RESUMO
Although MYC and BCL2 co-expression in diffuse large B cell lymphoma (DLBCL) is associated with inferior prognosis, it remains uncertain whether upfront autologous hematopoietic stem cell transplantation (ASCT) is beneficial in this lymphoma. This study aimed to investigate whether ASCT consolidation could have a positive role for patients with MYC and BCL2 co-expression (double-expressor lymphoma, DEL). We retrospectively evaluated 67 DLBCL patients who underwent upfront ASCT following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) were 82.3% and 79.2%, respectively. There were 23 (34.3%) patients with DEL and 51 (76.1%) patients with non-germinal center B cell (GCB) subtype. The 5-year OS and PFS of patients with DEL were not different from those with non-DEL (P = 0.429 and P = 0.614, respectively). No survival difference for OS and PFS was also observed between GCB and non-GCB subtypes (P = 0.950 and P = 0.901, respectively). The OS and PFS were comparable for patients with DEL and non-DEL and both GCB and non-GCB subtypes. In conclusion, MYC and BCL2 co-expression did not have a poor prognostic impact among high-risk patients with DLBCL treated with upfront ASCT regardless of molecular classification. This preliminary study suggested that the role of consolidative ASCT is needed to be evaluated in a prospective randomized clinical trial.
Assuntos
Regulação Neoplásica da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo/métodos , Vincristina/uso terapêutico , Adulto JovemRESUMO
We conducted a retrospective study to evaluate the clinical impact of an early recovery of posttransplant absolute lymphocyte count (ALC) on the outcome of frontline autologous stem cell transplantation (ASCT) for diffuse large B-cell lymphoma (DLBCL). We reviewed 65 DLBCL patients who underwent frontline ASCT after primary chemotherapy based on cyclophosphamide, doxorubicin, vincristine, and prednisone. A receiver operating characteristic analysis was performed to determine the optimal cut point (0.4 × 109 /L) for an ALC at 15 days after ASCT (ALC-15). Both event-free survival and overall survival rates of the higher-ALC-15 group were significantly better than those of the lower-ALC-15 group (event-free survival, P = .008; overall survival, P = .013). The infused CD34+ cell count was significantly associated with the recovery of ALC-15 (>0.4 × 109 /L) after ASCT (P = .028). A multivariate analysis confirmed that a higher infused CD34+ cell dose (>5.0 × 106 cells/kg) was an independent factor affecting an early recovery of ALC after ASCT (odds ratio, 4.145; 95% confidence interval, 1.106-15.528; P = .035). In conclusion, an early recovery of ALC after ASCT can be regarded as a good prognostic marker in patients with DLBCL who have undergone frontline ASCT. We found that the infused CD34+ cell dose for ASCT was associated with the recovery of ALC.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Contagem de Linfócitos/métodos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.
Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Fatores de Transcrição Forkhead/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma/metabolismo , Linfoma/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante AutólogoRESUMO
Upfront autologous stem cell transplantation (ASCT) has shown favourable outcome in patients with primary central nervous system lymphoma (PCNSL), but the role of risk-adapted upfront ASCT consolidation has not been evaluated in PCNSL. As PCNSL patients with the International Extranodal Lymphoma Study Group (IELSG) prognostic score ≥2 or those who did not achieve complete response after two courses of induction chemotherapy (non-CR1) have shown inferior outcomes, we retrospectively analysed the role of upfront ASCT in 66 high-risk (IELSG ≥2 and/or non-CR1) younger (age <65 years) immunocompetent PCNSL patients who achieved at least partial response after initial high-dose methotrexate-based chemotherapy. Nineteen patients who received upfront ASCT exhibited significantly better overall survival (OS, P = 0·021) and progression-free survival (PFS, P = 0·005) compared to 47 patients who did not. In univariate and multivariate analyses, upfront ASCT was associated with better OS (P = 0·037 and P = 0·025, respectively) and PFS (P = 0·009 and P = 0·007, respectively). In a propensity score-matched cohort (n = 36), patients who received upfront ASCT also showed better outcome (P = 0·037 for OS, P = 0·001 for PFS). Our results suggest that upfront ASCT consolidation might be especially beneficial for high-risk PCNSL patients.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada/mortalidade , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão/métodos , República da Coreia , Estudos Retrospectivos , Medição de Risco , Transplante Autólogo , Adulto JovemRESUMO
The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.
Assuntos
Infecções Bacterianas/complicações , Bortezomib/administração & dosagem , Linfopenia/terapia , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções Bacterianas/microbiologia , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco , Taxa de Sobrevida , Transplante HomólogoRESUMO
Optimal treatment strategies for primary central nervous system lymphoma (PCNSL) have not been established. In this study, we investigated the treatment outcomes and prognostic factors of high-dose methotrexate, vincristine, and procarbazine (MVP) chemotherapy followed by an interim response-adapted intensification strategy in immunocompetent patients with PCNSL. We evaluated the evidence of infection with Epstein-Barr virus (EBV) in both brain tumor tissue and whole blood. Forty patients were retrospectively reviewed. Ten (25 %) patients who achieved complete response (CR) in the interim analysis did not receive any additional consolidation treatment after completion of planned high-dose MVP chemotherapy. Additional radiotherapy (n = 9) or autologous stem cell transplantation (ASCT) (n = 7) was performed in patients who did not achieve CR in the interim analysis. The median age was 55 years. The overall CR rate was 62.5 % (n = 25), and the objective response rate was 75.0 %. Two-year overall survival (OS) was 59.8 %, and 2-year progression-free survival was 47.1 %. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 47.5 and 32.5 % of patients, respectively. Treatment-related mortality was 15.0 % (n = 6), and four patients developed delayed neurotoxicity. There was no evidence of EBV-encoded RNA expression in brain tumor tissue. Ten (29.4 %) of 34 patients showed detectable EBV-DNA in whole blood. Poor performance status and EBV-DNA positivity in whole blood were significantly associated with inferior OS (p = 0.032, p = 0.023, respectively). We suggest that high-dose MVP chemotherapy followed by an early response-adapted intensification strategy may be effective and minimize the number of patients who receive radiotherapy or ASCT in the early course of treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/terapia , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4 , Linfoma/terapia , Transplante de Células-Tronco , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autoenxertos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/virologia , DNA Viral/metabolismo , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos da radiação , Humanos , Linfoma/metabolismo , Linfoma/mortalidade , Linfoma/patologia , Linfoma/virologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , RNA Viral/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Elevated serum free light chain (FLC) is known to be an adverse prognostic factor for diffuse large B-cell lymphoma (DLBCL). We hypothesized that monoclonal gammopathy (MG; elevated kappa [κ] or lambda [λ] FLC with an abnormal κ/λ ratio or a positive IF [immunofixation]) and polyclonal gammopathy (PG; elevated κ and/or λ FLC with a normal κ/λ ratio and a negative IF) would have different clinical outcome according to the molecular classification of DLBCL. In addition, MG would be a poor prognostic factor in patients with activated B-cell like type of DLBCL. Molecular classification of DLBCL, such as germinal center B-cell (GCB) type and non-GCB type, was performed according to the Hans algorithm. Among 175 newly diagnosed DLBCL patients, 96 (54.9 %) patients had an elevated FLC. MG and PG were observed in 34 and 68 patients, respectively. The 2-year overall survival (OS) and event-free survival (EFS) rates were 79.0 % and 71.6 %, respectively. In multivariate analysis, high-intermediate/high International Prognostic Index score and elevated FLC were significant for the OS (P = 0.002, P = 0.005, respectively) and EFS (P < 0.002, P = 0.010, respectively). MG and PG were also associated with inferior OS (P = 0.002, P = 0.011, respectively) and EFS (P = 0.002, P = 0.013, respectively). Ninety-six patients from a total 133 evaluable patients were classified to the non-GCB type. Patients with PG showed inferior clinical outcome for OS and EFS in patients with the GCB type (P = 0.006, P = 0.035, respectively). MG was a significant poor prognostic factor for OS and EFS in patients with the non-GCB type (P = 0.017, P = 0.004, respectively). MG was a poor prognostic maker in patients with the non-GCB type and PG was a poor prognostic indicator for the GCB type of DLBCL who were treated with R-CHOP.
Assuntos
Biomarcadores Tumorais/sangue , Cadeias Leves de Imunoglobulina/sangue , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Paraproteinemias/sangue , Paraproteinemias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/classificação , Feminino , Humanos , Cadeias Leves de Imunoglobulina/classificação , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Paraproteinemias/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
Women's empowerment and health literacy are essential for fostering community well-being. Empowering women through education and diverse training plays a crucial role in ensuring their prosperity and overall health. This study investigates the satisfaction and experiences of underprivileged rural mothers participating in a functional literacy education program in the Kailali district, Nepal. We assess participants' perceptions of program effectiveness, examining training content, facilities, and trainers while exploring menstrual hygiene practices and maternal health awareness. Through convenience sampling, 141 underprivileged women from five rural villages near Tikapur were selected from literacy centers run by Mahima Group. Utilizing structured questionnaires and statistical analyses, including descriptive analyses, Spearman's rho correlation, and Pearson's chi-square test, we found that 65.2% of participants expressed high satisfaction levels. Moreover, 96.5% found the program highly effective, with 97.9% reporting improved literacy skills and 96.5% demonstrating increased awareness of menstrual hygiene practices. Additionally, 97.2% agreed that the program enhanced maternal and child health knowledge. Significant correlations were observed among the training course, facilities, trainers, and overall training perception. In line with this, significant associations were found between age groups (p = 0.003) and geographical areas (p = 0.023) with satisfaction levels with the literacy program. These results underscore the satisfaction of participants within the literacy program and its impact on their lives, and advocates for its broader implementation to empower marginalized communities for sustainable development.
RESUMO
Under the global landscape of the prolonged COVID-19 pandemic, the number of individuals who need to be tested for COVID-19 through screening centers is increasing. However, the risk of viral infection during the screening process remains significant. To limit cross-infection in screening centers, a non-contact mobile screening center (NCMSC) that uses negative pressure booths to improve ventilation and enable safe, fast, and convenient COVID-19 testing is developed. This study investigates aerosol transmission and ventilation control for eliminating cross-infection and for rapid virus removal from the indoor space using numerical analysis and experimental measurements. Computational fluid dynamics (CFD) simulations were used to evaluate the ventilation rate, pressure differential between spaces, and virus particle removal efficiency in NCMSC. We also characterized the airflow dynamics of NCMSC that is currently being piloted using particle image velocimetry (PIV). Moreover, design optimization was performed based on the air change rates and the ratio of supply air (SA) to exhaust air (EA). Three ventilation strategies for preventing viral transmission were tested. Based on the results of this study, standards for the installation and operation of a screening center for infectious diseases are proposed.
RESUMO
This study aims to discover whether or not the capacity-building intervention through implementing the "Rural Area Development Program" in Tuyen Quang province, in partnership with the Korea International Cooperation Agency (KOICA) and the Vietnamese Department of Health", would positively affect the perception of the public toward the communal health stations (CHSs). To address this, three specific indicator-related satisfaction levels were examined regarding the infrastructure, the professional skills, and the service attitude of the medical personnel of the three CHSs toward outpatients. This cross-sectional study was conducted with 100 participants from three rural CHSs (Binh Yen, Vinh Loi, and Thang Long Communes). As a researcher-directed survey, a structured questionnaire was adopted to gauge the outpatient satisfaction levels in relation to the three indicators from the CHS medical milieu toward the patients and the medical services received. Descriptive and inferential analyses were performed to determine the perceptions of outpatient satisfaction relating to the three indicators. A higher satisfaction rate was found (overall 89-100% descriptive data with three indicators, as well as significant satisfaction differences in inferential data based on F-ratio and p-value) between the three regions with the three indicators, and two major data showed that the commune with a higher or more significant satisfaction rate or difference was Binh Yan > Vinh Loi > Thang Long. Collectively, this study clearly indicates the positive impact of CHSs capacity-building by implementing the Development Program in Tuyen Quang province with KOICA in relation to the public perception toward CHSs through significantly increased satisfaction levels-specifically, the infrastructure, the professional skills, and the service attitude of the medical milieu from the three CHSs toward outpatients.
Assuntos
Fortalecimento Institucional , Opinião Pública , Humanos , Vietnã , Estudos Transversais , Cooperação InternacionalRESUMO
BACKGROUND/AIMS: Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database. METHODS: This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]). RESULTS: The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS. CONCLUSION: Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Idoso , Dasatinibe , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Adesão à Medicação , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
BACKGROUND/AIMS: Although the use of surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is discouraged in patients with diffuse large B-cell lymphoma, its usefulness in different subtypes has not been thoroughly investigated. METHODS: We retrospectively evaluated 157 patients who showed positive results on surveillance FDG-PET/CT every 6 months following complete response for up to 5 years. All of the patients also underwent biopsies. RESULTS: Seventy-eight (49.6%) of 157 patients had true positive results; the remaining 79 (50.3%), including eight (5.1%) with secondary malignancies, were confirmed to yield false positive results. Among the 78 patients with true positive results, the disease in seven (8.9%) had transformed to a different subtype. The positive predictive value (PPV) of FDG-PET/CT for aggressive B-cell non-Hodgkin's lymphoma (NHL) was lower than that for indolent B-cell or aggressive T-cell NHL (p = 0.003 and p = 0.018, respectively), especially in patients with a low/low-intermediate international prognostic index (IPI) upon a positive PET/CT finding. On the other hand, indolent B-cell and aggressive T-cell NHL patients showed PPVs of > 60%, including those with low/low-intermediate secondary IPIs. CONCLUSION: The role of FDG-PET/CT surveillance is limited, and differs according to the lymphoma subtype. FDG-PET/CT may be useful in detecting early relapse in patients with aggressive T-cell NHL, including those with low/low-intermediate risk secondary IPI; as already known, FDG-PET/CT has no role in aggressive B-cell NHL. Repeat biopsy should be performed to discriminate relapse or transformation from false positive findings in patients with positive surveillance FDG-PET/CT results.
Assuntos
Linfoma não Hodgkin , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
PURPOSE: Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study, the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. MATERIALS AND METHODS: We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 µM AG-221 and 100 nM ATRA, alone or in combination. RESULTS: Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment. CONCLUSION: Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.
Assuntos
Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Tretinoína/farmacologia , Triazinas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Isocitrato Desidrogenase/antagonistas & inibidores , Isocitrato Desidrogenase/metabolismo , Leucemia Mieloide Aguda/genética , MutaçãoRESUMO
PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML. MATERIALS AND METHODS: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively. RESULTS: The median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1-14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine. CONCLUSION: Five-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/uso terapêutico , Metilação de DNA , Decitabina , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , República da Coreia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Because there are few studies regarding the clinical impact of circulating EBV-DNA in peripheral T-cell lymphomas (PTCLs), we tried to evaluate the role of EBV-DNA in whole blood as a prognostic factor for PTCL. We retrospectively reviewed 110 PTCL patients with median age of 63 (20-94) years. Forty-seven patients (42.7%) showed positive results for EBV-DNA, and these patients also had stage III/IV disease, elevated lactic dehydrogenase, and low albumin level (P = 0.007, P = 0.004, P = 0.002, respectively). The 5-year overall survival (OS) and progression free survival (PFS) were 21.0% and 18.0%. Univariable analysis showed that positive EBV-DNA was related with inferior OS and PFS (P = 0.015 and P < 0.001, respectively). Multivariable analysis showed that poor performance status, extranodal involvement more than one site and positive EBV-DNA results were related with OS and PFS (P < 0.001, P < 0.001, P = 0.007 and P = 0.001, P = 0.002, P < 0.001, respectively). Using these three variables, we made a new prognostic model which classified patients on risk as follows: low, no adverse factors; intermediate, 1 factor; or high, 2-3 factors. The new prognostic model could stratify the three groups for OS and PFS better than either international prognostic index or prognostic index of PTCL-u, and showed statistical significance in PTCL, not otherwise specified. This study suggests that whole blood EBV-DNA is related with aggressive clinical characteristics and inferior survival. The new prognostic model, which incorporates EBV-DNA, could better stratify PTCL patients.
RESUMO
BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass composed of malignant myeloid precursor cells without any evidence of leukemia in the peripheral blood and bone marrow. We describe the clinical characteristics and outcomes of patients diagnosed with isolated MS at our institution. METHODS: We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%) with isolated MS. Isolated MS patients were divided into 2 groups according to the first-line treatment strategy: systemic treatment only (S) or local treatment with or without systemic treatment (LS). RESULTS: The most common site of MS occurrence was the head and neck area (N=4, 44.4%), followed by the anterior mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months (range, 2.4-20.1 mo). The number of patients achieving complete remission after first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various modalities and the early initiation of intensive combined treatment may be the optimal strategies to reduce the risk of isolated MS subsequently evolving to AML. To fully understand the characteristics of isolated MS, a larger number of patients from a multinational study is necessary.
RESUMO
Autophagy is a lysosomal degradation mechanism that is essential for cell survival, differentiation, development, and homeostasis. Autophagy protects cells from various stresses, including protecting normal cells from harmful metabolic conditions, and cancer cells from chemotherapeutics. In the current study, a cytarabine arabinoside (AraC)sensitive U937 leukemia cell line and an AraCresistant U937 (U937/AR) cell line were assessed for baseline autophagy activity by investigating the LC3I conversion to LC3II, performing EGFPLC3 puncta, an acidic autophagolysosome assay, and measuring the expression of various autophagyrelated genes. The results demonstrated significantly higher autophagic activity in the U937/AR cells compared with the U937 cells, when the cells were cultured with or without serum. Furthermore, an increase in the autophagic activity in starved U937/AR cells was demonstrated, compared with that in the starved U937 cells. Administration of an autophagy inhibitor demonstrated no change in cell death in the two cell lines when cultured with serum, however, it induced cell death regardless of the AraC sensitivity when the cell lines were cultured without serum. In addition, the U937 cells demonstrated an AraC resistance when cultured without serum. Cotreatment with AraC and the autophagy inhibitor significantly induced cell death in the U937/AR and AraCsensitive U937 cells. In conclusion, autophagy serves an important role in protecting U937 cells from AraC and in the development of AraC resistance. Inhibition of autophagy combined with the AraC treatment in the U937 cells augmented the antileukemic effect of AraC and overcame AraC resistance, suggesting that autophagy may be an important therapeutic target to further improve the treatment outcome in patients with acute myeloid leukemia.
Assuntos
Autofagia/efeitos dos fármacos , Citarabina/farmacologia , Antimetabólitos Antineoplásicos/farmacologia , Western Blotting , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Genes Reporter , Proteínas de Fluorescência Verde/genética , Humanos , Hidroxicloroquina/toxicidade , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Células U937RESUMO
Few studies have evaluated the risk factors for hepatic sinusoidal obstructive syndrome (SOS) in patients with malignant lymphoma receiving autologous stem cell transplantation (ASCT). We retrospectively analyzed 132 malignant lymphoma patients who underwent ASCT. Intravenous busulfan-based conditioning regimens were used in 108 (81.8%) patients. The combination of heparin and ursodeoxycholic acid was used for prophylaxis of SOS. Hepatic SOS was developed in 10 (7.6%) patients at a median of 30 days post-ASCT. In nine (90.0%) patients, SOS was diagnosed after 20 days post-ASCT. Two patients developed severe SOS and eventually died from multiple organ failure. In multivariate analysis, the use of the busulfan-thiotepa conditioning regimen (p = 0.003) and a high pre-transplant serum ferritin level (≥ 950 ng/mL) (p = 0.003) were risk factors for hepatic SOS. The evaluation of pre-transplant serum ferritin may be helpful in determining the most appropriate conditioning regimen with a lower risk of SOS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ferritinas/sangue , Hepatopatia Veno-Oclusiva/etiologia , Linfoma/sangue , Linfoma/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Humanos , Linfoma/complicações , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Fatores de Risco , Índice de Gravidade de Doença , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Adulto JovemRESUMO
PURPOSE: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma (NHL). Absolute lymphocyte count (ALC) has been suggested to have a prognostic value in several subtypes of NHL. We evaluated the prognostic significance of clinical factors, including ALC, in patients with PCNSL to develop a new prognostic model. METHODS: We analysed prognostic factors, including ALC, at diagnosis in 81 PCNSL patients receiving high-dose methotrexate-based therapy. RESULTS: The median ALC at diagnosis was 1210 × 10(6)/L (range, 210-3610), with lymphopenia (≤ 875 × 10(6)/L) being detected in 27 (33.3%) patients. In the multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) >1 (hazard ratio [HR] 3.18, P=0.003), age >50 years (HR 4.23, P=0.012), and lymphopenia at diagnosis (HR 2.83, P=0.008) remained independent prognostic factors for low overall survival (OS). Lymphopenia was also a significant prognostic factor for progression-free survival (HR 3.17, P=0.001). By means of a new three-factor prognostic model using ECOG PS >1, age >50 years, and presence of lymphopenia, with 1 point assigned to each factor, we successfully classified the patients into three risk groups: low (0 and 1), intermediate (2), and high (3). The 5-year OS rates of the patients in the low-, intermediate-, and high-risk groups were 74.3%, 21.7%, and 12.5%, respectively (P<0.001). CONCLUSIONS: Low ALC is a useful indicator of poor prognosis in patients with PCNSL. The proposed three-factor model should be validated in large-scale studies.