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Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.
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Linfoma de Células del Manto , Mutación , Humanos , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Estudios Retrospectivos , Anciano , Adulto , Pronóstico , Tasa de Supervivencia , Anciano de 80 o más AñosRESUMEN
In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/mortalidad , Linfoma de Células T Periférico/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Aminopiridinas/uso terapéutico , Benzamidas/uso terapéutico , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , China/epidemiología , Trasplante Autólogo , Anciano , Tasa de Supervivencia , Adulto Joven , Quimioterapia de Mantención , Autoinjertos , Inducción de Remisión , AdolescenteRESUMEN
Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma with a generally aggressive and heterogeneous clinical course. Chemokines are one of the complex components in the tumor microenvironment (TME), and they play a vital role in tumor progression and metastasis. There is no information about the monokine induced by gamma interferon (MIG)/CXC chemokine receptor 3 (CXCR3) axis in patients with MCL. In the present study, we discovered that CXCR3 was highly expressed in MCL tissues and some cell lines including Maver, Z138, and Jeko-1, and significantly associated with clinical factors reflecting high tumor burden in MCL patients. Moreover, elevated serum MIG at diagnosis showed a close relationship with advanced disease and poor prognosis in MCL patients. Additionally, the role of CXCR3 in promoting the proliferation and inhibiting the apoptosis of primary MCL cells and Jeko-1 cells was validated by in vitro experiments. Further research indicated that the MIG/CXCR3 axis mediated MCL cell migration to the TME through the PI3K/AKT signaling pathway. Therefore, the MIG/CXCR3 axis might be a potential target with fewer off-target side effects than other targets in MCL.
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Biomarcadores de Tumor/metabolismo , Quimiocina CXCL9/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfoma de Células del Manto/patología , Receptores CXCR3/metabolismo , Apoptosis , Estudios de Casos y Controles , Proliferación Celular , Femenino , Humanos , Linfoma de Células del Manto/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
BACKGROUND The digestive tract is the most common site of extranodal involvement in diffuse large B cell lymphoma (DLBCL) and its prognostic evaluation is different from that of ordinary DLBCL. Currently, for gastrointestinal lymphoma, in addition to the Ann Arbor staging system, the Lugano and the TNM staging systems are commonly used. However, there is no effective prognostic model to identify poor prognosis in patients with localized gastrointestinal diffuse large B cell lymphoma (GI-DLBCL). MATERIAL AND METHODS This study included 82 patients with GI-DLBCL that had a median follow-up of 75 months, and developed a model (HLAMA) with 5 variables: hemoglobin, age, lactate dehydrogenase (LDH), serum albumin, and the maximum intra-abdominal lesion diameter (MIALD). The specific indicators are: HGB <105 g/L (2 points); LDH ≥300 U/L; age ≥75 years, ALB <38 g/L, MIALD ≥4 cm (each scoring 1 point). We also developed a simplified model, which includes only 3 variables (HGB, LDH, and age). RESULTS HLAMA model and the simplified model both demonstrated good ability to predict prognosis of patients with GI-DLBCL (P<0.001), performing better than the IPI score as it could distinguish low-risk groups in relatively elderly patients (60-75 years old). CONCLUSIONS This study established a prognostic model for diffuse large B cell lymphoma of the gastrointestinal tract. Both the HLAMA model and its simplified version are similar to the IPI score, but could be considered better as they can provide a simpler and more accurate prognostic assessment in patients with GI-DLBCL. For patients with localized GI-DLBCL, our model could distinguish high-risk patients.
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Neoplasias Gastrointestinales/patología , Linfoma de Células B Grandes Difuso/patología , Modelos Estadísticos , Estadificación de Neoplasias/normas , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/terapia , Humanos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To analyze the characteristics of hospital infection of hematological disease, so as to provide reference for clinical therapy. METHODS: Bacterial strains and antimicrobial resistance of patients with hospital infection in Department of Hematology, Peking University Third Hospital from Jan. 2011 to Dec. 2013 were identified and analyzed retrospectively. The specimens were from their blood, urine, sputum, throat swabs and etc. RESULTS: Among the total of 168 isolates of bacteria,the majority of the bacteria strains were from sputum (42.9%); 114 (67.9%) bacteria strains were gram negative and 54 (32.1%) bacteria strains were gram positive; the pathogen testing showed that 20.8% were Pseudomonas aeruginosa,18.5% Escherichia coli,17.9% Staphylococcus aureus, 9.5% Klebsiellar pneumonia, 5.9% Staphylococcus epidermis and 27.4% other bacteria; The gram negative bacilli to cefepime, amikacin and carbapenems showed the lowest antimicrobial resistance rates, and S. aureus showed the lowest antimicrobial resistance rates to vancomycin and linezolid. CONCLUSION: Patients with hemopathy are the main population of hospital infections, the gram negative bacteria are the most common pathogens.It is very important to promptly know the change in distribution of the pathogens in order to rationally select antibiotics and reduce the incidence of bacterial infections.
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Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Antibacterianos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Hematología , Departamentos de Hospitales , Hospitales Universitarios , Humanos , Incidencia , Pruebas de Sensibilidad Microbiana , Estudios RetrospectivosRESUMEN
OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL). METHODS: Clinical data of 113 T lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients from January 2006 to January 2019 were collected from three hematology research centers, including Peking University Third Hospital, the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Medical University. The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients. RESULTS: In 113 T-ALL/LBL patients, 13 cases (11.5%) were diagnosed as ETP-ALL/LBL, including 11 males, with a median age of 28(18-53) years. Compared with non-ETP-ALL/LBL patients, there were no significant differences in age, sex, incidence of large mediastinal mass, clinical stage, international prognostic index (IPI) score, white blood cell (WBC) count and lactate dehydrogenase (LDH) level among ETP-ALL/LBL patients. Among 13 ETP-ALL/LBL patients, 9 cases (69.2%) achieved complete remission (CR), and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients. Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation (allo-HSCT), ETP-ALL/LBL group had a worse 5-year overall survival (OS) rate compared with non-ETP-ALL/LBL group (0 vs 7.1%, P =0.008), while in patients with allo-HSCT, there was no significant difference for 5-year OS rate between the two group (37.5% vs 40.2%, P >0.05). Multivariate Cox regression analysis showed that CR after induction therapy, allo-HSCT, and LDH level were independent prognostic factors affecting T-ALL/LBL patients. CONCLUSION: No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients. Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfocitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adulto , Humanos , Masculino , Persona de Mediana Edad , Respuesta Patológica Completa , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Pronóstico , Estudios Retrospectivos , Femenino , Adolescente , Adulto JovenRESUMEN
OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.
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Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/terapia , Adulto , Masculino , Pronóstico , Femenino , Tasa de Supervivencia , Adulto JovenRESUMEN
Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).
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PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
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Antineoplásicos , Arsénico , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Antineoplásicos/efectos adversos , Arsénico/uso terapéutico , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pandemias , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyze the factors affecting the long-term survival of patients with chronic lymphocytic leukemia (CLL). METHODS: The clinical data of 101 newly diagnosed CLL patients from January 2010 to January 2021 were retrospectively analyzed. Rai and Binet staging systems were used for clinical staging, and CLL-IPI was used for risk stratification of the patients. RESULTS: There were 61 males and 40 females, the median age at diagnosis was 64 (28-84) years, the median PFS (progression-free survival) was 77ï¼66-88ï¼ months, the 2-year and 5-year PFS rates were 85% and 64% respectively. The median OS (overall survival) was 108ï¼103-112ï¼ months, the 5-year and 9-year OS rates were 74% and 46% respectively. Univariate analysis showed that high or very high risk of CLL-IPI, TP53 aberrations, del(17p), need for treatment and different treatment methods were the factors affecting OS (P<0.05); high or very high risk of CLL-IPI, TP53 aberrations, del(17p) and complex karyotype were associated with PFS (P<0.05). By X-tile analysis, it was found that the white blood cell count, the absolute neutrophil count, the hemoglobin level, and ß2-microglobulin level were associated with OS (P<0.05); the white blood cell count, the absolute lymphocytes count, the hemoglobin level, the platelet count, and the lactate dehydrogenase level were associated with PFSï¼Pï¼0.05ï¼. CONCLUSION: The high or very high risk of CLL-IPI, TP53 aberrations, del(17p), need for treatment and different treatment methods are the factors affecting the OS of CLL patients, and high or very high risk of CLL-IPI, TP53 aberrations, del(17p) and complex karyotype are the factors affecting the PFS of CLL patients.
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OBJECTIVE: To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myelomaï¼NDMMï¼ and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment. METHODS: The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survivalï¼PFSï¼ was more than 12 months, they were divided into early relapse groupï¼≤12 monthsï¼ and late relapse groupï¼ï¼12 monthsï¼. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenaseï¼LDHï¼ level, Extramedullary disease (EMD), International Staging Systemï¼ISSï¼ stage, Revised International Staging System ï¼R-ISSï¼ stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridizationï¼FISHï¼, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse. RESULTS: 170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groupsï¼P<0.001ï¼. Fifteen patientsï¼56.0ï¼ ï¼in early relapse group obtained ≥VGPR, and 113ï¼77.9%ï¼ patients in late relapse group, the difference was statistically significantï¼P=0.011ï¼. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse. CONCLUSION: The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Pronóstico , Hibridación Fluorescente in Situ , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Factores de RiesgoRESUMEN
Background: The outcome of patients with acute myeloid leukemia (AML) aged ⩾65 years is poor. Effective treatment options are limited for patients with AML who cannot tolerate intensive chemotherapy. Objectives: We aimed to evaluate the efficacy of low-dose decitabine in previously untreated patients with AML aged ⩾65 years who were ineligible for intensive chemotherapy based on a comprehensive geriatric assessment. Design: We performed a prospective, multicenter, open-label, and non-randomized study. Methods: Patients were enrolled at four centers in Beijing between 1 January 2017 and 31 December 2020. They were treated with decitabine at a dose of 6 mg/m2 for 10 days. The treatment was repeated every 28 days for one cycle for a total of six cycles. The primary endpoint of our study was overall survival (OS) at the end of the first year after enrolment. The secondary endpoints included overall response rate, leukemia-free survival, relapse rate, treatment-related mortality (TRM), quality of life, safety, and transfusion dependence. Patients were continuously monitored for toxicity. Results: Overall, 47 patients (30 males and 17 females) participated in this study. The median age of the enrolled patients was 78 (range, 65-90) years. The median follow-up time was 22.2 (range, 4.6-38.8) months. Fifteen (31.9%) patients achieved complete remission (CR), 11 (23.4%) patients achieved partial remission, 3 (6.4%) patients achieved hematological improvement only, and 18 (38.3%) patients did not achieve remission. The median time to obtain CR was 2 months. The median CR was 8.5 months. Of the patients, 36 (76.6%) patients completed six cycles of treatment with low-dose decitabine, and the 1-year OS was 36.1%. According to instrumental activities of daily living scales, age, comorbidities, and albumin (IACA) scores, the median survival was 11.2 months in the unfit group and 6 months in the frail group. The 1-year OS rates in the unfit and frail groups were 49.2% and 23.4%, respectively. Grade ⩾3 non-hematological toxicity was observed in 70.2% (33/47) of the patients. TRM occurred in three patients. No early deaths occurred after treatment. Conclusion: In newly diagnosed older patients with AML whose IACA assessment was unfit or frail for standard chemotherapy, treatment with low-dose decitabine demonstrated clinical activity and good security in our study.
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BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.
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Linfoma de Células del Manto , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/epidemiología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was 2 (range, 1-4). The median age was 62 years (range, 37-73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. A dose of 150 mg once daily was chosen as the preferred recommended phase 2 dose. After a median follow-up duration of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving a complete response and 53.8% achieving a partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached, and the rate of OS at 24 months was 74.3%. Adverse events (AEs) occurring in >20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥3 AEs were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment because of treatment-related adverse events (TRAEs), but no fatal TRAEs were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179.
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Linfoma de Células del Manto , Neutropenia , Trombocitopenia , Adulto , Humanos , Persona de Mediana Edad , Linfoma de Células del Manto/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Neutropenia/inducido químicamente , Trombocitopenia/inducido químicamenteRESUMEN
OBJECTIVE: To investigate the clinical features and prognostic factors of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of patients with ENKTL from November 2009 to November 2019 was collected and retrospectively analyzed to clarify the clinical features of ENKTL, and evaluate the factors that affected survival and prognosis. RESULTS: Forty-seven patients with ENKTL were collected, median age was 40 (12-82) years old, and more common in males than females, at the ratio of 1.47ⶠ1. The median follow-up was 28 (1-112) months, and 5-year overall survival (OS) rate was 49.3%. The 5-year OS rates of the subjects with ECOG performance stage 0-1 and ≥2 were 51.6% and 0 (P=0.001), respectively. The 5-year OS rates of International Prognostic Index (IPI) score 0-1 and ≥2 were 60.0% and 40.6% (P=0.027), respectively. The 5-year OS rates of Ann Arbor staging â /â ¡ and stage â ¢/â £ were 61.3% and 31.7% (P=0.005), respectively. The 5-year OS rates of the patients with presentation of B symptoms and without presentation of B symptoms were 79.0% and 30.1% (P=0.013), respectively. The 5-year OS rates of plasma EBV-DNA level < 5×102/ml and ≥ 5×102/ml were 60.4% and 33.3% (P=0.003), respectively. The 5-year OS rates of the patients receiving chemotherapy alone, combined chemotherapy and radiotherapy, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) were 12.9%, 86.5%, and 62.5% (P=0.001), respectively. Univariate analysis showed that ECOG score, IPI score, Ann Arbor staging, B symptoms, the copy number of EBV-DNA, and treatment regimens were statistically significant for OS. Multivariate analysis showed that ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens were independent factors of ENKTL OS. CONCLUSION: ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens are independent prognostic factors for OS of patients with ENKTL.
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Linfoma Extranodal de Células NK-T , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma Extranodal de Células NK-T/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
OBJECTIVE: To investigate the clinical characteristics and treatment outcome of patients with Burkitt lymphoma. METHODS: The clinical data of 27 patients with Burkitt Lymphoma were collected and retrospectively analyzed, the clinical characteristics, laboratory data, survival and the factors affecting the prognosis were also analyzed. RESULTS: Among the 27 patients (mainly for adults), the median age was 30 (15-83) years old, the ratio of male and female was 3.5â¶1. There was no EB virus infection in all the patients, 92.6% of the patients showed extranodal organs involvement, 40.7% of them were leukemic stage, 85.2% patients belonged to â ¢ and â £ stage, 74.1% patients belonged to high/high-middle risk according to IPI index. In the terms of molecular biology, five patients were treated with next-generation sequencing test, and the MYC gene mutations were detected out in alt the patients, and the most common mutations were CCND3, ID3 and TP53. The overall response rate (ORR) for all the patients was 85.2%, the complete response (CR) rate was 63.0%, and the partial response rate was 22.2%, the 5-year progression-free survival rate and overall survival rate of the patients was 76.6% and 76.6%, respectively, which showed that the efficacy of the patients in high-dose methotrexate treatment group was higher than that in the non-high high-dose methotrexate treatment group. For the patients treated with LMB89 chemotherapy, the CR was 78.6%, ORR was 100%, the 5-year survival rate was 92.9%, which was superior to the patients treated with other regimens. Auto-hematopoietic stem cell transplantation as consolidation treatment could improve the prognosis for those patients who could not tolerate high-dose chemotherapy. Univariate analysis showed that ECOG score, the level of LDH>500 U/L, WBC level, CNS involvement, short-term effect and LMB89 regimen were the risk factors affecting the prognosis of the patients. CONCLUSION: The adult Burkitt lymphoma are highly aggressive. For the patients in high-dose methotrexate treatment group, especially LMB89 regimen can improve the survival of the patients, and to choose HSCT as a consolidation treatment can be a choice for those patients who could not tolerate high-dose chemotherapy.
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Linfoma de Burkitt , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response. METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort. RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage. CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.
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5-Metilcitosina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Ácidos Nucleicos Libres de Células/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , 5-Metilcitosina/sangre , 5-Metilcitosina/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores Farmacológicos/metabolismo , Estudios de Cohortes , Ciclofosfamida/metabolismo , Ciclofosfamida/uso terapéutico , Desmetilación del ADN/efectos de los fármacos , Doxorrubicina/metabolismo , Doxorrubicina/uso terapéutico , Femenino , Humanos , Modelos Logísticos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prednisona/metabolismo , Prednisona/uso terapéutico , Rituximab/metabolismo , Rituximab/uso terapéutico , Sensibilidad y Especificidad , Vincristina/metabolismo , Vincristina/uso terapéuticoRESUMEN
In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.
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Macroglobulinemia de Waldenström , Anciano , Humanos , Pronóstico , Estudios Retrospectivos , Rituximab , Resultado del Tratamiento , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/epidemiologíaRESUMEN
OBJECTIVE: To investigate the effect of sphingosine-1-phosphate receptor 2 (S1PR2) specific antagonist JTE-013 on the proliferation of human chronic myeloid leukemia (CML) cell line K562. METHODS: K562 cells were treated with JTE-013 (0, 0.5, 1, 5, 10, 20 µmol/L) for 24 and 48 hours respectively, CCK8 assay was used to detect the cell viability. K562 cells were treated with JTE-013 (0, 5, 10, 20 µmol/L) for 24 hours, propidium iodide (PI) DNA staining was used to analyze the cell cycle, Western blot was used to determine the levels of P21 and Cyclin D1 protein expression. RESULTS: JTE-013 inhibited the proliferation of CML cell line K562 in a dose dependent manner (r=-0.971). The proliferation rate of CML cells showed that the activity of CML cells decreased gradually with the increase of JTE-013 concentration (r=-0.971). The detection demonstrated that JTE-013 suppressed tumor cell proliferation through cell cycle arrest in G0/G1 phase. Further detection of the protein expressions of G1 phase regulators showed that level of P21 increased, and expression of Cyclin D1 decreased. CONCLUSION: JTE-013, a S1PR2 antagonist, can inhibit the proliferation of human CML K562 cells, which may be achieved by arresting the cells in G0/G1 phase.