Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.464
Filtrar
1.
Rinsho Ketsueki ; 61(3): 274-279, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-32224590

RESUMEN

A 46-year-old female patient underwent a cord blood transplantation (conditioning regimen: fludarabine/busulfan4/melphalan80; graft-versus-host disease (GVHD) prophylaxis: tacrolimus + mycophenolate mofetil) for acute myeloid leukemia (AML) with her 1st hematological complete response to induction therapy (idarubicin 3 days+cytarabine 7 days). She lost her consciousness due to human herpesvirus 6 (HHV-6) encephalitis on day 31, and therefore, we increased the foscarnet dosage (from 120 mg/kg to 180 mg/kg). Her consciousness level improved after treatment. However, 8 hours of sudden hypothermia occurred with hyperhidrosis, hypertension, and subsequent hyperglycemia on day 34. Her condition did not improve even after administration of anticonvulsant, steroid pulse, or intravenous immunoglobulin. A total of 75 attacks were observed until she was discharged on day 471. She has not shown chronic GVHD or relapsed AML since then. However, HHV-6 caused prolonged damage to her hypothalamus as observed through magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) using 99mTc ethyl cysteinate dimer even when the virus was not detected from her cerebrospinal fluid. This damage can be responsible for the hypothermia attacks. This is the first case report of prolonged series of hypothermia attacks for over a year as a sequela of HHV-6 encephalitis after a cord blood transplantation for AML.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 6 , Hipotermia , Leucemia Mieloide Aguda , Encefalitis Viral , Femenino , Humanos , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Infecciones por Roseolovirus , Acondicionamiento Pretrasplante , Trasplante Homólogo
2.
Zhonghua Xue Ye Xue Za Zhi ; 41(2): 106-111, 2020 Feb 14.
Artículo en Chino | MEDLINE | ID: mdl-32135625

RESUMEN

Objective: To analyze the risk factors of steroid resistant acute graft- versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of adult patients with acute myeloid leukemia (AML) /Myelodysplastic syndrome (MDS) who developed aGVHD after haplo-HSCT in Peking University Institute of Hematology from January 1st, 2010 to December 31st, 2012 were retrospectively reviewed. Results: A total of 85 patients were enrolled in the study, including 55 males and 30 females, with a median age of 30 (19-67) years. After steroid therapy, there were 53 (62.4%) , 6 (7.1%) and 26 (30.6%) patients achieved complete remission (CR) , partial remission (PR) and non-remission (NR) , respectively. The CR rates of the grade Ⅰ/Ⅱ and Ⅲ/Ⅳ aGVHD by steroid therapy were 66.2% (51/77) vs 25.0% (2/8) (χ(2)=3.639, P=0.048) , respectively. The CR rates of the patients with aGVHD involving 1 target organ and 2 target organs were 77.4% (48/62) vs 21.7% (5/23) (χ(2)=22.157, P<0.001) . The CR rates of patients with standard risk (SR) and high risk (HR) Minnesota risk score was 67.5% (52/77) vs 12.5% (1/8) (χ(2)=7.153, P=0.004) . The mononuclear cells≥8.33×10(8)/kg and the HR Minnesota risk score were independent risk factors for steroid-resistant aGVHD in multivariate analysis. Between Minnesota risk score SR (77 cases) and HR (8 cases) groups, the OS rates at 22 months after transplantation were (90.3±3.8) %vs (75.0±15.3) % (χ(2)=2.831, P=0.092) . After steroid treatment for aGVHD, the OS rates at 22 months in the CR group (53 cases) and non-CR group (32 cases) were (95.2±3.4) %vs (78.6±7.9) % (χ(2)=5.287, P=0.021) respectively. Conclusion: The Minnesota risk score and mononuclear cells count are effective tool for predicting steroid-resistant aGVHD after haplo-HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
3.
Zhonghua Xue Ye Xue Za Zhi ; 41(1): 16-22, 2020 Jan 14.
Artículo en Chino | MEDLINE | ID: mdl-32023749

RESUMEN

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR(1)) and negative minimal residual disease (MRD(-)) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR(1)/MRD(-) from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR(1)/MRD(-) was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion: Allo-HSCT for candidate patients without further consolidation when CR(1)/MRD(-) was attained was feasible.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Anciano , Humanos , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Neoplasia Residual , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Adulto Joven
4.
Ann Hematol ; 99(4): 855-866, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32036420

RESUMEN

This retrospective single-center analysis studied the impact of the conditioning and the graft-versus-host disease (GVHD) prophylaxis on outcome in unselected patients allografted for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) secondary to documented prior CMML. A total of 44 patients (median age 61 years) allografted between 2002 and 2019 in our institution were analyzed. Fifteen patients had secondary AML. The conditioning regimen was fractionated 6-8 Gy total body irradiation (TBI) in combination with fludarabine in 33 (75%) patients. Eleven patients (25%) received alkylator-based conditioning therapy without TBI. For GVHD prophylaxis, a calcineurin inhibitor (CNI) backbone in combination with methotrexate (MTX) or mycophenolate mofetil (MMF) was applied in 21 and 23 patients, respectively. All patients allografted from an unrelated donor (UD) received antithymocyte globuline. In univariate analysis of the entire cohort, TBI-based conditioning and MMF-containing immunosuppression were associated with improved leukemia-free survival (LFS, HR 0.16, P < 0.001 and HR 0.41, P = 0.030, respectively). After stratification according to conditioning and GVHD prophylaxis into four groups (TBI-MMF [n = 17], TBI-MTX [n = 16], alkylator-MMF [n = 6], alkylator-MTX [n = 5]), TBI-MMF was associated with improved overall survival (OS) and LFS (P = 0.001 and P < 0.001, respectively). Patient and disease characteristics did not differ between the groups. The associations of TBI-based conditioning and MMF with prolonged LFS were observed across the CMML (n = 29), secondary AML (n = 15), and UD allograft (n = 34) subgroups. In summary, our study suggests that allografting based on intermediate-dose TBI conditioning and MMF-containing GVHD prophylaxis is associated with increased disease control in CMML. Larger (registry-based) studies are warranted to confirm our findings.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/uso terapéutico , Leucemia Mielomonocítica Crónica/terapia , Ácido Micofenólico/uso terapéutico , Agonistas Mieloablativos/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/terapia , Masculino , Melfalán/uso terapéutico , Metotrexato/uso terapéutico , Persona de Mediana Edad , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Linfocitos T/inmunología , Trasplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
5.
Ann Hematol ; 99(4): 773-780, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32088745

RESUMEN

Although complete remission (CR) is achieved in 50 to 70% of older fit patients with acute myeloid leukemia (AML), consolidation therapy in this age group remains challenging. In this retrospective study, we aimed to compare outcome in elderly patients treated with different post-remission modalities, including allogenic and autologous hematopoietic stem cell transplantation (HSCT), intensive chemotherapy, and standard-dose chemotherapy (repeated 1 + 5 regimen). We collected data of 441 patients ≥ 60 years in first CR from a single institution. Median age was 67 years. Sixty-one (14%) patients received allo-HSCT, 51 (12%) auto-HSCT, 70 (16%) intensive chemotherapy with intermediate- or high-dose cytarabine (I/HDAC), and 190 (43%) 1 + 5 regimen. Median follow-up was 6.5 years. In multivariate analysis, allo-HSCT, cytogenetics, and PS had a significant impact on OS and LFS. In spite of a more favorable-risk profile, the patients who received I/HDAC had no significantly better LFS as compared with patients treated with 1 + 5 (median LFS 8.8 months vs 10.6 months, p = 0.96). In transplanted patients, median LFS was 13.3 months for auto-HSCT and 25.8 months for allo-HSCT. Pre-transplant chemotherapy with I/HDAC had no effect on the outcome. Toxicity was significantly increased for both transplanted and non-transplanted patients treated with I/HDAC, with more units of blood and platelet transfusion and more time spent in hospitalization, but no higher non-relapse mortality. This study shows that post-remission chemotherapy intensification is not associated with significantly better outcome as compared with standard-dose chemotherapy in elderly patients for whom, overall results remain disappointing.


Asunto(s)
Quimioterapia de Consolidación , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Aloinjertos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión de Componentes Sanguíneos , Terapia Combinada , Citarabina/administración & dosificación , Citarabina/efectos adversos , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
6.
Adv Exp Med Biol ; 1232: 415-420, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31893439

RESUMEN

Murine models have become powerful tools in leukemia research for investigating interactions between blast cells niche factors. In the tumor microenvironment, immune cells are one of the most important niche factors, capable of mounting dynamic innate or adoptive responses against leukemic cells. Acute myeloid leukemia (AML) is a systemic cancer accompanied by immune disruption. In order to exploit the enhanced activity of immune cells in AML treatment, the use of syngeneic mouse models is necessary. Studies of crosstalk between cancer blast cells and immune cells in syngeneic mouse models are beneficial, as the absence of immune functions in syngeneic models enables focus on cancer-associated immune reactions. Once AML is induced, innate and adoptive immune cells respond differently, ultimately resulting in suppression of the immune cells. Murine AML models are commonly induced by intravenous or subcutaneous injection of C1498 cells. Despite the popularity of murine models, they have not yet resulted in the elucidation of distinct differences in immune cells by the injection method. Here, we investigated the frequency of immune cells and survival rate of mice with AML induced using both injection methods.


Asunto(s)
Leucemia Mieloide Aguda , Animales , Modelos Animales de Enfermedad , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Ratones , Microambiente Tumoral/inmunología
7.
Nat Rev Cancer ; 20(3): 158-173, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31907378

RESUMEN

For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell field. In CML, the acquisition of the fusion tyrosine kinase BCR-ABL1 in a haematopoietic stem cell drives its transformation to become a LSC. In AML, LSCs can arise from multiple cell types through the activity of a number of oncogenic drivers and pre-leukaemic events, adding further layers of context and genetic and cellular heterogeneity to AML LSCs not observed in most cases of CML. Furthermore, LSCs from both AML and CML can be refractory to standard-of-care therapies and persist in patients, diversify clonally and serve as reservoirs to drive relapse, recurrence or progression to more aggressive forms. Despite these complexities, LSCs in both diseases share biological features, making them distinct from other CML or AML progenitor cells and from normal haematopoietic stem cells. These features may represent Achilles' heels against which novel therapies can be developed. Here, we review many of the similarities and differences that exist between LSCs in CML and AML and examine the therapeutic strategies that could be used to eradicate them.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/metabolismo , Células Madre Neoplásicas/metabolismo , Animales , Biomarcadores de Tumor , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Desarrollo de Medicamentos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Terapia Molecular Dirigida , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Investigación/historia , Investigación/tendencias
8.
Ann Hematol ; 99(3): 459-475, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31932899

RESUMEN

Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by a collection of genetic and epigenetic changes. As a consequence, AML can evolve towards more aggressive subtypes during treatment, which require additional therapies to prevent future relapse. As we have previously detected double-stranded DNA (dsDNA) in tumor-derived extracellular vesicles (EVs), in this current study we attempted to evaluate the potential diagnostic applications of AML EV-dsDNA derived from primary bone marrow and peripheral blood plasma samples. EVs from plasma of 29 pediatric AML patients (at initial diagnosis or during treatment) were isolated by ultracentrifugation, after which dsDNA was extracted from obtained EVs and analyzed for leukemia-specific mutations using next generation sequencing (NGS) and GeneScan-based fragment-length analysis. In 18 out of 20 patients, dsDNA harvested from EVs mirrored the (leukemia-specific) mutations found in the genomic DNA obtained from primary leukemia cells. In the nanoparticle tracking analysis (NTA), a decrease in EV numbers was observed in patients after treatment compared with initial diagnosis. Following treatment, in 75 samples out of the 79, these mutations were no longer detectable in EV-dsDNA. In light of our results, we propose the use of leukemia-derived EV-dsDNA as an additional measure for mutational status and, potentially, treatment response in pediatric AML.


Asunto(s)
ADN de Neoplasias , Vesículas Extracelulares , Leucemia Mieloide Aguda , Mutación , Adolescente , Niño , Preescolar , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Masculino
9.
Internist (Berl) ; 61(2): 175-184, 2020 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-31925478

RESUMEN

Myelodysplastic syndromes (MDS)-previously called "preleukemias"-are clonal diseases of the pluripotent hematopoietic stem cell. Their hallmark is peripheral cytopenias. Early forms are characterized by dysplasia of mature cells in the peripheral blood or erythropoiesis, granulopoiesis or megakaryocytes in the bone marrow, and later stages tend to accumulate blasts. About 30% transform into acute myeloid leukemia. MDS are diseases of the elderly and are prognostically divided into lower and higher risk diseases. Median survival times vary accordingly between 6 months and 10 years. Chromosomal abnormalities are identified in 50% of patients, and single or multiple gene mutations occur in 80%. They are the driving force leading to abnormalities in differentiation and to the accumulation of blasts in the bone marrow. Therapeutic options include supportive care, erythropoiesis-stimulating agents, demethylating agents, and allogeneic stem cell transplantation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Anciano , Médula Ósea , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/terapia , Pronóstico
10.
Nat Commun ; 11(1): 400, 2020 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-31964864

RESUMEN

Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving bone marrow ablation followed by hematopoietic stem cell transplantation in multiple myeloma and acute myeloid leukemia patients indicate that cf-mRNA levels reflect the transcriptional activity of bone marrow-resident hematopoietic lineages during bone marrow reconstitution. Mechanistically, stimulation of specific bone marrow cell populations in vivo using growth factor pharmacotherapy show that cf-mRNA reflects dynamic functional changes over time associated with cellular activity. Our results shed light on the biology of the circulating transcriptome and highlight the potential utility of cf-mRNA to non-invasively monitor bone marrow involved pathologies.


Asunto(s)
Biomarcadores de Tumor/aislamiento & purificación , Médula Ósea/patología , Ácidos Nucleicos Libres de Células/aislamiento & purificación , Leucemia Mieloide Aguda/diagnóstico , Mieloma Múltiple/diagnóstico , ARN Mensajero/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Médula Ósea/efectos de los fármacos , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Estudios de Factibilidad , Perfilación de la Expresión Génica/métodos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Estudios Longitudinales , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , ARN Mensajero/sangre , ARN Mensajero/genética , Análisis de Secuencia de ARN/métodos , Resultado del Tratamiento , Adulto Joven
11.
Ann Hematol ; 99(1): 147-155, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31786646

RESUMEN

Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT.


Asunto(s)
Suero Antilinfocítico/administración & dosificación , Efecto Injerto vs Leucemia , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Depleción Linfocítica , Metilprednisolona/administración & dosificación , Adolescente , Adulto , Anciano , Aloinjertos , Ciclofosfamida/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia Mieloide Aguda/sangre , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras , Recurrencia
12.
Ann Hematol ; 99(2): 385-388, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31773213

Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/tratamiento farmacológico , Terapia Molecular Dirigida , Neoplasias Primarias Secundarias/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Aloinjertos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/etiología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/etiología , Humanos , Inmunosupresores/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/terapia , Masculino , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Protoporfiria Eritropoyética/terapia , Recurrencia , Inducción de Remisión , Activación Viral , Adulto Joven
13.
Hematol Oncol ; 38(1): 74-81, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31755141

RESUMEN

High levels of acute phase reactants can be associated with adverse outcome in patients with various solid tumor types. For patients with acute myeloid leukemia (AML), this correlation is unknown. We retrospectively investigated the prognostic value of pretreatment acute phase protein levels in 282 consecutive newly diagnosed AML patients undergoing at least one cycle of intensive induction chemotherapy. We applied a new score integrating pre-treatment C-reactive protein (CRP), fibrinogen, and albumin levels termed the CFA ratio, and we stratified patients into two groups: Patients with a CFA ratio below 3.06 had decisively better progression-free (26.2 vs 7.7 months; P < .001), disease-free (56.4 vs 8.7 months; P < .001), and overall survival (61.2 vs 13.8 months; P < .001). Results remained significant when adjusting for confounders including European Leukemia Network risk group. Early mortality also tended to be lower in the low CFA ratio group. Finally, patients with lower modified Glasgow prognostic score (mGPS) similarly had better outcome. In conclusion, our data suggest that an elevated CFA ratio as well as a high mGPS are associated with adverse outcome in patients with newly diagnosed AML undergoing intensive induction. These parameters should undergo prospective evaluation for their contribution to risk profiling in AML patients.


Asunto(s)
Proteínas de Fase Aguda/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Trasplante de Células Madre Hematopoyéticas/mortalidad , Quimioterapia de Inducción/mortalidad , Leucemia Mieloide Aguda/mortalidad , Adulto , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo , Adulto Joven
14.
Lancet Haematol ; 7(1): e28-e39, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31606445

RESUMEN

BACKGROUND: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. METHODS: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18-70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts <5% in bone marrow) or myelodysplastic syndrome (blast counts <20% in bone marrow), Karnofsky index of 60% or higher, and were indicated for allogeneic HSCT but considered at an increased risk for standard myeloablative preparative regimens based on age (≥50 years), an HSCT-specific comorbidity index of more than 2, or both. Patients were randomly assigned (1:1) to receive either intravenous 10 g/m2 treosulfan daily applied as a 2-h infusion for 3 days (days -4 to -2) or 0·8 mg/kg busulfan applied as a 2-h infusion at 6-h intervals on days -4 and -3. Both groups received 30 mg/m2 intravenous fludarabine daily for 5 days (days -6 to -2). The primary outcome was event-free survival 2 years after HSCT. The non-inferiority margin was a hazard ratio (HR) of 1·3. Efficacy was assessed in all patients who received treatment and completed transplantation, and safety in all patients who received treatment. The study is registered with EudraCT (2008-002356-18) and ClinicalTrials.gov (NCT00822393). FINDINGS: Between June 13, 2013, and May 3, 2016, 476 patients were enrolled (240 in the busulfan group received treatment and transplantation, and in the treosulfan group 221 received treatment and 220 transplanation). At the second preplanned interim analysis (Nov 9, 2016), the primary endpoint was met and trial was stopped. Here we present the final confirmatory analysis (data cutoff May 31, 2017). Median follow-up was 15·4 months (IQR 8·8-23·6) for patients treated with treosulfan and 17·4 months (6·3-23·4) for those treated with busulfan. 2-year event-free survival was 64·0% (95% CI 56·0-70·9) in the treosulfan group and 50·4% (42·8-57·5) in the busulfan group (HR 0·65 [95% CI 0·47-0·90]; p<0·0001 for non-inferiority, p=0·0051 for superiority). The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (33 [15%] of 221 patients in the treosulfan group vs 35 [15%] of 240 patients in the busulfan group) and gastrointestinal disorders (24 [11%] patients vs 39 [16%] patients). Serious adverse events were reported for 18 (8%) patients in the treosulfan group and 17 (7%) patients in the busulfan group. Causes of deaths were generally transplantation-related. INTERPRETATION: Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. The improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population. FUNDING: medac GmbH.


Asunto(s)
Antineoplásicos/uso terapéutico , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vidarabina/uso terapéutico
15.
Am J Hematol ; 95(3): 282-294, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31876307

RESUMEN

Monosomy 7 or deletion 7q (-7/7q-) is the most frequent adverse cytogenetic features reported in acute myeloid leukemia (AML), and is a common indication for allogeneic stem cell transplantation (SCT). Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion of chromosome 3 (inv(3)), the presence of which may influence the outcomes after SCT. A total of 1109 patients were allocated to this study. Two-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. Two-year probability of non-relapse mortality (NRM) was 20%. We defined five different cytogenetic subgroups: the "-7/7q- ± CK group- designated group1," the "MK group-designated group 2," the "-5/5q- group- designated group 3," the "abn(17p) group- designated group 4" and the "inv(3) group- designated group 5." The 2-year probability of LFS in first remission was 48% for group 1, 36.4% for group 2, 28.4% for group 3, 19.1% for group 4 and 17.3% for group 5, respectively (P < .001). Multivariate analysis confirmed those significant differences across groups. Note, SCT in -7/7q- AML provides durable responses in one third of the patients. The presence of -7/7q- with or without CK in the absence of MK, abn(17p) or inv(3) is associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of patients with poor prognosis even after SCT.


Asunto(s)
Leucemia Mieloide Aguda , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Aloinjertos , Deleción Cromosómica , Cromosomas Humanos Par 7/genética , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Prueba de Histocompatibilidad , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia
16.
Am J Hematol ; 95(1): 48-56, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31637757

RESUMEN

Clofarabine is an immunosuppressive purine nucleoside analog that may have better anti-leukemic activity than fludarabine. We performed a prospective phase I/II multisite trial of clofarabine with 2 Gy total body irradiation as non-myeloablative conditioning for allogeneic hematopoietic cell transplantation in adults with acute myeloid leukemia who were unfit for more intense regimens. Our main objective was to improve the 6-month relapse rate following non-myeloablative conditioning, while maintaining historic rates of non-relapse mortality (NRM) and engraftment. Forty-four patients, 53 to 74 (median: 69) years, were treated with clofarabine at 150 to 250 mg/m2 , of whom 36 were treated at the maximum protocol-specified dose. One patient developed multifactorial acute kidney injury and another developed multiorgan failure, but no other grade 3 to 5 non-hematologic toxicities were observed. All patients fully engrafted. The 6-month relapse rate was 16% (95% CI, 5%-27%) among all patients and 14% (95% CI, 3%-26%) among high-risk patients treated at the maximum dose, meeting the pre-specified primary efficacy endpoint. Overall survival was 55% (95% CI, 40%-70%) and leukemia-free survival was 52% (95% CI, 37%-67%) at 2 years. Compared to a historical high-risk cohort treated with the combination of fludarabine at 90 mg/m2 and 2 Gy TBI, protocol patients treated with the clofarabine-TBI regimen had lower rates of overall mortality (HR of 0.50, 95% CI, 0.28-0.91), disease progression or death (HR 0.48, 95% CI, 0.27-0.85), and morphologic relapse (HR 0.30, 95% CI, 0.13-0.69), and comparable NRM (HR 0.85, 95% CI 0.36-2.00). The combination of clofarabine with TBI warrants further investigation in patients with high-risk AML.


Asunto(s)
Clofarabina/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total/métodos , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Análisis de Supervivencia , Resultado del Tratamiento
17.
Lancet Haematol ; 7(3): e238-e246, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31879230

RESUMEN

BACKGROUND: Data to inform surveillance and treatment for leukaemia predisposition syndromes are scarce and recommendations are largely based on expert opinion. This study aimed to investigate the clinical features and outcomes of patients with myelodysplastic syndrome or acute myeloid leukaemia and Shwachman-Diamond syndrome, an inherited bone marrow failure disorder with high risk of developing myeloid malignancies. METHODS: We did a multicentre, retrospective, cohort study in collaboration with the North American Shwachman-Diamond Syndrome Registry. We reviewed patient medical records from 17 centres in the USA and Canada. Patients with a genetic (biallelic mutations in the SBDS gene) or clinical diagnosis (cytopenias and pancreatic dysfunction) of Shwachman-Diamond syndrome who developed myelodysplastic syndrome or acute myeloid leukaemia were eligible without additional restriction. Medical records were reviewed between March 1, 2001, and Oct 5, 2017. Masked central review of bone marrow pathology was done if available to confirm leukaemia or myelodysplastic syndrome diagnosis. We describe the clinical features and overall survival of these patients. FINDINGS: We initially identified 37 patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia. 27 patients had samples available for central pathology review and were reclassified accordingly (central diagnosis concurred with local in 15 [56%] cases), 10 had no samples available and were classified based on the local review data, and 1 patient was excluded at this stage as not eligible. 36 patients were included in the analysis, of whom 10 (28%) initially presented with acute myeloid leukaemia and 26 (72%) initially presented with myelodysplastic syndrome. With a median follow-up of 4·9 years (IQR 3·9-8·4), median overall survival for patients with myelodysplastic syndrome was 7·7 years (95% CI 0·8-not reached) and 0·99 years (95% CI 0·2-2·4) for patients with acute myeloid leukaemia. Overall survival at 3 years was 11% (95% CI 1-39) for patients with leukaemia and 51% (29-68) for patients with myelodysplastic syndrome. Management and surveillance were variable. 18 (69%) of 26 patients with myelodysplastic syndrome received upfront therapy (14 haematopoietic stem cell transplantation and 4 chemotherapy), 4 (15%) patients received no treatment, 2 (8%) had unavailable data, and 2 (8%) progressed to acute myeloid leukaemia before receiving treatment. 12 patients received treatment for acute myeloid leukaemia-including the two patients initially diagnosed with myelodysplastic who progressed- two (16%) received HSCT as initial therapy and ten (83%) received chemotherapy with intent to proceed with HSCT. 33 (92%) of 36 patients (eight of ten with leukaemia and 25 of 26 with myelodysplastic syndrome) were known to have Shwachman-Diamond syndrome before development of a myeloid malignancy and could have been monitored with bone marrow surveillance. Bone marrow surveillance before myeloid malignancy diagnosis was done in three (33%) of nine patients with leukaemia for whom surveillance status was confirmed and 11 (46%) of 24 patients with myelodysplastic syndrome. Patients monitored had a 3-year overall survival of 62% (95% CI 32-82; n=14) compared with 28% (95% CI 10-50; n=19; p=0·13) without surveillance. Six (40%) of 15 patients with available longitudinal data developed myelodysplastic syndrome in the setting of stable blood counts. INTERPRETATION: Our results suggest that prognosis is poor for patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia owing to both therapy-resistant disease and treatment-related toxicities. Improved surveillance algorithms and risk stratification tools, studies of clonal evolution, and prospective trials are needed to inform effective prevention and treatment strategies for leukaemia predisposition in patients with Shwachman-Diamond syndrome. FUNDING: National Institute of Health.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia Mieloide Aguda/mortalidad , Síndromes Mielodisplásicos/mortalidad , Síndrome de Shwachman-Diamond/mortalidad , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/terapia , Pronóstico , Estudios Retrospectivos , Síndrome de Shwachman-Diamond/patología , Síndrome de Shwachman-Diamond/terapia , Tasa de Supervivencia , Adulto Joven
18.
Cancer Metastasis Rev ; 38(4): 829-837, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31802358

RESUMEN

Matrix metalloproteinases (MMPs) play a major role in extracellular matrix remodeling and are involved in tumor cell invasion. Cancers such as childhood leukemia are characterized by their capacity to infiltrate different organs. MMP production by leukemic cells may indicate a leukemic subtype or subpopulation with a more invasive phenotype. Therefore, clarifying the action mechanisms of MMPs as prognostic predictors or MMP targeting as a therapeutic strategy is necessary. MMP-targeting drugs have been developed for the treatment of hematological malignancies. In this review, we highlight current advances in understanding the molecular mechanisms and pathological characteristics of various MMPs, as well as recent therapeutic advances targeting MMPs in childhood leukemia. Several studies have been conducted on the therapeutic efficacy of MMP inhibitors in cancer, such as collagen peptidomimetics, nonpeptidomimetic inhibitors of MMP active sites, bisphosphonates, and tetracycline derivatives. Here, we conclude that more clinical trials are necessary to estimate the role of selective MMP inhibitors in the treatment and prevention of childhood leukemia.


Asunto(s)
Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/terapia , Metaloproteinasas de la Matriz/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animales , Niño , Humanos
19.
Medicine (Baltimore) ; 98(50): e18196, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852076

RESUMEN

This study aimed at investigating the prevalence of anxiety and depression, and their risk factors as well as their correlation with prognosis in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients.A total of 180 R/R AML patients were enrolled and their anxiety and depression were assessed by Hospital Anxiety and Depression Scale (HADS) before treatment. Besides, HADS was also evaluated in 180 de novo AML patients prior treatment and 180 healthy controls (HCs), respectively.Both the HADS-Anxiety and HADS-Depression scores were increased in R/R AML patients compared with de novo AML patients and HCs (all P < .001). Meanwhile, the prevalence of anxiety and depression was 53.9% and 45.6% in R/R AML patients, which were also greatly higher compared with de novo AML patients and HCs (all P < .01). Regarding risk factors, higher Eastern Cooperative Oncology Group score and lines of salvage therapy were correlated with anxiety and depression in R/R AML patients (all P < .05). Furthermore, anxiety and depression were associated with shorter overall survival (OS) in R/R AML patients (all P < .05), while no association of different degrees of anxiety and depression with OS was observed (all P > .05).Anxiety and depression are highly prevalent and implicated in the management and prognosis of R/R AML.


Asunto(s)
Ansiedad/etiología , Depresión/epidemiología , Leucemia Mieloide Aguda/complicaciones , Inducción de Remisión/métodos , Medición de Riesgo/métodos , Ansiedad/epidemiología , China/epidemiología , Terapia Combinada , Depresión/etiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
20.
Medicine (Baltimore) ; 98(52): e18390, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31876710

RESUMEN

RATIONALE: Granulocytic sarcoma (GS), also known as chloroma, is a tumor comprising myeloblasts or monoblasts, potentially occurring as an extramedullary mass. Systemic chemotherapy should be used to induce complete remission. However, such patients with chloroma have a poorer treatment outcome than those without extramedullary myeloid sarcomas. PATIENT CONCERNS: A 30-year-old woman who initially presented with bilateral ovarian masses and splenomegaly was admitted to hospital. Also, her complete blood cell counts showed pancytopenia and blood smear revealed a few immature cells (3%). DIAGNOSES: A bone marrow biopsy demonstrated acute myelomonocytic leukemia, and the chromosomal analysis revealed a 46, XX, del18 (p11) [20] karyotype and cytogenetics and molecular markers showed all negative results. INTERVENTIONS: Since this diagnosis, she received remission-inducing chemotherapy comprising anthracycline and cytarabine, which is a standard regimen for acute myeloid leukemia (AML), and followed by allogenic hematopoietic stem cell transplantation from Human leukocyte antigen (HLA)-identical sibling donor. OUTCOMES: After transplantation, the bone marrow engrafted successfully without complications. She visited our clinic regularly with no evidence of leukemia relapse or graft-versus host disease. LESSONS: This report represents the first case of ovarian GS, wherein treatment was successful with high-dose chemotherapy, followed by allogenic hematopoietic stem cell transplantation without oophorectomy.


Asunto(s)
Leucemia Mieloide Aguda/terapia , Neoplasias Ováricas/etiología , Sarcoma Mieloide/etiología , Trasplante de Células Madre , Adulto , Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Femenino , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/terapia , Sarcoma Mieloide/tratamiento farmacológico , Sarcoma Mieloide/terapia , Trasplante de Células Madre/métodos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA