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1.
BMC Cancer ; 21(1): 993, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488662

RESUMEN

BACKGROUND: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. METHODS: FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. RESULTS: Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. CONCLUSION: The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Dexametasona/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Hidrazinas/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/patología , Pronóstico , Tasa de Supervivencia , Triazoles/administración & dosificación
2.
Am J Hematol ; 94(7): 794-802, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31021005

RESUMEN

Twice-weekly carfilzomib (27 mg/m2 ) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m2 ) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty-six RRMM patients enrolled: 22 during dose evaluation (56-mg/m2 , n = 10; 70-mg/m2 , n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m2 ). After 2 fatal adverse events (AEs) during 70-mg/m2 dose expansion, dosage reduction to 56 mg/m2 was permitted. Results are presented for carfilzomib 56-mg/m2 (n = 10) and 70-mg/m2 groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m2 (56-mg/m2 group) and 62.4 mg/m2 (70-mg/m2 group). Grade ≥3 AE rates were 70.0% (56 mg/m2 ) and 69.6% (70 mg/m2 ). Overall response rates were 90.0% (56 mg/m2 ) and 89.1% (70 mg/m2 ); ≥very good partial response rates were 50.0% (56 mg/m2 ) and 73.9% (70 mg/m2 ). Once-weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Femenino , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Recurrencia
3.
Br J Haematol ; 182(4): 513-520, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29974936

RESUMEN

The management of multiple myeloma (MM) has evolved with the increased use of autologous haematopoietic cell transplantation (AHCT) and the introduction of new agents. AHCT and lenalidomide maintenance have been associated with increased risk of second primary malignancy (SPM). We iseutilised the Surveillance, Epidemiology and End Results 13 registries to analyse 9 833 patients diagnosed at age <65 years for three eras: 1995-99 (pre-thalidomide, limited use of AHCT), 2000-04 (post-thalidomide, pre-lenalidomide and bortezomib, increased isautilisation of AHCT) and 2005-09 (post-lenalidomide and bortezomib, higher isautilisation of AHCT). Changes in risk of SPM were assessed by utilising standardised incidence ratio (SIR) and cause-specific risk of death. Cumulative incidence of SPM at 90 months was 4·7%, 6·0% and 6·3% respectively, P = 0·0008. SIR for haematological malignancies in years 1-5 increased, from 1·28 (95% confidence interval [CI] 0·47-2·78) in 1995-99 to 2·17 (95% CI: 1·27-3·48) in 2005-09, due to increased risk of acute leukaemias and lymphomas. A similar trend was observed in years 6-10. Overall mortality in patients with MM declined sharply over time due to declines in MM-associated and cardiovascular mortality with no increase in risk of death from SPM. The evolution of MM therapy is linked to population-level increase in risk with no discernible effect in death from SPM.


Asunto(s)
Mieloma Múltiple , Neoplasias Primarias Secundarias , Sistema de Registros , Adolescente , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/terapia , Factores de Riesgo , Tasa de Supervivencia
4.
Biol Blood Marrow Transplant ; 23(9): 1473-1477, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28546074

RESUMEN

Light chain amyloidosis (AL) results in tissue deposition of misfolded proteins, causing organ dysfunction. In an era of modern therapies, such as bortezomib, reassessment of the benefit of autologous hematopoietic cell transplantation (AHCT) should be considered. In this study, we compared outcomes between patients with AL receiving chemotherapy alone (CT) and those undergoing AHCT. Seventy-four patients with AL were analyzed retrospectively. Two cohorts of patients were studied, those receiving CT (n = 31) and those undergoing AHCT (n = 43). Of the 43 patients in the AHCT cohort, 29 received induction chemotherapy before AHCT, whereas 14 proceeded straight to AHCT without induction therapy. Compared with the CT cohort, patients in the AHCT cohort were younger and had higher ejection fractions, lower brain natriuretic peptide levels, and more severe proteinuria. The majority (87%) of patients in the CT cohort received bortezomib-based treatment. Transplantation-related mortality (TRM) was 7%. Patients receiving AHCT were more likely to achieve complete or very good partial response (P = .048). The median progression-free survival (PFS) and overall survival (OS) were superior in the AHCT cohort (not reached versus 9 months; P < .01 and 74 months versus 8 months; P = .03, respectively). Multivariable analysis demonstrated that improved PFS (hazard ratio, 3.86; 95% confidence interval [CI] 1.3 to 11.5; P = .02) and OS (hazard ratio, 5.6; 95% CI, 1.9 to 16; P < .001) were associated with use of AHCT compared with CT. Patients in the AHCT cohort had deeper and longer durations of response, with superior PFS and OS, compared with those in the CT cohort. Despite the limitations of this study, AHCT should be considered for eligible patients with AL at experienced transplantation centers that can offer this therapy with a low risk of TRM.


Asunto(s)
Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Proteinuria/terapia , Adulto , Anciano , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/inmunología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Quimioterapia de Inducción/métodos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Péptido Natriurético Encefálico/sangre , Modelos de Riesgos Proporcionales , Proteinuria/inmunología , Proteinuria/mortalidad , Proteinuria/patología , Estudios Retrospectivos , Volumen Sistólico/fisiología , Trasplante Autólogo , Resultado del Tratamiento
6.
Biol Blood Marrow Transplant ; 21(12): 2061-2068, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26327628

RESUMEN

Engraftment syndrome (ES) encompasses a continuum of periengraftment complications after autologous hematopoietic stem cell transplantation. ES may include noninfectious fever, skin rash, diarrhea, hepatic dysfunction, renal dysfunction, transient encephalopathy, and capillary leak features, such as noncardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication.


Asunto(s)
Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/uso terapéutico , Linfoma/terapia , Mieloma Múltiple/terapia , Síndrome POEMS/terapia , Encefalopatías/etiología , Encefalopatías/inmunología , Encefalopatías/patología , Encefalopatías/terapia , Síndrome de Fuga Capilar/etiología , Síndrome de Fuga Capilar/inmunología , Síndrome de Fuga Capilar/patología , Síndrome de Fuga Capilar/terapia , Diarrea/etiología , Diarrea/inmunología , Diarrea/patología , Diarrea/terapia , Exantema/etiología , Exantema/inmunología , Exantema/patología , Exantema/terapia , Fiebre/etiología , Fiebre/inmunología , Fiebre/patología , Fiebre/terapia , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Insuficiencia Hepática/etiología , Insuficiencia Hepática/inmunología , Insuficiencia Hepática/patología , Insuficiencia Hepática/terapia , Humanos , Linfoma/inmunología , Linfoma/patología , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Síndrome POEMS/inmunología , Síndrome POEMS/patología , Insuficiencia Renal/etiología , Insuficiencia Renal/inmunología , Insuficiencia Renal/patología , Insuficiencia Renal/terapia , Factores de Riesgo , Acondicionamiento Pretrasplante , Trasplante Autólogo
7.
Biol Blood Marrow Transplant ; 19(9): 1368-73, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23806770

RESUMEN

Engraftment syndrome (ES) is an increasingly observed and occasionally fatal complication after autologous peripheral blood stem cell transplantation (PBSCT). In this study, we demonstrate that the incidence of ES is significantly increased in patients undergoing autologous PBSCT for multiple myeloma in comparison to patients with non-Hodgkin lymphoma or Hodgkin lymphoma. Multivariate analysis revealed that age > 60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12 to 2.62; P = .013) and transplantation for multiple myeloma (HR, 2.80; 95% CI, 1.60 to 4.90; P = .0003) were associated with an increased risk of this complication. When stratified for myeloma patients only, age > 60 (HR, 1.80; 95% CI, 1.13 to 2.87; P = .013) and prior treatment with both lenalidomide and bortezomib (HR, 1.83; 95% CI, 1.11 to 3.04; P = .0001) were associated with an increased incidence of ES. Conversely, lack of exposure to cyclophosphamide from either chemomobilization or as a component of the pretransplantation therapeutic regimen increased the risk of this complication (HR, 3.05; 95% CI, 1.91 to 4.87; P <.0001). These studies demonstrate that the pretransplantation exposure of multiple myeloma patients to novel immunomodulatory agents and cyclophosphamide significantly affects the subsequent risk of developing ES.


Asunto(s)
Ciclofosfamida/administración & dosificación , Supervivencia de Injerto/inmunología , Factores Inmunológicos/administración & dosificación , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Supervivencia de Injerto/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Retrospectivos , Trasplante Autólogo , Adulto Joven
8.
Leukemia ; 34(12): 3338-3347, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32313109

RESUMEN

The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance status (KPS) > 90 and ≥very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%). Compared with prior CIBMTR pPCL patients (1995-2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7-21%) in 1995 to 46% (34-64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.


Asunto(s)
Leucemia de Células Plasmáticas/terapia , Adulto , Anciano , Estudios de Cohortes , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia de Células Plasmáticas/cirugía , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Recurrencia , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Trasplante Homólogo/métodos
9.
BMJ Case Rep ; 12(11)2019 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-31767606

RESUMEN

Non-producing variant of plasma cell disorders with circulating plasma cells is an aggressive variant of plasma cell dyscrasias with relatively poor outcomes. A 75-year-old man was admitted due to anaemia (90 g/L) and thrombocytopenia (9×109/L). Comprehensive metabolic panel showed creatinine of 1.34 mg/dL, total protein of 6 g/dL, and corrected calcium was normal. Peripheral smear review showed 8% circulating atypical plasmacytoid cells. Bone marrow biopsy (BMB) confirmed plasma cell myeloma involving 90%-95% of bone marrow cellularity. Serum protein electrophoresis showed no monoclonal protein. Due to aggressive biology of non-producer variant and outcomes based on circulating plasma cells, he was started on VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide) chemotherapy. BMB after cycle 1 chemotherapy showed no morphologic, immunophenotypic, or flow cytometric features of a plasma cell neoplasm. Given excellent treatment response cycle 2 was changed to VRD (bortezomib, lenalidomide and dexamethasone). Following two cycles of VRD, he underwent autologous haematopoietic cell transplantation. Day 80 BMB suggested stringent complete response.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/terapia , Anciano , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Mieloma Múltiple/sangre , Células Plasmáticas/metabolismo
10.
Front Oncol ; 9: 45, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30873378

RESUMEN

Immunomodulatory drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide, have improved survival of patients with multiple myeloma (MM). However, these therapies are associated with an increased risk of venous thromboembolism (VTE). Apixaban has been approved for treatment of acute VTE and for risk reduction of recurrent VTE following initial therapy. In this phase IV single-arm study (NCT02958969), we aim to prospectively evaluate the safety and efficacy of apixaban for primary prevention of VTE in patients with MM. The primary efficacy objective of this trial is to determine the rate of symptomatic VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), over 6 months. The primary safety objective is to determine the rate of major bleeding in MM patients receiving apixaban prophylaxis. If proven safe and effective, apixaban will emerge as a promising option for oral VTE prophylaxis in MM patients.

11.
J Clin Oncol ; 36(9): 859-866, 2018 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-29381435

RESUMEN

Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease). The primary end point was overall response rate (ORR). Results Of 79 patients, 48 had quad-refractory and 31 had penta-refractory myeloma. Patients had received a median of seven prior regimens. The ORR was 21% and was similar for patients with quad-refractory (21%) and penta-refractory (20%) disease. Among patients with high-risk cytogenetics, including t(4;14), t(14;16), and del(17p), the ORR was 35% (six of 17 patients). The median duration of response was 5 months, and 65% of responding patients were alive at 12 months. The most common grade ≥ 3 adverse events were thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue (15%). Dose interruptions for adverse events occurred in 41 patients (52%), dose reductions occurred in 29 patients (37%), and treatment discontinuation occurred in 14 patients (18%). Conclusion The combination of selinexor and dexamethasone has an ORR of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carioferinas/antagonistas & inhibidores , Mieloma Múltiple/tratamiento farmacológico , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Transporte Activo de Núcleo Celular/efectos de los fármacos , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hidrazinas/administración & dosificación , Hidrazinas/efectos adversos , Carioferinas/metabolismo , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Supervivencia sin Progresión , Receptores Citoplasmáticos y Nucleares/metabolismo , Triazoles/administración & dosificación , Triazoles/efectos adversos , Proteína Exportina 1
14.
Case Rep Endocrinol ; 2013: 675298, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24455332

RESUMEN

Purpose. Adrenocorticotropin- (ACTH-) secreting pituitary carcinomas are rare and require multimodality treatment. The aim of this study was to report the response to various therapies and discuss the potential development of secondary adrenal insufficiency with cytotoxic chemotherapy. Methods. This report describes a man with a large silent corticotroph adenoma progressing to endogenous hypercortisolism and metastatic ACTH-secreting pituitary carcinoma over a period of 14 years. Results. Seven years after initial presentation, progressive tumor enlargement associated with the development of hypercortisolism mandated multiple pituitary tumor debulking procedures and radiotherapy. Testing of the Ki-67 proliferation index was markedly high and he developed a hepatic metastasis. Combination therapy with cisplatin and etoposide resulted in a substantial reduction in tumor size, near-complete regression of his liver metastasis, and dramatic decrease in ACTH secretion. This unexpectedly resulted in symptomatic secondary adrenal insufficiency. Conclusions. This is the first reported case of secondary adrenal insufficiency after use of cytotoxic chemotherapy for metastatic ACTH-secreting pituitary carcinoma. High proliferative indices may be predictive of dramatic responses to chemotherapy. Given the potential for such responses, the development of secondary adrenal insufficiency may occur and patients should be monitored accordingly.

15.
Dis Mon ; 58(4): 219-38, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22449370

Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Factores de Edad , Anemia/etiología , Antineoplásicos/uso terapéutico , Proteínas Potenciadoras de Unión a CCAAT/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Diploidia , Coagulación Intravascular Diseminada/etiología , Trasplante de Células Madre Hematopoyéticas , Hepatomegalia/etiología , Humanos , Cariotipo , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/etiología , Leucemia Promielocítica Aguda/clasificación , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/etiología , Leucemia Promielocítica Aguda/terapia , Recuento de Leucocitos , Leucostasis/etiología , Enfermedades Linfáticas/etiología , Mutación , Proteínas Nucleares/genética , Nucleofosmina , Pancitopenia/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Factores de Riesgo , Punción Espinal , Esplenomegalia/etiología , Trombocitopenia/etiología , Translocación Genética , Tirosina Quinasa 3 Similar a fms/genética , Proteína ETS de Variante de Translocación 6
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