RESUMEN
Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1-2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.
Asunto(s)
Arsénico , Arsenicales , Leucemia Promielocítica Aguda , Humanos , Adulto , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Trióxido de Arsénico/uso terapéutico , Trióxido de Arsénico/efectos adversos , Arsénico/uso terapéutico , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Óxidos/uso terapéutico , Arsenicales/efectos adversosRESUMEN
BACKGROUND: Exosomes derived from tumor cells (TEXs) are involved in both immune suppression, angiogenesis, metastasis and anticancer stimulatory, but the biological characteristics and role of diffuse large B cell lymphoma (DLBCL)-derived exosomes have been less investigated. METHODS: Exosomes (EXOs) were isolated from OCI-LY3, SU-DHL-16, and Raji cells and biological characteristics of EXOs were investigated using electron microscopy, flow cytometry analysis, and Western blot analysis. The protein expression of EXOs was determined by an antibody array. Next, the communication between EXOs and lymphoma cell, stromal cell, dendritic cells (DCs), and T cells was evaluated. Finally, effect of DLBCL TEXs on tumor growth in vivo was investigated. RESULTS: We demonstrated that EXOs derived from DLBCL cell lines displayed malignancy molecules such as c-Myc, Bcl-2, Mcl-1, CD19, and CD20. There was a different protein expression pattern between DLBCL TEXs and Burkitt lymphoma TEXs. DLBCL TEXs were easily captured by DCs and lymphoma cells, and mainly acted as an immunosuppressive mediator, evidenced by induction of apoptosis and upregulation of PD-1 in T cells. Furthermore, the TEXs stimulated not only cell proliferation, migration of stromal cells but also angiogenesis. As a result, the TEXs promoted tumor growth in vivo. On other hand, DLBCL TEXs did not induce apoptosis of DCs. After pulsed with the TEXs, DCs could stimulate clonal expansion of T cells, increase the secretion of IL-6 and TNFα, and decrease the production of immunosuppressive cytokine IL-4 and IL-10. The T cells from tumor bearing mice immunized by TEX were shown to possess superior antilymphoma potency relative to immunization of tumor lysates. CONCLUSIONS: This study provides the framework for novel immunotherapies targeting TEXs in DLBCL.
Asunto(s)
Vacunas contra el Cáncer/inmunología , Células Dendríticas/inmunología , Exosomas/inmunología , Inmunoterapia/métodos , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/terapia , Animales , Vacunas contra el Cáncer/farmacología , Carcinogénesis/inmunología , Comunicación Celular/inmunología , Línea Celular Tumoral , Células Dendríticas/patología , Exosomas/patología , Humanos , Linfoma de Células B Grandes Difuso/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Linfocitos T/inmunología , Linfocitos T/patología , Microambiente Tumoral/inmunologíaRESUMEN
OBJECTIVE: To evaluate the therapeutic efficacy of VICP+L-ASP/TKI on adult patients with B-ALL and to explore the influence factors. METHODS: Forty-one adult B-ALL patients treated with VICP+L-ASP/TKI from August 2008 to June 2014 were following-up. The complete remission(CR) rate, toxicity, overall survival(OS) and event free survival(EFS) after induction treatment were analyzed, the therapeutic outcome of patients between different risk stratification subgroups was compared, the influence of standardized consolidatory and maintaining treatment as well as allogeneic hematopoietic stem cell transplantation(allo-HSCT) on survival time was analyzed. RESULTS: The early death not occurred in 41 patients with B-ALL including 37 cases with CR; the CR rate of 1 course treatment was 90.2%. The follow-up time lasted to March 17, 2015, the median follow-up time was 25(9-79) months; the 1 year OS rate was 75.3%, the EFS rate was 58.3%. Analysis of risk factors showed that the initial WBC count over 30×109/L, LDH over 250 U/L and minimal residual disease(MRD) over 10-4 after treatment were poor prognostic factors. After remission, the standardized consolidatory treatment or allo-HSCT according to the "2012 China adult ALL diagnosis and treatment expert consensus" could improve long-term survival, 3 years OS rate was 73.8% and 61.5% respectively, 3 years EFS were 63.5% and 65.7% respectively. The main toxic and side effects were hematologic reactions, the hematologic adverse reaction of IV grade was observed in 97.6%(40/41) during induction treatment. CONCLUSION: Induction chemotherapy based on VICP+L-ASP/TKI and standardized consolidatory after remission according to the "2012 China adult acute lymphoblastic leukemia diagnosis and treatment expert consensus" can improve the therapeutic efficacy. The allo-HSCT should be actively performed for B-ALL paients with high risk(elevated initial WBC count and LDH level); at some time, the regularly monitoring MRD and adjusting therapeutic protocol according to monitoring result can promote the prognosis of adult B-ALL patients.
Asunto(s)
Quimioterapia de Inducción , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , China , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas , Humanos , Recuento de Leucocitos , Neoplasia Residual , Pronóstico , Inducción de Remisión , Factores de RiesgoRESUMEN
Decitabine (DAC) is commonly used for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Previous studies have indicated DAC sequentially combined with idarubicin was an effective treatment for myeloid neoplasms. Therefore, a clinical study was conducted of the sequential combination of DAC followed by low-dose idarubicin/cytarabine in high-risk myeloid neoplasms. A total of 30 patients with a diagnosis of high-risk MDS, AML evolving from MDS or relapsed/refractory AML were enrolled in the study. DAC was administered 20 mg/m(2) daily for 3 consecutive days. Idarubicin (3 mg/m(2)/day) was administered 24 h after the last administration of DAC for 5-7 consecutive days, combined with cytarabine (30 mg/m(2)/day) for 7-14 days. The overall complete remission rate was 66.67%. The results demonstrate that epigenetic priming with decitabine followed by low-dose idarubicin/ytarabine has an increased anti-leukemia effect compared to traditional chemotherapy in high-risk myeloid neoplasms.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azacitidina/análogos & derivados , Epigénesis Genética/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azacitidina/administración & dosificación , Azacitidina/uso terapéutico , Aberraciones Cromosómicas , Citarabina/administración & dosificación , Decitabina , Progresión de la Enfermedad , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide Aguda/diagnóstico , Masculino , Persona de Mediana Edad , Mutación , Síndromes Mielodisplásicos/diagnóstico , Recurrencia , Inducción de Remisión , Resultado del TratamientoRESUMEN
The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , China , Femenino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Nucleofosmina , Pronóstico , Factores de Tiempo , Adulto JovenAsunto(s)
Linfocitos B Reguladores , Terapia de Inmunosupresión , Trombocitopenia/sangre , Trombocitopenia/inmunología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trombocitopenia/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To assess the prevalence and clinical characteristics of isocitrate dehydrogenase 1 and 2 (IDH 1 and IDH2) gene mutations in myelodysplastic syndrome (MDS) patients. METHODS: Pretreatment bone marrow specimens were enriched for mononuclear cells in 108 adult patients with de novo MDS from January 2006 to August 2012. Genomic DNA was extracted from mononuclear cells. And PCR and direct sequencing were performed to sequence exon 4 of IDH gene. RESULTS: IDH mutations were discovered in 11 MDS patients (10.19%, 11/108) and all were heterozygous. The frequencies of IDH1 and IDH2 mutations were 5.56% (6/108) and 4.63% (5/108) respectively. Only one type of IDH1 mutation (c.394Câ, p.R132C) was identified in our cohort. All IDH2 mutations caused the changes of R140 (c.419GâA, p.R140Q). However IDH2 R172 mutation was not detected. The combined mutations of IDH1 and IDH2 were not simultaneously observed in the same patient. The prevalence of IDH mutation was higher in advanced-stage MDS than those early-stage MDS patients. Mutated and wild-type groups had significantly difference in bone marrow blast percentage (median 12.5% vs 6.0%, P = 0.013) at diagnosis, but not in white blood cell count, hemoglobin level and platelet count, etc. In the normal karyotype group, the frequencies of IDH mutations were as similar as those in the abnormal karyotype group (10.61% (7/66) vs 10.00% (4/40), P > 0.05). The median follow-up time was 472 d, our data indicated that IDH mutations were correlated with poor overall survival (median time 512 vs 740 d, P = 0.017). IDH mutations were also an inferiorly predictive factor in the intermediate-1 group patients of International Prognostic Scoring System (IPSS) (median survival time 512 d vs not reached, P = 0.038). There was also better efficacies than other treatments in IDH mutation positive patients (median survival time 623 vs 165 d, P = 0.049). CONCLUSIONS: IDH mutation is a vital biomarker for better risk stratification of MDS patients with and improving IPSS. Hypomethylation agents may be effective for treating IDH mutation positive patients.
Asunto(s)
Isocitrato Deshidrogenasa/genética , Mutación , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Exones , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Pronóstico , Adulto JovenAsunto(s)
Antifúngicos/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Micosis/tratamiento farmacológico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Hematológicas/microbiología , Humanos , Masculino , Persona de Mediana Edad , Micosis/complicaciones , Resultado del Tratamiento , Voriconazol , Adulto JovenRESUMEN
Patients with hematologic disease are likely to be at increased risk for infection with influenza. We retrospectively analyzed 11 cases of patients with hematologic disease who were infected with pandemic H1N1 virus in our department, including their clinical manifestations, laboratory and imaging findings, outcomes of antiviral therapy, and factors associated with mortality. Notably, nine patients had lower respiratory tract disease. Five patients progressed to respiratory failure and eventually died, despite treatment with antivirals and/or corticosteroids and/or mechanical ventilation. We concluded that H1N1 2009 infection was associated with a severe course and high rate of mortality in patients with hematologic disease, and early diagnosis and antiviral treatment were important to reduce the rate of severe complications and mortality.
Asunto(s)
Enfermedades Hematológicas/complicaciones , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/complicaciones , Corticoesteroides/uso terapéutico , Adulto , Antivirales/uso terapéutico , Femenino , Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/diagnóstico , Gripe Humana/mortalidad , Gripe Humana/terapia , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a fine needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib.