and showed maximum activity at pH 8.5 and 55°C. The enzyme was stable in the range of pH 7.5 to pH 8.5 and up to 50°C. The enzyme acted on the D-forms of ß-hydroxy-α-amino acids, such as D-threo-phenylserine (K(m), 19 mM), D-serine (K(m), 5.8 mM), and D-threonine (K(m), 102 mM). As L-threonine, D-allo-threonine, L-allo-threonine, and DL-erythro-phenylserine were inert, the enzyme could distinguish D-threo-form from among the four stereoisomers of phenylserine or threonine. The enzyme was activated by ZnSO(4), CuSO(4), BaCl(2), and CoCl(2) and strongly inhibited by phenylhydrazine, sodium borohydride, hydroxylamine, and DL-penicillamine. The enzyme exhibited absorption maxima at 280 and around 415 nm. The enzyme has an N-terminal domain similar to that of alanine racemase, which belongs to the fold type III group of pyridoxal enzymes.
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Arthrobacter/enzimologia , Proteínas de Bactérias/química , Liases/química , Serina/análogos & derivados , Sequência de Aminoácidos , Arthrobacter/química , Arthrobacter/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Estabilidade Enzimática , Cinética , Liases/genética , Liases/metabolismo , Dados de Sequência Molecular , Peso Molecular , Estrutura Terciária de Proteína , Alinhamento de Sequência , Serina/metabolismo , Especificidade por SubstratoRESUMO
Methods for effectively utilizing lignin are necessary for the realization of a sustainable society. Herein, we report a method for directly converting lignin to graphene-based materials. Fe-supported lignin is prepared by dissolving lignin in an aqueous FeCl2 solution, followed by freeze drying. Graphene is then produced by catalytically carbonizing this Fe-supported lignin at 1200 °C. The characteristics of both the Fe catalyst and lignin are crucial for the production of high-quality graphene. Specifically, the lignin should disperse well in water, freeze dry, and carbonize via solid-state carbonization. The obtained graphene-based material is highly resistant to electrochemical oxidation, as observed in other graphene-based materials. The direct conversion of lignin to graphene described herein is an unprecedented method for synthesizing large amounts of graphene-based material at low cost, as well as being an excellent use for lignin.
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We report a case of hepatosplenic T-cell lymphoma (HSTL) transplanted from an HLA-haploidentical daughter. A 51-year-old man was referred due to liver function test abnormalities and fever. He was confirmed to have γδ-type HSTL by bone marrow and liver biopsies. He was treated with five cycles of a CHOP regimen. Although metabolic complete response (CR), as defined by positron emission tomography, was achieved, his bone marrow still contained tumor cells on polymerase chain reaction (PCR). He underwent transplantation using unmanipulated peripheral blood stem cells from his HLA-haploidentical daughter. The preconditioning regimen consisted of ï¬udarabine, melphalan, busulfan and antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. Neutrophil engraftment was achieved on day 14. His bone marrow exhibited a completely female phenotype by ï¬uorescence in situ hybridization, and no lymphoma cells were detected by PCR on day 30. Although he developed grade II acute GVHD on day 47, it was successfully treated by prednisolone. He has a limited type of skin chronic GVHD and still receives oral immunosuppressive therapy. He remains in CR four years after transplantation.
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Transplante de Células-Tronco Hematopoéticas , Neoplasias Hepáticas/terapia , Linfoma de Células T/terapia , Transplante Haploidêntico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/análise , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/patologia , Linfoma de Células T/patologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Tacrolimo/uso terapêutico , Transplante Haploidêntico/métodos , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
We have constructed a synthetic ecosystem consisting of two Escherichia coli populations, which communicate bi-directionally through quorum sensing and regulate each other's gene expression and survival via engineered gene circuits. Our synthetic ecosystem resembles canonical predator-prey systems in terms of logic and dynamics. The predator cells kill the prey by inducing expression of a killer protein in the prey, while the prey rescue the predators by eliciting expression of an antidote protein in the predator. Extinction, coexistence and oscillatory dynamics of the predator and prey populations are possible depending on the operating conditions as experimentally validated by long-term culturing of the system in microchemostats. A simple mathematical model is developed to capture these system dynamics. Coherent interplay between experiments and mathematical analysis enables exploration of the dynamics of interacting populations in a predictable manner.
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Ecossistema , Escherichia coli/fisiologia , Simulação por Computador , Dimetilpolisiloxanos/química , Escherichia coli/metabolismo , Microfluídica , Modelos Biológicos , Modelos Teóricos , Oscilometria , Plasmídeos/metabolismo , Dinâmica Populacional , Crescimento Demográfico , Biologia de Sistemas , Fatores de TempoRESUMO
Herein, we synthesized P- and N-doped carbon materials (PN-doped carbon materials) through controlled phosphoric acid treatment (CPAT) of folic acid (FA) and probed their ability to catalyze the oxygen reduction reaction (ORR) at the cathode of a fuel cell. Precursors obtained by heating FA in the presence of phosphoric acid at temperatures of 400-1000 °C were further annealed at 1000 °C to afford PN-doped carbon materials. The extent of precursor P doping was maximized at 700 °C, and the use of higher temperatures resulted in activation and increased porosity rather than in increased P content. The P/C atomic ratios of PN-doped carbon materials correlated well with those of the precursors, which indicated that CPAT is well suited for the preparation of PN-doped carbon materials. The carbon material prepared using a CPAT temperature of 700 °C exhibited the highest ORR activity and was shown to contain -C-PO2 and -C-PO3 moieties as the major P species and pyridinic N as the major N species. Moreover, no N-P bonds were detected. It was concluded that the presence of -C-PO2 and -C-PO3 units decreases the work function and thus raises the Fermi level above the standard O2/H2O reduction potential, which resulted in enhanced ORR activity. Finally, CPAT was concluded to be applicable to the synthesis of PN-doped carbon materials from N-containing organic compounds other than FA.
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Carbon-based oxygen reduction reaction (ORR) catalysts are regarded as a promising candidate to replace the currently used Pt catalyst in polymer electrolyte fuel cells (PEFCs); however, the active sites remain under discussion. We predicted that warped graphitic layers (WGLs) are responsible for the ORR catalytic activity in some carbon catalysts (i.e., carbon alloy catalysts (CACs)). To prove our assumption, we needed to use WGLs consisting of carbon materials, but without any extrinsic catalytic elements, such as nitrogen, iron, or cobalt, which effectively enhance ORR activity. The present study employed a fullerene extraction residue as a starting material to construct WGLs. The oxidation of the material at 600 °C exposed the WGLs by removing the surrounding amorphous moieties. Transmission electron microscopy (TEM) observations revealed the formation of WGLs by oxidation treatment at 600 °C in an O2/N2 stream. Extending the oxidation time increased the purity of the WGL phase, but also simultaneously increased the concentration of oxygen-containing surface functional groups as monitored by temperature programmed desorption (TPD). The specific ORR activity increased with oxidation up to 1 h and then decreased with the intensive oxidation treatment. Correlations between the specific ORR activity and other parameters confirmed that the development of the WGL and the increase in the O/C ratio are the competing factors determining specific ORR activity. These results explain the maximum specific ORR activity after 1 h of oxidation time. WGLs were found to lower the heat of adsorption for O2 and to increase the occurrence of heterogeneous electron transfer.
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Objective This study retrospectively evaluated fungal dissemination due to hospital reconstruction and explored effective methods of predicting an outbreak. Methods Patients suspected of having invasive aspergillosis were tested for Aspergillus galactomannan antigen before and after reconstruction, and the mean values of three months of testing for positive patients were determined. The characteristics of patients with aspergillosis during this period were also assessed. Results Forty-five patients were positive for Aspergillus antigen (>0.5 cut-off index) from January 2013 to December 2014. Mean Aspergillus antigen values significantly increased following reconstruction (p<0.05). Three patients developed pneumonia due to Aspergillus and were diagnosed with "probable" invasive aspergillosis according to the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. We also discovered that the anteroom to contain dust was not prefabricated and a negative pressure system to remove dust was not used. After construction of the unit, no new cases of aspergillosis were diagnosed. Conclusion Many Aspergillus spores may be transiently floating during hospital reconstruction. Therefore, monthly surveillance with frequent serum galactomannan antigen testing to predict outbreaks is necessary. Surveillance of all patients in the hematology ward is especially important. Reconsideration of prophylactic antifungals may also be necessary during hospital reconstruction.
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Poluentes Atmosféricos/isolamento & purificação , Antígenos de Fungos/sangue , Aspergilose/diagnóstico , Aspergillus/imunologia , Aspergillus/isolamento & purificação , Surtos de Doenças/prevenção & controle , Mananas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental , Feminino , Galactose/análogos & derivados , Arquitetura Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Despite great progress in the development of nonprecious metal catalysts (NPMCs) over the past several decades, the performance and stability of these promising catalysts have not yet achieved commercial readiness for proton exchange membrane fuel cells (PEMFCs). Through rational design of the cathode catalyst layer (CCL), we demonstrate the highest reported performance for an NPMC-based membrane electrode assembly (MEA), achieving a peak power of 570 mW/cm2 under air. This record performance is achieved using a precommercial catalyst for which nearly all pores are <3 nm in diameter, challenging previous beliefs regarding the need for larger catalyst pores to achieve high current densities. This advance is achieved at industrially relevant scales (50 cm2 MEA) using a precommercial NPMC. In situ electrochemical analysis of the CCLs is also used to help gain insight into the degradation mechanism observed during galvanostatic testing. Overall, the performance of this NPMC-based MEA has achieved commercial readiness and will be introduced into an NPMC-based product for portable power applications.
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We report a successful case of living-donor lobar lung transplantation (LDLLT) for therapy-resistant broncho-bronchiolitis obliterans (BBO) after allogeneic hematopoietic stem cell transplantation (HSCT). Bronchiolitis obliterans (BO) is one of the late-onset noninfectious pulmonary complications that occur after allogeneic HSCT and is usually resistant to immunosuppressive therapy. A 17-year-old girl with acute lymphoblastic leukemia (ALL) had undergone allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling in 1997. Five years later, she relapsed with ALL and was treated with chemotherapy following stem cell rescue and donor lymphocyte infusion from the original BMT donor. Eight months later, BBO resistant to immunosuppressive therapies, including rituximab, developed in combination with chronic graft-versus-host disease (GVHD). In February 2004, the patient underwent LDLLT from 2 other family members who were mismatched at 3 HLA loci. The patient has been in good health for more than 30 months following LDLLT and shows no sign of BBO in the transplanted lungs, just as with other patients who have undergone lung transplantation for BO associated with chronic GVHD. LDLLT may therefore be considered a viable therapeutic option for the treatment of BO after allogeneic HSCT.
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Bronquiolite Obliterante/patologia , Bronquiolite Obliterante/cirurgia , Transplante de Células-Tronco Hematopoéticas , Doadores Vivos , Transplante de Pulmão , Adolescente , Bronquiolite Obliterante/imunologia , Bronquiolite Obliterante/fisiopatologia , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Recidiva , Transplante HomólogoRESUMO
A novel, one-step protocol for the selective synthesis of W2C nanoparticles from phosphotungstic acid (H3PW12O40), a low-cost and commercially available tungsten compound, was developed. The nanoparticles had diameters of 1-50 nm and were dispersed on a carbon substrate. The W2C nanoparticles were prepared by a simple operation sequence, involving impregnation of carbon black with H3PW12O40 followed by calcination at 1000 °C. X-ray diffraction study revealed the selective formation of the W2C phase in the samples prepared, whereas the tungsten carbide (WC) phase was present in the control prepared from H2WO4. Stable W2C nanoparticles were obtained using this method owing to the presence of phosphate at the interfaces between the W2C nanoparticles and the carbon substrates, which inhibited the diffusion of carbon atoms from the carbon substrates to the W2C nanoparticles, leading to the formation of WC. The W2C nanoparticles prepared showed an excellent catalytic activity for the hydrogen evolution reaction (HER), with low Tafel slopes of â¼50 mV/decade. The HER catalytic activity was notably high, being comparable to that of MoS2, which is a promising alternative to Pt. The present method can potentially be applied to produce highly effective, low-cost, Pt-free electrocatalysts for the HER.
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We encountered a 53-year-old man with general fatigue. Bone marrow investigations revealed an infiltration of CD20+CD5+CD23- cells and the presence of cyclin D1 lymphoid cells, leading to a diagnosis of mantle cell lymphoma, clinical stage IV. The first 2 lines of chemotherapy, CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone) and fludarabine-cyclophosphamide, produced only a transient decrease in serum lactic dehydrogenase levels, without a clinical remission. Because of the persistence of bone marrow hypoplasia, monotherapy with 375 mg/m2 rituximab was administered. The pancytopenia gradually improved, and a complete remission was obtained after 4 cycles of rituximab. The patient remains in complete remission 21 months after the third rituximab therapy for maintenance.
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Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.
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Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Doença Enxerto-Hospedeiro/terapia , Leucemia/terapia , Transfusão de Linfócitos , Transplante de Células-Tronco de Sangue Periférico , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Leucemia/complicações , Leucemia/mortalidade , Transfusão de Linfócitos/efeitos adversos , Transfusão de Linfócitos/métodos , Transfusão de Linfócitos/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Estudos Prospectivos , Recidiva , Indução de Remissão , Transplante Homólogo , Resultado do TratamentoRESUMO
Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.
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Medula Óssea/patologia , Primers do DNA/genética , Mieloma Múltiplo/diagnóstico , Neoplasia Residual/diagnóstico , Reação em Cadeia da Polimerase , Adulto , Idoso , Feminino , Genes de Cadeia Pesada de Imunoglobulina/genética , Técnicas de Preparação Histocitológica , Humanos , Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Neoplasia Residual/genética , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
Sixty-six adult patients with hematologic malignancies underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) without T cell depletion. The patients were preconditioned with a reduced intensity regimen, and tacrolimus was used for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment occurred in 60 patients (90.1%) and graft rejection in only 4 patients (6.1%). Among the 60 engrafted patients, only 5 developed severe (grade III or IV) acute GVHD. Twenty patients, including 19 relapse-free patients were alive at a median follow-up of 48 months (range 6-77 months). The overall survival (OS) at 6 years was 29.3%. The OS of 45 patients < 60 years of age was 43.6%, which was superior to that of 21 patients who were 60 years of age and older (9.5%) (P < 0.01). The OS of 11 patients from human leukocyte antigen (HLA) 1 locus-mismatched donors (63.6%) was higher than that of 28 patients from HLA 3 loci-mismatched donors (12.5%) (P < 0.01). Organ injury and infection were the main causes of mortality. Notably, immunosuppressive therapy could be successfully stopped in 9 patients transplanted from HLA 2 or 3 loci-mismatched donors with a median duration of 45 months (range 5-71 months). These data suggest that haplo-HSCT is a promising treatment for patients who need urgent allogeneic transplantation but lack HLA-identical family donors.
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Haplótipos , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Infecções por Citomegalovirus/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/uso terapêutico , Japão/epidemiologia , Contagem de Linfócitos , Subpopulações de Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto JovemRESUMO
Pt-free cathode catalysts for polymer electrolyte membrane fuel cells have been prepared by multi-step pyrolysis of FePc and PhRs, in the best of which show extensively high initial cell performance and good durability compared to other present precious-metal-free cathode catalysts to date.