RESUMEN
Therapy-related acute myeloid leukemia (t-AML) usually stems from exposure of the bone marrow to cytotoxic chemotherapy and/or radiation therapy. t-AML is usually associated with poor overall survival, but occasionally t-AML can involve favorable-risk cytogenetics, including core binding factor AML (CBF-AML), which shows a recurrent chromosomal rearrangement with t(8;21) (q22;22) and 'inv(16) (p13.1;q22)/t(16;16)(p13.1;q22)', leading to 'RUNX1::RUNX1T1 and CBFB::MYH11' fusion genes, respectively. Therapy-related CBF-AML (t-CBF-AML) accounts for 5-15% of CBF-AML cases and tends to have better outcomes than t-AML with unfavorable cytogenetics. Although CBF-AML is sensitive to high-dose cytarabine, t-CBF-AML has worse overall survival than de novo CBF- AML. The objective of this review is to discuss the available data on the pathogenesis, mutations, and therapeutic options in patients with t-CBF-AML.
Acute myeloid leukemia (AML) is a type of cancer of the white blood cells. AML can rarely arise from prior treatment with radiation and/or chemotherapy and are referred to as therapy-related AML (t-AML). Usually t-AML is associated with poor outcomes; however, rarely you may see favorable outcomes with therapy related core binding factor AML. In this paper, we discuss about t-CBF-AML, which is a favorable subtype of t-AML.
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BACKGROUND/AIM: There is no standard salvage chemotherapy for metastatic periampullary adenocarcinoma and duodenal adenocarcinoma and the prognosis of those who fail oxaliplatin, irinotecan, and 5FU is dismal. We examined nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for these two malignancies. METHODS: Patients who failed oxaliplatin, irinotecan, and 5FU and whose archival tumors stained immunohistochemical (IHC) tumor positive for CK7 or MUC1 received nab-paclitaxel and gemcitabine therapy with or without cisplatin. RESULTS: Three patients, 2 with metastatic ampullary adenocarcinoma and 1 with duodenal adenocarcinoma with positive IHC staining for CK7 or MUC1 who failed 2 lines of chemotherapy with oxaliplatin, irinotecan, and 5FU received nab-paclitaxel and gemcitabine with or without cisplatin. All achieved excellent tumor response on CT scans with marked falls in tumor markers CA19-9 and CEA as well as ≥1 year of progression-free survival. All 3 have continued to survive 2-3 years since diagnosed with stage 4 metastatic adenocarcinoma. CONCLUSIONS: Nab-paclitaxel plus gemcitabine with or without cisplatin should be investigated as a standard-of-care chemotherapy regimen for patients with ampullary adenocarcinoma and duodenal adenocarcinoma.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Ampolla Hepatopancreática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Duodenales/tratamiento farmacológico , Neoplasias Duodenales/patología , Adenocarcinoma/etiología , Albúminas/administración & dosificación , Ampolla Hepatopancreática/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias Duodenales/etiología , Femenino , Humanos , Inmunohistoquímica , Masculino , Metástasis de la Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , GemcitabinaRESUMEN
AIMS: We developed an outcomes model to select patients for renal cell cancer vaccine immunotherapy. MATERIALS AND METHODS: We examined clinical data from 2 phase II studies of modified vaccinia Ankara as vector to express 5T4 (MVA-5T4), calculated progression-free survival (PFS) and overall survival (OS), and created risk groups based on the number of factors involved. RESULTS: Median OS was 12.4 months; median PFS was 3.6 months. Significant factors (p<0.05) included neutrophils (both), bone metastases (OS), ECOG performance status (OS), lactate dehydrogenase levels (both), prior therapy with tyrosine kinase inhibitors plus immunotherapy (OS), Fuhrman grade (OS), and 5T4-specific ELISPOT response (PFS). By group, median OS was not reached in patients with favorable risk (censored at cutoff), was 13.7 months in those with intermediate risk and 4.0 months in those with poor risk. CONCLUSIONS: Further validation of this model will identify the patients most likely to respond to MVA-5T4 and provide a framework for outcomes models for other vaccine therapies.
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Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Anciano , Carcinoma de Células Renales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Factores de Riesgo , Resultado del Tratamiento , Vacunas de ADNRESUMEN
Folate immune (EC90 vaccine with GPI-0100 adjuvant followed by EC17) is a novel folate-targeted hapten immunotherapy designed to exploit the overexpression of folate receptors on renal cell carcinoma (RCC) cells. In this open-label, phase I/II clinical study, we report the safety, pharmacokinetics, and antitumor activity of folate immune with concurrent interleukin-2 (IL-2) and interferon-α (IFN-α) in patients with recurrent or metastatic RCC. Twenty-four patients were enrolled. Following 2 phase I cohorts of 6 patients each, we extended the study to 12 additional patients: 18 received weekly vaccination of 1.2 mg of EC90 with 3.0 mg of GPI-0100 adjuvant for 4 weeks. Beginning on cycle 1, day 8, 0.3 mg/kg of EC17 was administered once daily, 5 days per week (Monday-Friday) for 4 consecutive weeks. Beginning on cycle 1, day 15, IL-2 and IFN-α were administered at doses of 12 and 3.0 MIU, respectively, after the EC17 dose, 3 times per week (Monday, Wednesday, and Friday) for 3 weeks. In cycle 2, IL-2 and IFN-α, doses of 7.0 and 3.0 MIU, respectively, were administered 3 days per week (Monday, Wednesday, and Friday) for 4 consecutive weeks. No dose-limiting toxicities were observed. Most adverse events reported were grade 1 or 2, with only twelve grade ≥3 toxicities reported. Sixteen patients had progressive disease, 7 patients were observed to have stable disease, and 1 patient achieved a partial response lasting 71 days. Overall, folate immune plus low-dose IFN-α and IL-2 was safe and well tolerated with some observed clinical activity.
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Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Ácido Fólico/inmunología , Haptenos/inmunología , Interferón-alfa/uso terapéutico , Interleucina-2/uso terapéutico , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Adulto , Anciano , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Carcinoma de Células Renales/patología , Esquema de Medicación , Femenino , Fluoresceína , Ácido Fólico/administración & dosificación , Ácido Fólico/efectos adversos , Haptenos/administración & dosificación , Haptenos/efectos adversos , Humanos , Inmunoterapia , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Interleucina-2/administración & dosificación , Interleucina-2/efectos adversos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: The mTOR inhibitor, everolimus, is approved for the treatment of metastatic renal cell carcinoma (RCC). However, prognostic models are needed to determine the patients who would most benefit from this therapy. We have developed a model based on clinical parameters and patient stratification into risk groups to predict patients with RCC who will derive the most benefit from treatment with everolimus. METHODS: We assessed retrospective data on 57 patients with RCC who received everolimus after previous treatment with immunotherapy or tyrosine kinase inhibitors to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). In the original phase II study, patients received 10mg of everolimus daily without interruption and were assessed every other week for the first 8 weeks on therapy and every 4 weeks thereafter. Kaplan-Meier analysis was used to calculate OS and PFS. Univariate and multivariate analyses were constructed using the Cox proportional hazards model and a stepwise procedure to validate the data. RESULTS: We grouped patients according to risk: 0 prognostic factors indicated favorable risk, 1 to 2 factors intermediate risk, and≥3 factors poor risk. We found notable differences in median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo for poor risk). Three risk factors (prior radiation treatment, no lung metastasis present at the start of treatment, and lymphocytes<25cells/µl) in the multivariate analysis were found to be associated with PFS, and 4 risk factors were found to be associated with OS (bone metastasis at start of treatment, LDH>1.5×upper limit of normal, alkaline phosphatase>120U/l, and lymphocytes<25cells/µl). CONCLUSIONS: Our prognostic model includes 3 readily available clinical parameters for PFS and 4 readily available clinical parameters for OS to help stratify patients into poor, intermediate, and favorable prognosis groups for the treatment of everolimus in clear cell RCC. These intriguing results warrant further study in a larger patient population to validate the findings.