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1.
Ther Drug Monit ; 41(5): 575-581, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31008998

RESUMEN

BACKGROUND: Tyrosine kinase inhibitors markedly improve the survival for patients with chronic myeloid leukemia (CML). However, a decrease in adherence leads to undesired therapeutic outcomes. In this study, the relationships among adherence, pharmacokinetics, response, and adverse effects for dasatinib treatment were prospectively investigated. METHODS: This study was a prospective cohort study of patients with newly diagnosed CML at 4 general hospitals and 1 university hospital. Patients started to receive dasatinib 100 mg once daily. A Medication Event Monitoring System was used to assess medication adherence and the medication possession ratio during the 12 months. Plasma concentrations of dasatinib were measured using liquid chromatograph-tandem mass spectrometry (LC-MS/MS), and therapy responses were assessed at 3, 6, and 12 months after treatment. RESULTS: Ten patients were included. An extremely high medication adherence for dasatinib was observed; the median medication possession ratio was 99.4%. All 9 CML patients with breakpoints in the major BCR-ABL achieved major molecular response (MMR; major BCR-ABL transcript level below 0.1% on the International Scale) within 12 months, and 5 achieved MMR within 6 months. The receiver operating characteristic curve analysis revealed that the cutoff value for the dasatinib area under the concentration-time curve was 336.1 ng × h/mL (accuracy 88.9%, sensitivity 80.0%, specificity 100%, and receiver operating characteristic curve-area under the concentration-time curve 0.800) for achieving MMR within 6 months. Two patients had interrupted dasatinib treatment because of pleural effusion and diarrhea with intestinal edema, respectively. These edematous adverse events developed after plasma dasatinib Cmin surpassed 3.0 ng/mL. CONCLUSIONS: A Medication Event Monitoring System was applied for the direct evaluation of oral dasatinib adherence for the first time, and the clinical effect of dasatinib was investigated under the strict monitoring of patient adherence. Although this study had a small sample size, the plasma concentration monitoring of dasatinib is considered to be useful to predict an earlier molecular response with fewer edematous adverse events.


Asunto(s)
Dasatinib/farmacocinética , Dasatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Cromatografía Liquida/métodos , Femenino , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Espectrometría de Masas en Tándem/métodos
2.
Ann Hematol ; 97(9): 1535-1545, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29694642

RESUMEN

The Japan Adult Leukemia Study Group (JALSG) Ph+ALL202 study reported a high complete remission (CR) rate for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients treated with imatinib-combined chemotherapy. However, the long-term treatment efficacy remains uncertain. Here, we report a final analysis of the JALSG Ph+ALL202 study. The outcomes were compared with those of the JALSG ALL93 and ALL97 studies, which were conducted in the pre-imatinib era. Ninety-nine newly diagnosed Ph+ALL patients were enrolled in Ph+ALL202 (median age, 45 years; median follow-up, 4.5 years). CR was achieved in 96/99 (97%) patients. Fifty-nine of these 96 patients (61%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in their first CR (CR1). The 5-year overall and disease-free survival (DFS) rates were 50 and 43%, respectively, which were significantly higher compared to those in the pre-imatinib era (15 and 19%, respectively). Multivariate analysis revealed that imatinib administration, allo-HSCT in CR1, and a white blood cell count < 30 × 109/L were favorable independent prognostic factors for long-term DFS. Improved odds of receiving allo-HSCT and a lower relapse rate leaded to good long-term outcomes. The 3-year DFS tended to be higher in PCR-negative than that in PCR-positive patients (29 vs. 14%) in the non-HSCT patients, and this tendency was also seen in the allo-HSCT patients (59 vs. 50%). The higher rate of CR upon imatinib use may have contributed to these improvements.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Inhibidores de Proteínas Quinasas/administración & dosificación , Adolescente , Adulto , Estudios de Cohortes , Terapia Combinada , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Mesilato de Imatinib/uso terapéutico , Japón/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas/efectos adversos , Inducción de Remisión , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
3.
Rinsho Ketsueki ; 58(7): 766-771, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-28781272

RESUMEN

Chronic myeloid leukemia (CML) typically causes leukocytosis rather than thrombocytosis. We encountered two women in their thirties with remarkable thrombocytosis, whose platelet counts were over 3,000×103/µl, and without significant leukocytosis. Although their clinical findings resembled that of essential thrombocythemia (ET), they were diagnosed with CML because of the presence of Philadelphia chromosome. JAK2, CALR, and MPL were unmutated. On fluorescence in situ hybridization analysis, only 19.8% of granulocytes in case 2 were found to be BCR/ABL positive in peripheral blood (PB). We reviewed 11 CML cases whose platelet counts were over 2,000×103/µl, but their WBC counts were not significantly elevated (<12,000/µl). Most of them were young females with a normal or a high neutrophil alkaline phosphatase score and without immature myeloid cells in PB. These findings suggested that there is a subgroup of CML patients with marked thrombocytosis and without significant leukocytosis, which may be misdiagnosed as ET.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Trombocitosis/etiología , Adulto , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 9 , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucocitosis , Embarazo , Complicaciones Hematológicas del Embarazo , Complicaciones Neoplásicas del Embarazo
4.
Ther Drug Monit ; 37(5): 581-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25565672

RESUMEN

BACKGROUND: Blood tacrolimus (TAC) concentration delivered via intravenous administration is known to be influenced by genetic polymorphism of CYP3A5 and interaction with triazole antifungal agents. However, interindividual variability of blood TAC concentration is as of yet still difficult to predict during the early stages of hematopoietic stem cell transplantation (HSCT). This study was conducted to assess the wide variability of blood TAC concentrations because of the hepatic metabolic activities of CYP3A and CYP2C19 in HSCT recipients. METHODS: This study is a single-institute prospective study that includes 21 adult patients who underwent HSCT and received 24 hours continuous intravenous administration of TAC at the Mie University Hospital between January 2009 and March 2014. After HSCT, the changes in blood TAC concentration/dose (C/D) ratio and TAC dose reduction from initial dose were investigated. RESULTS: Significant differences between HSCT recipients with CYP3A5*1 allele and CYP3A5*3/*3 genotype were observed with respect to the median TAC C/D ratio on day 14 (563 versus 742 ng/mL per mg/kg, P < 0.01) and day 21 (672 versus 777 ng/mL per mg/kg, P < 0.05) after HSCT. Concomitant administration of voriconazole (VRCZ), but not of lansoprazole, was found to significantly increase the median TAC C/D ratio on day 14 (557 versus 723 ng/mL per mg/kg, P < 0.01). Possession of the CYP3A5*3/*3 genotype (day 14: odds ratio, 32.2; day 21: odds ratio, 33.0; P < 0.05) and concomitant administration of VRCZ (day 14: odds ratio, 37.8; P < 0.05) were found to be independent risk factors, which significantly contributed to an increased TAC C/D ratio. In HSCT recipients with CYP3A5*3/*3 genotype (78.0%), the median TAC dose ratio (day 21/day -1) was significantly lower compared with HSCT recipients with the CYP3A5*1 allele (94.1%), whereas VRCZ administration itself had no significant influence. Interestingly, in HSCT recipients with CYP2C19*1/*1, we found that the influence of VRCZ on the TAC dose ratio (85.7%) was relatively mild, even in a recipient with CYP3A5*3/*3. CONCLUSIONS: In HSCT recipients, the variability of intravenous TAC concentration in the blood could be explained in part by the genetic variation of CYP3A5. The study results also strongly imply that the magnitude of hepatic interaction between TAC and VRCZ is affected by the genetic polymorphism of both CYP3A5 and CYP2C19 genes.


Asunto(s)
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Trasplante de Células Madre Hematopoyéticas , Polimorfismo Genético , Tacrolimus/sangre , Voriconazol/farmacología , Adolescente , Adulto , Interacciones Farmacológicas , Femenino , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
5.
Rinsho Ketsueki ; 56(8): 1076-81, 2015 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-26345570

RESUMEN

A 36-year-old woman complained of a mass on the sole of her foot in February 200X. She was diagnosed with extranodal NK/T-cell lymphoma, nasal type (ENKL) by skin biopsy. Because the lesion was localized on the subcutaneous tissue of the sole, she was treated with RT/2/3DeVIC, resulting in a complete response (CR). In March of the following year, PET/CT showed significant uptake and mucosal thickening in the right nasal cavity, and a mucosal biopsy confirmed ENKL infiltration. Because the lesion was localized in the nasal cavity, she was re-treated with RT/2/3DeVIC, with a focus on local control, and she achieved a second CR. She subsequently received allogeneic hematopoietic stem cell transplantation in the hope of preventing systemic relapse. She has remained in CR for four years since the transplantation. Our case suggests that allogeneic hematopoietic stem cell transplantation to be a potentially promising approach to curative treatment for recurrent ENKL in younger patients. As nasal lesions may subsequently appear during the course of primary non-nasal ENKL, ongoing meticulous evaluation for nasal lesions is important.


Asunto(s)
Pie/patología , Linfoma Extranodal de Células NK-T/patología , Cavidad Nasal/patología , Neoplasias Nasales/patología , Neoplasias Nasales/secundario , Neoplasias Cutáneas/patología , Adulto , Biopsia , Femenino , Humanos , Linfoma Extranodal de Células NK-T/terapia , Imagen Multimodal , Neoplasias Nasales/terapia , Tomografía de Emisión de Positrones , Recurrencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
6.
Cancer Sci ; 105(1): 97-104, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24206578

RESUMEN

Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia (APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all-trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count (P = 0.04), severe disseminated intravascular coagulation (P = 0.04), and coexpression of CD2 (P = 0.03), CD7 (P = 0.04), CD34 (P < 0.01) and/or human leukocyte antigen-DR (P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival (EFS) showed an inferior trend in CD56(+) APL (P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 10(9)/L or more, EFS and cumulative incidence of relapse in CD56(+) APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS (P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno CD56/biosíntesis , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antígeno CD56/genética , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/administración & dosificación , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recuento de Plaquetas , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Resultado del Tratamiento , Tretinoina/administración & dosificación , Adulto Joven
7.
Eur J Haematol ; 90(4): 331-9, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23360173

RESUMEN

OBJECTIVES: Invasive fungal diseases (IFDs) are life-threatening events in patients with haematologic disorders, and the spectrum of the aetiological pathogens continues to expand. This study aimed to evaluate the clinical utility of a panfungal polymerase chain reaction (PCR) assay for the management of IFDs in such patients. METHODS: We prospectively analysed 273 consecutive blood samples from 64 risk episodes in 51 patients with haematologic disorders at high risk for IFD who were treated at our hospital between April 2007 and October 2010. RESULTS: PCR-positive results were obtained in 18 of 64 risk episodes (35.3%). IFD was documented in 14 episodes (21.9%, 9 probable IFDs and 5 possible IFDs) according to the revised criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. PCR was positive in all of these 14 episodes, and in 4 of the 50 episodes with no IFD category. Sensitivity, specificity, positive predictive value, and negative predictive value of our assay were 100%, 92%, 78% and 100% respectively. A considerable number of fungi (44.4%) that are less common than Aspergillus and Candida species were positive by PCR. Molecular diagnoses of Cunninghamella species, Aspergillus ustus, Fusarium species, Scedosporium apiospermum, Rhodotorula species and Rhizopus species were beneficial in selecting suitable treatments. CONCLUSIONS: Our panfungal PCR approach allows for the highly sensitive and specific detection and identification of a wide spectrum of fungal pathogens, which provides indispensable information for managing IFDs, especially refractory or breakthrough IFDs during antifungal therapy in high-risk patients with haematologic disorders.


Asunto(s)
Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/microbiología , Micosis/diagnóstico , Micosis/etiología , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Secuencia de Bases , ADN de Hongos/genética , ADN de Hongos/aislamiento & purificación , Femenino , Fungemia/diagnóstico , Fungemia/etiología , Fungemia/microbiología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Micosis/microbiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Especificidad de la Especie , Adulto Joven
8.
Cancer Sci ; 103(11): 1974-8, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22834728

RESUMEN

Studies focused on elderly acute promyelocytic leukemia (APL) are relatively limited. To evaluate prognostic impact in elderly APL, we compared the long-term outcome of elderly APL patients (60-70 years) with younger patients (15-59 years) treated with all-trans retinoic acid combined with anthracycline and cytarabine in the Japan Adult Leukemia Study Group (JALSG) APL97 study. Of 283 evaluable patients, 46 (16.3%) were elderly who had more frequent lower platelet (P = 0.04), lower albumin (P = 0.006) and performance status 3 (P = 0.02), higher induction death rate due to differentiation syndrome (P = 0.03), and non-relapse mortality (NRM) during consolidation therapy (P = 0.001). Overall survival was significantly inferior in elderly patients (P = 0.005), but disease-free survival and cumulative incidence of relapse were not. Better therapeutic approaches should be considered to reduce NRM during induction and consolidation therapy in elderly APL. This study was registered at http://www.umin.ac.jp/ctrj/ under C000000206.


Asunto(s)
Leucemia Promielocítica Aguda/tratamiento farmacológico , Adulto , Anciano , Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Japón , Leucemia Promielocítica Aguda/patología , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Resultado del Tratamiento , Tretinoina/administración & dosificación
9.
J Clin Microbiol ; 48(6): 2030-6, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20392911

RESUMEN

This study aimed to assess the clinical utility of PCR for the analysis of bacteria and fungi from blood for the management of febrile neutropenic patients with hematologic malignancies. Using a PCR system able to detect a broad range of bacteria and fungi, we conducted a prospective pilot study of periodic analyses of blood from patients following intensive chemotherapy. When fever occurred, it was treated with empirical antibiotic therapy, basically without knowledge of the PCR results. In 23 febrile episodes during the neutropenic period, bacteria were detected by PCR in 11 cases, while the same species were identified by blood culture in 3 cases. In 10 out of 11 PCR-positive cases, fever could be managed by empirical therapy. In the empirical-therapy-resistant case, the identification of Stenotrophomonas maltophilia by PCR led to improvement of fever. No fungi were detected by PCR in febrile cases, while Aspergillus fumigatus was detected in one afebrile patient, several days before a clinical diagnosis was made. In subsequent sporadic PCR analyses in 15 cases of febrile neutropenia, bacteria were detected by both PCR and blood culture in 7 cases and by PCR alone in 6. Fungi were not detected. While fever was improved by empirical therapy in 12 out of the 13 PCR-positive cases, the identification of Pseudomonas aeruginosa by PCR in one therapy-resistant case contributed to the successful treatment of persistent fever. Our results indicate that PCR analysis of bacteria from blood provides essential information for managing empirical-therapy-resistant febrile neutropenia.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Sangre/microbiología , Fiebre de Origen Desconocido/etiología , Micosis/diagnóstico , Neutropenia/inmunología , Reacción en Cadena de la Polimerasa/métodos , Adulto , Anciano , Animales , Antibacterianos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Hongos/genética , Hongos/aislamiento & purificación , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Micosis/microbiología , Neutropenia/inducido químicamente , Resultado del Tratamiento , Adulto Joven
10.
J Exp Med ; 217(2)2020 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-31704808

RESUMEN

This report addresses whether small molecules can deplete FoxP3-expressing regulatory T (T reg) cells, thereby augmenting antitumor immunity. Imatinib, a tyrosine kinase inhibitor of oncogenic BCR-ABL protein expressed by chronic myelogenous leukemia (CML) cells, possesses off-targets including LCK expressed in T cells. We showed that imatinib-treated CML patients in complete molecular remission (CMR) exhibited selective depletion of effector T reg (eT reg) cells and significant increase in effector/memory CD8+ T cells while non-CMR patients did not. Imatinib at CML-therapeutic concentrations indeed induced apoptosis specifically in eT reg cells and expanded tumor antigen-specific CD8+ T cells in vitro in healthy individuals and melanoma patients, and suppressed colon tumor growth in vivo in mice. Mechanistically, because of FoxP3-dependent much lower expression of LCK and ZAP-70 in T reg cells compared with other T cells, imatinib inhibition of LCK further reduced their TCR signal intensity, rendering them selectively susceptible to signal-deprived apoptotis. Taken together, eT reg cell depletion by imatinib is instrumental in evoking effective immune responses to various cancers.


Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Mesilato de Imatinib/uso terapéutico , Inmunidad/efectos de los fármacos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Linfocitos T Reguladores/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Modelos Animales de Enfermedad , Femenino , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Humanos , Mesilato de Imatinib/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/antagonistas & inhibidores , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Ratones Transgénicos , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Linfocitos T Reguladores/inmunología , Resultado del Tratamiento
11.
Ann Hematol ; 88(6): 581-8, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19030858

RESUMEN

Increasing recipient age is a well-known risk factor for graft-versus-host disease (GVHD) and treatment-related mortality (TRM) and has a negative impact on allogeneic hematopoietic stem cell transplantation. Since the incidence of severe GVHD after cord blood transplantation (CBT) is lower than that after transplants using bone marrow or mobilized peripheral blood grafts from adult cells, we should expect better outcomes from CBT in older patients. To evaluate the feasibility and efficacy of myeloablative unrelated CBT in patients aged between 50 and 55 years, we performed a retrospective comparison of 100 patients with acute leukemia who received cord blood grafts at our institution. Nineteen older patients (median age, 52; range, 50-55) and 81 younger patients (median, 36; range, 16-49) received a myeloablative conditioning regimen including 12 Gy of total body irradiation and chemotherapy. GVHD prophylaxis included cyclosporine with (n = 96) or without (n = 4) methotrexate. There were no significant differences in the incidences of grades II to IV acute GVHD, extensive-type chronic GVHD, TRM, and the probability of overall and disease-free survival between these groups. These results suggest that, in patients with acute leukemia, myeloablative CBT might be as safe and effective in patients aged between 50 and 55 years as in younger patients.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Leucemia , Enfermedad Aguda , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped , Células Precursoras de Granulocitos , Humanos , Leucemia/patología , Leucemia/cirugía , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
12.
Rinsho Ketsueki ; 50(1): 44-8, 2009 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-19225229

RESUMEN

A 49-year-old woman with high fever and diffuse swelling of the right cheek was referred to our hospital. Computed tomography showed right orbital tumor with massive involvement. Histopathologic examination of the biopsied right orbital tumor demonstrated extranodal NK/T-cell lymphoma, nasal-type. She was treated with six courses of chemotherapy consisting of etoposide and dexamethasone with 50 Gy of concurrent involved-field radiotherapy. Facial swelling and liver dysfunction improved immediately, and after five courses of chemotherapy, she achieved partial remission without any severe adverse events. L-asparaginase was administered in the final course of chemotherapy. There is no evidence of recurrence 56 months after diagnosis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hepatopatías/complicaciones , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/radioterapia , Neoplasias Nasales/tratamiento farmacológico , Neoplasias Nasales/radioterapia , Neoplasias Orbitales/tratamiento farmacológico , Neoplasias Orbitales/radioterapia , Asparaginasa/administración & dosificación , Terapia Combinada , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma Extranodal de Células NK-T/complicaciones , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Nasales/complicaciones , Neoplasias Nasales/patología , Neoplasias Orbitales/complicaciones , Neoplasias Orbitales/patología , Dosificación Radioterapéutica , Inducción de Remisión , Factores de Tiempo , Resultado del Tratamiento
13.
Nihon Rinsho ; 67(10): 1969-73, 2009 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-19860199

RESUMEN

The management of microbial infection is one of the important issues for patients with acute myeloid leukemia (AML). They are considered to be at high risk for infection. They should be provided appropriate antimicrobial agents recommended by the Infectious Diseases Society of America (IDSA). Recently, there have been several significant changes in IDSA guidelines especially in the treatment of invasive fungal infection because of developments in several antifungal agents. This document constitutes the recommendations for the management of infection in patients with AML according to the updated guidelines of the IDSA. Evidence about infection control in AML is not enough in contrast to hematopoietic stem cell transplantation. Further studies are necessary to establish the strategy for microbial infections in AML.


Asunto(s)
Antibacterianos/administración & dosificación , Antifúngicos/administración & dosificación , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Leucemia Mieloide/complicaciones , Micosis/complicaciones , Micosis/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , Diagnóstico Diferencial , Fiebre/complicaciones , Fiebre/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Micosis/diagnóstico , Micosis/prevención & control , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Premedicación
14.
Biol Blood Marrow Transplant ; 14(12): 1341-7, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19041055

RESUMEN

We analyzed the disease-specific outcomes of adult acute myelogenous leukemia (AML) patients treated with unrelated cord blood transplantation (CBT) after myeloablative conditioning. Between August 1998 and February 2008, 77 adult patients with AML were treated with unrelated CBT. All patients received 4 fractionated 12 Gy total body irradiation (TBI) and chemotherapy as myeloablative conditioning. The median age was 45 years, the median weight was 55 kg, the median number of nucleated cells was 2.44 x 10(7)/kg, and the median number of CD34-positive cells was 1.00 x 10(5)/kg. All patients received a single and HLA mismatched cord blood unit. The cumulative incidence of neutrophil recovery at day 50 and platelet recovery at day 200 was 94.8% and 91.7%, respectively. A higher CD34-positive cell dose was associated with faster hematopoietic recovery. The cumulative incidence of grade III to IV acute graft-versus-host disease (aGVHD) and extensive-type chronic GVHD (cGVHD) was 25.1% and 28.6%, respectively. With a median follow-up of 78 months, the probability of event-free survival (EFS) at 5 years was 62.8%. The 5-year cumulative incidence of treatment related-mortality (TRM) and relapse was 9.7%, 25.8%, respectively. In multivariate analyses, the risk factor identified for event free survival (EFS) was disease status and cytogenetics. These results suggest that unrelated CBT after myeloablative conditioning could be safely and effectively used for adult patients with AML.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Antígenos HLA , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante , Enfermedad Aguda , Adolescente , Adulto , Anciano , Antígenos CD34 , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Incidencia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/fisiopatología , Masculino , Persona de Mediana Edad , Neutrófilos , Recuperación de la Función , Tasa de Supervivencia , Trasplante Homólogo
15.
Int J Hematol ; 87(1): 78-82, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18224418

RESUMEN

We encountered a case of acute myeloblastic leukemia (AML), with extramedullary leukemia (EML) and a masked type of the variant translocation t(8;21)(q22;q22). Morphologically, the AML M2 subtype according to the French-American-British (FAB) classification was present. Phenotypically, leukemic cells were negative for CD19 and positive for CD56. Clinically, the case showed chemo-refractoriness and a poor outcome. The initial karyotypic interpretation was t(8;9)(q22;q34) on G-banding. Multiplex-fluorescence in situ hybridization (multiplex-FISH) analysis revealed a three-way translocation involving chromosomes 8, 9, and 21, and identified a masked type of variant t(8;21)q22;q22) translocation. The karyotype was finally determined as 45,X,-Y,der(8)t(8;21)(q22;q22), der(9)(8;9)(q22;q34), and der(21)t(9;21)(q34;q22). Results of FISH using the AML1/ETO probe and detection of the AML1/ETO fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) support the karyotype as well as the sequence of the PCR product. Additionally, C-KIT mutation was detected.


Asunto(s)
Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 9/genética , Leucemia Mieloide Aguda/genética , Translocación Genética , Adulto , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Proteínas de Unión al ADN/genética , Hematopoyesis Extramedular/genética , Humanos , Masculino , Proteínas Proto-Oncogénicas/genética , Proteína 1 Compañera de Translocación de RUNX1 , Factores de Transcripción/genética
16.
Leuk Res ; 31(4): 471-6, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17052753

RESUMEN

The cytogenetic findings in acute myeloid leukemia (AML) are a powerful prognostic indicator. Among these abnormalities, the World Health Organization has classified inv(16)(p13q22), which is closely associated with the M4E classification in the French-American-British system, as indicating a good-risk AML. However, this chromosomal abnormality can often be difficult to detect. In this study, we used RT-PCR and FISH analysis to examine 224 Japanese adult de novo AML patients for the presence of the CBFB/MYH11 fusion transcript at the time of diagnosis. The CBFB/MYH11 fusion gene was detected in 17 patients (7.6%): eight patients had the inv(16) chromosome and in all of them it was M4E; nine patients did not have abnormalities in chromosome 16. AML with the CBFB/MYH11 fusion gene but without inv(16) was found in M2, M4, and M5, but not in M4E patients. There were no statistically significant differences in the clinical features of patients with the inv(16) and those with the cryptic inv(16) chromosome. These results indicate that even if eosinophilia is not found, molecular screening for CBFB/MYH11 fusion gene should be performed in all AML patients at the time of diagnosis to help guide disease management.


Asunto(s)
Leucemia Mieloide/genética , Proteínas de Fusión Oncogénica/genética , Enfermedad Aguda , Adulto , Inversión Cromosómica/genética , Cromosomas Humanos Par 16 , Humanos , Hibridación Fluorescente in Situ , Incidencia , Japón , Leucemia Mieloide/clasificación , Leucemia Mieloide/diagnóstico , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Int J Oncol ; 30(3): 549-55, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17273755

RESUMEN

Receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) share a common beta subunit. We recently reported that GM-CSF acts in concert with transforming growth factor-beta1 (TGF-beta1) and Notch ligand Delta-1 (Delta-1) to promote the differentiation of human blood monocytes into Langerhans cells. In the present study, we examined whether IL-3, in place of GM-CSF, can induce the development of Langerhans cells from blood monocytes in the presence of TGF-beta1 and Delta-1, because the IL-3 receptor alpha chain was substantially expressed on monocytes. However, the generation of Langerhans cells was not obtained by the combination of IL-3, TGF-beta1 and Delta-1, even though GM-CSF and IL-3 exhibited a similar effect with respect to the differentiation of monocytes into macrophages and dendritic cells. The addition of GM-CSF to the culture supplemented with IL-3, TGF-beta1 and Delta-1 restored the differentiation of monocytes toward Langerhans cells. A microarray analysis revealed that a number of genes including Langerhans cell markers, E-cadherin and Langerin, were specifically expressed in cells from GM-CSF-containing cultures but not in those from IL-3-containing cultures. These data suggest that IL-3 can not replace GM-CSF to induce the differentiation of human monocytes into Langerhans cells in culture.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Interleucina-3/fisiología , Células de Langerhans/citología , Monocitos/metabolismo , Cadherinas/metabolismo , Diferenciación Celular , Citometría de Flujo , Regulación de la Expresión Génica , Humanos , Interleucina-3/metabolismo , Receptores de Lipopolisacáridos/biosíntesis , Monocitos/citología , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Factor de Crecimiento Transformador beta1/metabolismo
18.
Intern Med ; 56(6): 707-711, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28321075

RESUMEN

Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.


Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Cunninghamella , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Mucormicosis/tratamiento farmacológico , Adulto , Anciano , Femenino , Neoplasias Hematológicas/complicaciones , Humanos , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Masculino , Persona de Mediana Edad , Mucormicosis/complicaciones , Mucormicosis/diagnóstico , Reacción en Cadena de la Polimerasa
19.
Leuk Res ; 30(10): 1235-9, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16533529

RESUMEN

The progenitor cells of myelodysplastic syndrome (MDS) are thought to undergo a multistep process during their transformation into overt acute leukemia. In this study, the role of mutation of the KIT gene in the extracellular membrane, juxtamembrane and tyrosine kinase domains was investigated in 75 patients with MDS or MDS-derived leukemia (MDS-AML). Mutation was detected in 2 of 15 (13.3%) patients with refractory anemia with excess blasts transformation (RAEB-T), in 1 of 15 (6.6%) patients with chronic myelomonocytic leukemia (CMML), and in 5 of 26 (19.2%) patients with MDS-AML. However, no mutation was found in any of the nine patients with refractory anemia (RA) or the 10 patients with refractory anemia with excess blasts (RAEB). Of the mutations, five patients had changes at the same codon in tyrosine kinase domain, Asp816, while the remainder had unique mutations. These observations suggest that KIT gene mutations identified in the advanced stage of MDS, and genetic abnormality in the KIT gene, particularly at codon 816, might be additional events that contribute to the progression of MDS to AML.


Asunto(s)
Médula Ósea/patología , Leucemia/genética , Mutación , Síndromes Mielodisplásicos/genética , Proteínas Proto-Oncogénicas c-kit/genética , Adulto , Anciano , Anemia Refractaria con Exceso de Blastos/genética , Codón/genética , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Humanos , Japón , Cariotipificación , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/fisiopatología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Leuk Res ; 30(8): 1053-7, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16504290

RESUMEN

Granulocytic sarcoma (GS) is a rare extra-medullary tumor and usually involves the skin, soft tissue, and lymph nodes. GS is found in 8% of acute myeloid leukemia (AML) patients, especially patients with t(8;21)AML. It has been suggested that GS is a poor prognostic factor in t(8;21)AML. Compared to t(8;21)AML, GS is rare in cases of inv(16)AML. Thus, the characteristics of inv(16) with GS are not well understood. Here, we describe a patient with AML and mesentery GS. The chromosomal analysis was normal, but molecular analysis detected the CBFB/MYH11 fusion gene in the blasts. A complete remission was achieved with standard induction therapy followed by high-dose cytarabine consolidation. We have also summarized 12 reported cases of inv(16)AML with GS and found that GS was commonly found in abdominal lesions. These observations suggest that when abdominal GS is diagnosed, an analysis of the CBFB/MYH11 fusion gene is necessary to make an appropriate decision regarding treatment options, even if no chromosomal abnormalities are found.


Asunto(s)
Cromosomas Humanos Par 16/genética , Leucemia Mieloide/genética , Mesenterio/patología , Proteínas de Fusión Oncogénica/genética , Sarcoma Mieloide/genética , Enfermedad Aguda , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Humanos , Hibridación Fluorescente in Situ/métodos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/tratamiento farmacológico , Masculino , Proteínas de Fusión Oncogénica/análisis , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/tratamiento farmacológico , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
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