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INTRODUCTION: Skeletal muscle mass is considered a prognostic factor for survival in patients with cancer. In this study, we investigated the associations between skeletal muscle mass, physical function, fatigue, and quality of life(QOL)at diagnosis in patients with hematological malignancies. METHODS: In this study, we included 27 untreated patients with newly diagnosed hematological malignancies who visited our hospital. The patients were assessed during the period from diagnosis to the start of chemotherapy. Data regarding age, white blood cell count, hemoglobin level, platelet count, and body mass index(BMI)were obtained from the patients' medical records. In addition, skeletal muscle mass index(SMI), phase angle (PhA), grip strength, knee extension strength, and short physical performance battery, brief fatigue inventory, EuroQol 5 dimensions 5-levels, and mini nutritional assessment short-form scores were calculated. RESULTS: The mean SMI value was 6.6±1.3 kg/m2(7.4±1.2 kg/m2 in men and 5.7±0.6 kg/m2 in women). SMI showed significant correlations with platelet count(r=-0.42, p=0.03), BMI(r=0.61, p≤0.01), PhA(r=0.54, p≤0.01), grip strength(r=0.81, p≤0.01), and knee extension strength(r=0.49, p=0.01). Multiple regression analysis, conducted using SMI as the dependent variable, revealed that BMI and grip strength were significant variables(p≤0.01). DISCUSSION: In untreated patients with newly diagnosed hematological malignancies, SMI was associated with BMI and grip strength but not with fatigue or QOL. Assessment of BMI and grip strength at diagnosis may help predict skeletal muscle mass.
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Neoplasias Hematológicas , Qualidade de Vida , Masculino , Humanos , Feminino , Fadiga , Hospitais , Músculo EsqueléticoRESUMO
Nucleophosmin1 (NPM1) mutations are the most frequently detected gene mutations in acute myeloid leukemia (AML) and are considered a favorable prognostic factor. We retrospectively analyzed the prognosis of 605 Japanese patients with de novo AML, including 174 patients with NPM1-mutated AML. Although patients with NPM1-mutated AML showed a high remission rate, this was not a favorable prognostic factor for overall survival (OS); this is contrary to generally accepted guidelines. Comprehensive gene mutation analysis showed that mutations in codon R882 of DNA methyltransferase 3A (DNMT3AR882 mutations) were a strong predicative factor indicating poor prognosis in all AML (p < 0.0001) and NPM1-mutated AML cases (p = 0.0020). Furthermore, multivariate analysis of all AML cases showed that DNMT3AR882 mutations and the co-occurrence of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD), NPM1 mutations, and DNMT3AR882 mutations (triple mutations) were independent factors predicting a poor prognosis related to OS, with NPM1 mutations being an independent factor for a favorable prognosis (hazard ratios: DNMT3AR882 mutations, 1.946; triple mutations, 1.992, NPM1 mutations, 0.548). Considering the effects of DNMT3AR882 mutations and triple mutations on prognosis and according to the classification of NPM1-mutated AML into three risk groups based on DNMT3AR882 /FLT3-ITD genotypes, we achieved the improved stratification of prognosis (p < 0.0001). We showed that DNMT3AR882 mutations are an independent factor for poor prognosis; moreover, when confounding factors that include DNMT3AR882 mutations were excluded, NPM1 mutations were a favorable prognostic factor. This revealed that ethnological prognostic discrepancies in NPM1 mutations might be corrected through prognostic stratification based on the DNMT3A status.
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DNA (Citosina-5-)-Metiltransferases , Leucemia Mieloide Aguda , Humanos , DNA (Citosina-5-)-Metiltransferases/genética , Análise Mutacional de DNA , Leucemia Mieloide Aguda/genética , Mutação , Nucleofosmina/genética , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Erythrocytosis, most often measured as an increase in hemoglobin and/or hematocrit, is a common reason for referral to internal medicine and hematology clinics and a rational approach is required to effectively identify patients with polycythemia vera while avoiding over-investigation. AIM: We aimed to develop and validate a simple rule to predict JAK2 mutation positivity based on complete blood count parameters to aid in the diagnostic approach to patients referred for elevated hemoglobin. SETTING: Internal medicine and hematology clinics at an academic tertiary referral center. PARTICIPANTS: The JAK2 Prediction Cohort (JAKPOT), a large retrospective cohort (n = 901) of patients evaluated by internal medicine and hematology specialists for elevated hemoglobin. DESIGN: JAK2 mutation analysis was performed in all patients and clinical and laboratory variables were collected. Patients were randomly divided into derivation and validation cohorts. A prediction rule was developed using data from the derivation cohort and tested in the validation cohort. KEY RESULTS: The JAKPOT prediction rule included three variables: (i) red blood cell count >6.45×1012/L, (ii) platelets >350×109/L, and (iii) neutrophils >6.2×109/L; absence of all criteria was effective at ruling out JAK2-positivity with sensitivities 94.7% and 100%, and negative predictive values of 98.8% and 100% in the derivation and validation cohorts, respectively, with an overall low false negative rate of 0.4%. The rule was validated for three different methods of JAK2 testing. Applying this rule to our entire cohort would have resulted in over 50% fewer tests. CONCLUSION: In patients with elevated hemoglobin, the use of a simple prediction rule helps to accurately identify patients with a low likelihood of having a JAK2 mutation, potentially limiting costly over-investigation in this common referral population.
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Policitemia Vera , Policitemia , Humanos , Estudos Retrospectivos , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Policitemia/genética , Hemoglobinas/genética , Mutação , Janus Quinase 2/genéticaRESUMO
PURPOSE: It is well studied that physical function and social background affect the quality of life (QoL) of cancer patients. However, differences in QoL by age and factors affecting health state utility values (HSUV) of patients with hematological malignancies have not yet been sufficiently investigated. Our aim is to investigate the factors that affect QoL and HSUV in such patients. METHODS: A total of 32 patients with hematological malignancies on outpatient chemotherapy were included. QoL and HSUV were evaluated using the EuroQol-5 Dimension 5-level (EQ-5D-5L). Physical function was assessed using grip strength, knee extension strength, 6-min walking distance, and Short Physical Performance Battery (SPPB). Fatigue was assessed using Brief Fatigue Inventory (BFI), and nutritional status was assessed using Mini Nutritional Assessment-Short Form (MNA-SF). RESULTS: In the EQ-5D-5L, a high percentage of the patients were aware of mobility problems and pain/discomfort, and mobility problems were more common in the older-aged group (≥ 65 years old, n = 16) than in the middle-aged group (< 65 years old, n = 16). In addition, the older-aged group showed lower HSUV and physical function. SPPB (ß = 0.38, p < 0.01), BFI (ß = - 0.58, p < 0.01), and MNA-SF (ß = 0.29, p = 0.02) were independent factors affecting HSUV (adjusted R2 = 0.65, p < 0.01). BFI was correlated with HSUV in both older and middle-aged groups. CONCLUSION: Comprehensive supports, to improve lower extremity function, fatigue, and nutritional status, are required to augment QoL and HSUV in patients with hematological malignancies.
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Neoplasias Hematológicas , Qualidade de Vida , Idoso , Fadiga/etiologia , Humanos , Pessoa de Meia-Idade , Dor , Inquéritos e QuestionáriosRESUMO
Next-generation sequencing (NGS) increasingly influences diagnosis, prognosis and management of myelodysplastic syndrome (MDS). In addition to marrow morphology and flow cytometry, our institution performs cytogenetics (CG) and NGS-based testing routinely in patients with suspected MDS. We evaluated the relative value of NGS in the assessment of patients with suspected MDS. We initially compared the diagnostic and prognostic information derived from CG and NGS in 134 patients. NGS enhanced the diagnostic yield compared to CG for clonal myeloid disorders (sensitivity 77% vs. 42·2%; specificity 90·2% vs. 78%; positive predictive value 92·8% vs. 76%; and negative predictive value 70·8% vs. 45·5%). The identification of poor prognosis mutations by NGS altered risk category in 27/39 (69·2%) patients with MDS with good/intermediate risk CG. Subsequently, we prospectively evaluated 70 patients with suspected MDS using an 'NGS-first approach' with CG restricted to samples with morphological abnormalities. We rarely identified mutations or CG abnormalities in patients without dysplastic features. NGS has a superior diagnostic performance compared to CG in patients with suspected MDS. We estimate that by using an 'NGS-first approach' we could reduce karyotyping by approximately 30%.
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Análise Citogenética , Sequenciamento de Nucleotídeos em Larga Escala , Síndromes Mielodisplásicas/genética , Aberrações Cromossômicas , Humanos , Mutação , Síndromes Mielodisplásicas/diagnóstico , Prognóstico , Estudos RetrospectivosRESUMO
The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.
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Bases de Dados Factuais , Lenalidomida/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de SobrevidaRESUMO
The combinations of melphalan, bortezomib, and prednisolone (VMP) and of lenalidomide and dexamethasone (Rd) are standard treatment strategies for transplant-ineligible newly diagnosed multiple myeloma (NDMM). To make the most of these two strategies, we investigated the efficacy and feasibility of first-line treatment with 4 cycles of VMP followed by continuous Rd therapy in a multi-institutional phase 2 study in Japanese patients with transplant-ineligible NDMM. Thirty-six patients of median age 74 years old with NDMM initially received 35-day cycles of VMP: oral melphalan (6 mg/m2) and prednisolone (60 mg/m2) on days 1 to 4 and bortezomib (1.3 mg/m2) on days 1, 8, 15, and 22. After 4 cycles of VMP, treatment was switched to 28-day cycles of Rd, which was continued until disease progression or emergence of an unacceptable adverse event (AE) in 33 patients, while one patient who achieved CR after VMP continued VMP at the physician's discretion. The overall response rates after VMP and after Rd were 66.7% and 86.1%, including CR rates of 5.6% and 36.1%, respectively. In a median follow-up period of 34.3 months, the progression-free survival and overall survival rates at 3 years were 43.2% and 81.3%, respectively. Grade 3-4 hematological AEs included neutropenia (39% with VMP and 24% with Rd) and thrombocytopenia (11% with VMP and 3% with Rd). There was no death due to an AE. In conclusion, sequential therapy with VMP followed by Rd is effective and mostly feasible for transplant-ineligible NDMM. The study is registered as UMIN000034815.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Mieloma Múltiplo/diagnóstico , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Taxa de SobrevidaRESUMO
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells. Introduction of miR-375 reduced PDPK1 expression in human myeloma cell lines (HMCLs), indicating that miR-375 is the dominant regulator of PDPK1 expression. In addition, miR-375 introduction also downregulated IGF1R and JAK2 in HMCLs. CpG islands in the MIR375 promoter were pathologically hypermethylated in all 8 HMCLs examined and in most of 58 patient-derived myeloma cells. Treatment with SGI-110, a hypomethylating agent, and/or trichostatin A, a histone deacetylase inhibitor, increased miR-375 expression, but repressed PDPK1, IGF1R and JAK2 in HMCLs. Collectively, these results show the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways.
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Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Repressão Epigenética/genética , MicroRNAs/genética , Mieloma Múltiplo/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Linhagem Celular Tumoral , Ilhas de CpG/genética , Metilação de DNA , Epigênese Genética , Humanos , MicroRNAs/biossíntese , Gamopatia Monoclonal de Significância Indeterminada/genética , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/metabolismo , Plasmócitos/metabolismo , Recidiva , Transdução de Sinais/genética , Sindecana-1/sangueRESUMO
In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (P<0.0001) and in patients with intermediate cytogenetic risk (P<0.0001) accompanied by a high white blood cell count (P=0.0032). DNA-methylation regulatory gene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged ≤70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.
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Metilação de DNA , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Bandeamento Cromossômico , Terapia Combinada , Feminino , Duplicação Gênica , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Sequências de Repetição em Tandem , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genéticaAssuntos
Calreticulina/genética , Hemoglobinúria Paroxística/genética , Proteínas de Membrana/genética , Proteínas Repressoras/genética , Trombocitemia Essencial/genética , Hemoglobinúria Paroxística/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Trombocitemia Essencial/etiologiaRESUMO
Azacitidine (AZA) has been one of the standard treatments for transplantation-ineligible patients with myelodysplastic syndrome (MDS); however, hematological toxicities frequently cause treatment interruption in the early phase of the therapy. The present study conducted a multicenter retrospective study to investigate the prognostic impacts of various factors, including factors included in the Revised International Prognostic Scoring System (IPSS-R) and severe cytopenia in the early phase of AZA monotherapy in 212 patients with MDS. Severe cytopenia was evaluated after the initiation of therapy by absolute neutrophil counts on the 29th day after AZA (ANC29) initiation, and red cell concentrates (RCC) and platelet concentrate (PC) transfusion units required within 28 days from the start of AZA, designated in the present study as RCC28 and PC28, respectively. The survival period was determined from the 29th day of AZA treatment to death from any cause as the conditional survival period after the first cycle of AZA (CS-AZA1). Multivariate analysis demonstrated that severe thrombocytopenia defined by >30 units of PC28 and very poor risk cytogenetics according to IPSS-R were independent prognostic factors for CS-AZA1. The Kyoto Conditional Survival Scoring System was subsequently developed by incorporating severe thrombocytopenia defined by PC28 and very poor risk cytogenetics, which successfully stratified the risks of the patients in CS-AZA1. In conclusion, extreme PC transfusion dependency during the first cycle of AZA and very poor risk cytogenetics are important prognostic factors in AZA monotherapy for MDS.
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The Japanese Society of Hematology performed an observational cross-sectional study to clarify the morbidity, prognosis, and prognostic factors in patients with COVID-19 with hematological diseases (HDs) in Japan. The study included patients with HDs who enrolled in our epidemiological survey and had a COVID-19 diagnosis and a verified outcome of up to 2 months. The primary endpoints were characteristics and short-term prognosis of COVID-19 in patients with HDs. A total of 367 patients from 68 institutes were enrolled over 1 year, and the collected data were analyzed. The median follow-up among survivors was 73 days (range, 1-639 days). The 60-day overall survival (OS) rate was 86.6%. In the multivariate analysis, albumin ≤ 3.3 g/dL and a need for oxygen were independently associated with inferior 60-day OS rates (hazard ratio [HR] 4.026, 95% confidence interval (CI) 1.954-8.294 and HR 14.55, 95% CI 3.378-62.64, respectively), whereas 60-day survival was significantly greater in patients with benign rather than malignant disease (HR 0.095, 95% CI 0.012-0.750). Together, these data suggest that intensive treatment may be necessary for patients with COVID-19 with malignant HDs who have low albumin levels and require oxygen at the time of diagnosis.
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COVID-19 , Doenças Hematológicas , Humanos , Japão/epidemiologia , Estudos Transversais , COVID-19/epidemiologia , Teste para COVID-19 , Prognóstico , Doenças Hematológicas/epidemiologia , Albuminas , Oxigênio , Estudos RetrospectivosRESUMO
We conducted a multi-institutional retrospective study in 100 transplant-ineligible (TI) patients with diffuse large B-cell lymphoma (DLBCL) that relapsed or progressed after first-line R-CHOP (or -like) therapy to develop a robust predictive model for TI relapsed/refractory (r/r) DLBCL, which has a heterogeneous but poor prognosis by currently available treatment modalities other than chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies. The median age at relapse or progression was 76 years. The median progression-free survival (PFS) and overall survival (OS) from the first progression were 11.5 months and 21.9 months, respectively. Multivariate analysis identified low lymphocyte-to-monocyte ratio (LMR), elevated high lactate dehydrogenase, and elevated C-reactive protein at progression as independent predictors of OS. A predictive model based on these three factors, here designated as the Kyoto Prognostic Index for r/r DLBCL (KPI-R), successfully stratified their OS and PFS with statistical significance. In addition, event-free survival less than 24 months for R-CHOP and low LMR were identified as significant predictive factors for non-response in any sequence of salvage therapy. We concluded that LMR is a bonafide predictor of treatment response and prognosis in patients with TI r/r DLBCL, and may be helpful in treatment decision-making.
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Linfócitos , Linfoma Difuso de Grandes Células B , Monócitos , Humanos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Idoso , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso de 80 Anos ou mais , Linfócitos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Recidiva , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Adulto , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
Multiple myeloma reduces cellular and humoral immunity. Optimal prediction of antibody response to anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with MM and related disorders is essential to prevent coronavirus disease 2019 (COVID-19) during the SARS-CoV-2 pandemic. This study analyzed the humoral response to the anti-SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine and its associated factor in 83 patients from June to November 2021 at seven member institutions of the Kyoto Clinical Hematology Study Group. SARS-CoV-2 neutralizing antibody (nAb) was measured from 12 to 210 days. The result revealed that 40 (48.2%) patients with MM and 59 (100%) healthy controls became seropositive after vaccination. Receiver operating characteristic curve analysis identified serum immunoglobulin (Ig) M of > 18 mg/dL at vaccination as the optimal threshold level associated with seropositivity in the whole cohort. Moreover, the multivariate analysis identified serum IgM of > 18 mg/dL as the independent predictor for a favorable response. Serum IgA level was positively associated with vaccine response in a sub-cohort. Our findings indicate a significant association between immunoparesis and impaired humoral response against mRNA vaccination, including that against SARS-CoV-2, and that serum non-M-protein Ig levels can serve as surrogate biomarkers of nAb production ability.
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COVID-19 , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Anticorpos Antivirais , Vacinas contra COVID-19 , Imunoglobulina M , RNA MensageiroRESUMO
Background: This case report describes the successful management of rehabilitation therapy for a hematological malignancy patient who was receiving chemotherapy and had coronavirus disease 2019 (COVID-19). Case: A 76-year-old man receiving chemotherapy for relapsed refractory multiple myeloma (MM) presented to our hospital with fever and dyspnea and was hospitalized with a diagnosis of COVID-19. Physical therapy (20â min/day, 5 days/week) was started on day 6 of hospitalization while the patient was receiving oxygen therapy. Conditioning exercises and movement exercises were performed in an isolation room, and blood counts, fracture susceptibility, and respiratory status were monitored. The patient was severely immunocompromised and required 34 days of isolation due to persistent severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection. Physical function was assessed by manual muscle testing of the lower extremities and by the extent of lower extremity fatigue and dyspnea on exertion, as assessed using the Borg scale. Motor capacity was assessed using the de Morton Mobility Index (DEMMI) score and the Barthel Index (BI). Muscle weakness and severe dyspnea developed 4 days after physical therapy was started. However, physical therapy led to improvements in DEMMI score and BI. The patient was discharged home on day 43 with home medical care. Discussion: Careful management of MM and COVID-19 facilitated safe treatment with physical therapy. The patient's physical function improved with a carefully planned physical therapy program. Moreover, the patient required prolonged isolation due to persistent viral shedding; however, as a result of the treatment, which was coordinated between physicians and nurses, the patient could be discharged home.
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Background and Purpose: Anti-CD20 monoclonal antibodies (MoAbs), rituximab (RIT), and obinutuzumab (OBZ) are the central components of immunochemotherapy for B-cell lymphoma (BCL). However, these agents potentially cause B-cell depletion, resulting in the impairment of antibody (Ab) production. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the optimal prediction of Ab response against anti-SARS-CoV-2 vaccination is critically important in patients with BCL treated by B-cell depletion therapeutics to prevent coronavirus disease 2019 (COVID-19). Patients and Methods: We investigated the effect of using RIT and/or OBZ on the Ab response in 131 patients with various types of BCL who received the second SARS-CoV-2 mRNA vaccine either after, during, or before immunochemotherapy containing B-cell-depleting moiety between June and November 2021 at seven institutes belonging to the Kyoto Clinical Hematology Study Group. The SARS-Cov-2 neutralizing Ab (nAb) was measured from 14 to 207 days after the second vaccination dose using the iFlash3000 automatic analyzer and the iFlash-2019-nCoV Nab kit. Results: Among 86 patients who received the vaccine within 12 months after B-cell depletion therapy, 8 (9.3%) were seropositive. In 30 patients who received the vaccine after 12 months from B-cell depletion therapy, 22 (73%) were seropositive. In 15 patients who were subjected to B-cell depletion therapy after vaccination, 2 (13%) were seropositive. The multivariate analysis indicated that an interval of 12 months between B-cell depletion therapy and the subsequent vaccination was significantly associated with effective Ab production. Receiver operating characteristic curve analysis identified the optimal threshold period after anti-CD20 MoAb treatment, which determines the seropositivity against SARS-CoV-2, to be 342 days. Conclusion: The use of anti-CD20 MoAb within 12 months before vaccination is a critical risk for poor Ab response against anti-SARS-CoV-2 vaccination in patients with BCL.
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The prognostic impact of patient-related factors, including age, nutritional parameters, and inflammation status, in higher-risk myelodysplastic syndromes (HR-MDS) has been largely unexplored. This multicenter retrospective study aimed to establish a real-world practice-based prognostic model for HR-MDS by considering both disease- and patient-related parameters in 233 patients treated with AZA monotherapy at seven institutions. We found that anemia, presence of circulating blasts in peripheral blood, low absolute lymphocyte count, low total cholesterol (T-cho) and albumin serum levels, complex karyotype, and del(7q) or - 7 were poor prognostic factors. Therefore, we developed a new prognostic model called the Kyoto Prognostic Scoring System (KPSS) by incorporating the two variables with the highest C-indexes (complex karyotype and serum T-cho level). The KPSS classified patients into the following three groups: good (0 risk factors), intermediate (1), and poor (2). Median overall survival for these groups was 24.4, 11.3, and 6.9, respectively (p < 0.001). The discriminatory power of the KPSS was higher than that of the traditional International Prognostic Scoring System. In conclusion, we identified several nutritional parameters with prognostic relevance in patients with HR-MDS and generated a prognostic model consisting of complex karyotype and serum T-cho level that enabled excellent risk stratification.
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Azacitidina , Síndromes Mielodisplásicas , Humanos , Azacitidina/uso terapêutico , Prognóstico , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Cariótipo AnormalRESUMO
We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.
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Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genéticaRESUMO
BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common subtype of indolent ocular adnexal lymphomas. Although radiotherapy (RT) is the standard of care for localized POAML, it can occasionally lead to permanent side effects. Other treatment strategies, such as rituximab (R) monotherapy and immunochemotherapy, have been used for POAML treatment, but their long-term benefits and relative merits remain unclear. While watchful waiting (WW) is a potential option for some indolent lymphomas, the benefits of WW for POAML patients are also unclear. METHODS: We here retrospectively analyzed 75 patients who were diagnosed with POAML between 2008 and 2019 in the institutions of the Kyoto Clinical Hematology Study Group. RESULTS: Commonly involved sites were conjunctiva (42.7%), orbit (36.0%), and lacrimal gland (12.0%), and most patients (92.0%) presented with Ann Arbor stage IE disease. The treatment strategy was selected at the physicians' discretion. More patients without subjective symptoms by tumor mass were subjected to WW (29 patients), while more patients with tumor-derived subjective symptoms were treated by tumor-directed therapy (24 received focal RT, and 19 received R monotherapy). Complete response rates were 79.2% and 42.1% in the RT and R groups, respectively. At 60 months of follow-up, the estimated proportions of POAML patients not requiring new treatment were 69.4%, 85.2%, and 53.8% in the WW, RT, and R groups, respectively. There were no significant differences in the time to start a new treatment between WW and RT groups (median: both not reached [NR], p = 0.187) and between WW and R groups (median: NR vs. 69.0 months, p = 0.554). No specific predictive factor for the future need of treatment was identified in the WW group. CONCLUSION: Our results demonstrate WW may be an acceptable treatment option for POAML, especially for asymptomatic patients.