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1.
Int J Clin Oncol ; 27(1): 213-223, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34599413

RESUMEN

BACKGROUND: Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor T-cell based anti-CD19 therapy. The ZUMA-1 study, multicenter, single-arm, registrational Phase 1/2 study of axi-cel demonstrated high objective response rate in patients with relapsed/refractory large B-cell lymphoma. Here, we present the results of the bridging study to evaluate the efficacy and safety of axi-cel in Japanese patients (JapicCTI-183914). METHODS: This study was the phase 2, multicenter, open-label, single-arm trial. Following leukapheresis, axi-cel manufacturing and lymphodepleting chemotherapy, patients received a single infusion of axi-cel (2.0 × 106 cells/kg). Bridging therapy between leukapheresis and conditioning chemotherapy was not allowed. The primary endpoint was objective response rate. RESULTS: Among 17 enrolled patients, 16 received axi-cel infusion. In the 15 efficacy evaluable patients, objective response rate was 86.7% (95% confidence interval: 59.5-98.3%); complete response/partial response were observed in 4 (26.7%)/9 (60.0%) patients, respectively. No dose-limiting toxicities were observed. Grade ≥ 3 treatment-emergent adverse events occurred in 16 (100%) patients-most commonly neutropenia (81.3%), lymphopenia (81.3%) and thrombocytopenia (62.5%). Cytokine release syndrome occurred in 13 (81.3%) patients (12 cases of grade 1 or 2 and 1 case of grade 4). No neurologic events occurred. Two patients died due to disease progression, but no treatment-related death was observed by the data-cutoff date (October 23, 2019). CONCLUSION: The efficacy and safety of axi-cel was confirmed in Japanese patients with relapsed/refractory large B-cell lymphoma who have otherwise limited treatment options. TRIAL REGISTRATION: JapicCTI-183914.


Asunto(s)
Productos Biológicos , Linfoma de Células B Grandes Difuso , Antígenos CD19 , Humanos , Japón , Linfoma de Células B Grandes Difuso/tratamiento farmacológico
2.
Int J Clin Oncol ; 27(2): 265-280, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34973107

RESUMEN

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).


Asunto(s)
Preservación de la Fertilidad , Neoplasias , Oncólogos , Adolescente , Niño , Femenino , Humanos , Japón , Oncología Médica , Neoplasias/terapia , Adulto Joven
3.
Int J Clin Oncol ; 27(2): 281-300, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35022887

RESUMEN

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.


Asunto(s)
Preservación de la Fertilidad , Neoplasias , Oncólogos , Adolescente , Niño , Humanos , Japón , Oncología Médica , Neoplasias/terapia , Adulto Joven
4.
Ann Hematol ; 99(12): 2787-2800, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32879992

RESUMEN

Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005.


Asunto(s)
Diferenciación Celular/fisiología , Hemorragia/diagnóstico , Hemorragia/mortalidad , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/mortalidad , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Femenino , Hemorragia/tratamiento farmacológico , Humanos , Japón , Leucemia Promielocítica Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Valor Predictivo de las Pruebas , Estudios Prospectivos , Inducción de Remisión/métodos , Adulto Joven
5.
Ann Hematol ; 98(1): 83-91, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30251205

RESUMEN

We analyzed the clinical significance and genetic features of ASXL2 and ZBTB7A mutations, and the alternatively spliced isoform of the RUNX1-RUNX1T1 transcript, which is also called AML1-ETO9a (AE9a), in Japanese CBF-AML patients enrolled in the JALSG AML201 study. ASXL2 and ZBTB7A genes were sequenced using bone marrow samples of 41 AML patients with t(8;21) and 14 with inv(16). The relative expression levels of AE9a were quantified using the real-time PCR assay in 23 AML patients with t(8;21). We identified ASXL2 (34.1%) and ZBTB7A (9.8%) mutations in only AML patients with t(8;21). ASXL2-mutated patients had a significantly higher WBC count at diagnosis (P = 0.04) and a lower frequency of sex chromosome loss than wild-type patients (33 vs. 76%, respectively, P = 0.01). KIT mutations were the most frequently accompanied with both ASXL2 (36%) and ZBTB7A (75%) mutations. Neither ASXL2 nor ZBTB7A mutations had an impact on overall or event-free survival. Patients harboring cohesin complex gene mutations expressed significantly higher levels of AE9a than unmutated patients (P = 0.03). In conclusion, ASXL2 and ZBTB7A mutations were frequently identified in Japanese AML patients with t(8;21), but not in those with inv(16). Further analysis is required to clarify the detailed biological mechanism of AE9a regulation of the cohesin complex.


Asunto(s)
Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 8/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Proteínas de Unión al ADN , Regulación Leucémica de la Expresión Génica , Leucemia Mieloide Aguda , Proteínas de Fusión Oncogénica , Proteína 1 Compañera de Translocación de RUNX1 , Proteínas Represoras , Factores de Transcripción , Translocación Genética , Adolescente , Adulto , Anciano , Niño , Subunidad alfa 2 del Factor de Unión al Sitio Principal/biosíntesis , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/biosíntesis , Proteínas de Fusión Oncogénica/genética , Proteína 1 Compañera de Translocación de RUNX1/biosíntesis , Proteína 1 Compañera de Translocación de RUNX1/genética , Proteínas Represoras/biosíntesis , Proteínas Represoras/genética , Tasa de Supervivencia , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética
6.
Rinsho Ketsueki ; 60(2): 87-92, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-30842385

RESUMEN

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive type of non-Hodgkin lymphoma with a poor prognosis and no defined optimal therapeutic strategies. We retrospectively analyzed the survival of six PCNSL patients who were treated with high-dose methotrexate (HDMTX) -based chemotherapy combined with rituximab. The median age at diagnosis was 71 (range, 54-75) years, and the ECOG performance status was ≥3 in four patients. The histopathological findings revealed that all patients had diffuse large B-cell lymphoma. Objective response was obtained in all patients (five, complete response; one, partial response). Three patients had severe non-hematological toxicities: one had pulmonary thromboembolism, one had sepsis, and one developed acute epididymitis. However, each patient recovered and their symptoms could be managed. The median follow-up was 28.8 (range, 13.4-65.5) months. Five patients were still alive and disease-free, and one patient relapsed 62.2 months after the diagnosis. Therefore, the addition of rituximab to HDMTX may improve outcomes. Further clinical investigation is necessary to establish standardized initial therapies for PCNSL, particularly in elderly patients.


Asunto(s)
Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/uso terapéutico , Rituximab/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
7.
Ann Hematol ; 97(1): 73-81, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29196987

RESUMEN

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5-25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.


Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Delgadez/complicaciones , Delgadez/mortalidad , Adolescente , Adulto , Índice de Masa Corporal , Peso Corporal/fisiología , Femenino , Humanos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
8.
Rinsho Ketsueki ; 59(6): 669-674, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-29973441

RESUMEN

The JAK2V617F mutation is the commonest major genetic mutation of myeloproliferative neoplasms (MPNs) and has been defined in the WHO diagnostic criteria for MPNs. However, there is still no approved in vitro diagnostic test kit available in Japan. We evaluated a JAK2V617F allele quantification kit (test method) in a prospective, multicenter clinical performance study involving patients with MPNs who were diagnosed with polycythemia vera, essential thrombocythemia, and primary myelofibrosis; healthy volunteers were also included in the analysis. Good correlation was observed between the allele burden determined using the test method vs. that determined using next-generation sequencing (NGS) in the patient group (r=0.998, y=1.071x-0.069; n=156). Furthermore, all allele burdens in the healthy group (n=54) were below the lower limit of the measurement range of the test method (0.042%). Our results confirmed that the test method could quantitatively measure the JAK2V617F allele burden in patients with MPN. Thus, the novel JAK2V617F allele quantification kit can be considered useful for the diagnosis of MPNs.


Asunto(s)
Pruebas Genéticas/instrumentación , Janus Quinasa 2/genética , Trastornos Mieloproliferativos/genética , Policitemia Vera/genética , Estudios de Casos y Controles , Humanos , Japón , Mutación , Estudios Prospectivos
10.
Rinsho Ketsueki ; 58(6): 601-606, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-28679989

RESUMEN

Myelodysplastic syndrome with myelofibrosis (MDS-F) is a disease with a poor prognosis, and patients with this condition are at an increased risk of engraftment failures after allogeneic hematopoietic stem cell transplantation (SCT). Azacitidine (AZA) is effective in high-risk MDS patients. However, the effects of AZA on MDS-F have not been elucidated. AZA was administered to a 62-year-old male with MDS-F for 7 days at a dose of 75 mg/m2. Hematological improvements were observed after only 1 course of treatment. No suitable donor was found through the Japan Marrow Donor Program; therefore, the patient underwent umbilical cord blood transplant (UCBT). Neutrophil engraftment was observed on day 21 after the transplant procedure. He developed acute graft versus host disease (GVHD) of the skin (stage 3/grade II), but it could be controlled using prednisolone. Chronic GVHD was not observed and he was discharged in good general condition on day 68. While treatment prior to allogeneic SCT of MDS-F has not been established, in the present case, the hematological improvement brought about by AZA likely contributed to the patient's positive response to UCBT.


Asunto(s)
Azacitidina/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical , Síndromes Mielodisplásicos/terapia , Mielofibrosis Primaria/terapia , Sangre Fetal , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Mielofibrosis Primaria/complicaciones , Trasplante Homólogo
11.
Br J Haematol ; 174(4): 563-70, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27072050

RESUMEN

Pegfilgrastim is a pegylated form of the granulocyte-colony stimulating factor, filgrastim. Herein, we report the results of a multicentre, randomized, double-blind phase III trial comparing the efficacy and safety of pegfilgrastim with filgrastim in patients with malignant lymphoma. Patients were randomized to receive either a single subcutaneous dose of pegfilgrastim or daily subcutaneous doses of filgrastim on day 4 after the completion of cyclophosphamide, cytarabine, etoposide and dexamethasone ± rituximab (CHASE(R); day 1-3) chemotherapy. The primary endpoint was the duration of severe neutropenia (DSN), defined as the number of days with neutrophil count <0·5 × 10(9) /l in the first cycle of chemotherapy. A total of 111 lymphoma patients were randomized to either the pegfilgrastim or filgrastim group. 109 patients received either pegfilgrastim (n = 54) or filgrastim (n = 55). Efficacy data were available for 107 patients (pegfilgrastim: n = 53, filgrastim: n = 54). Both groups were well balanced in terms of gender, age, performance status and other variables. The mean DSN (±S.D.) was 4·5 (±1·2) and 4·7 (±1·3) d in the pegfilgrastim and filgrastim groups. No significant difference in safety was observed. This trial verified the non-inferiority of a single subcutaneous dose of pegfilgrastim compared with daily subcutaneous doses of filgrastim, considering DSN as an indicator.


Asunto(s)
Filgrastim/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Linfoma/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Citarabina/efectos adversos , Citarabina/uso terapéutico , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Manejo de la Enfermedad , Método Doble Ciego , Etopósido/efectos adversos , Etopósido/uso terapéutico , Femenino , Humanos , Linfoma/complicaciones , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Polietilenglicoles , Proteínas Recombinantes/administración & dosificación , Rituximab/efectos adversos , Rituximab/uso terapéutico , Adulto Joven
12.
Ann Hematol ; 94(3): 491-6, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25325985

RESUMEN

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Leucemia/terapia , Tacrolimus/administración & dosificación , Tacrolimus/farmacocinética , Adulto , Anciano , Preparaciones de Acción Retardada , Esquema de Medicación , Femenino , Humanos , Leucemia/metabolismo , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Donante no Emparentado , Adulto Joven
13.
Rinsho Ketsueki ; 56(10): 2267-76, 2015 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-26458468

RESUMEN

Granulocyte colony stimulating factor (G-CSF) plays important roles in treating hematologic malignancies including hematopoietic stem cell transplantation (HCT) and intensive chemotherapy. In the situation of peripheral blood cell transplantation (PBSCT), G-CSF mobilizes hematopoietic stem cells and progenitor cells into peripheral blood and thereby accelerates recovery from neutropenia and thus prevents serious infections after transplantation. In the setting of chemotherapy administration for leukemia and lymphoma, G-CSF can be given to prevent febrile neutropenia (FN) in order to maintain drug intensity and thus improve therapeutic outcomes. Based upon the guidelines abroad and in our country, G-CSF should be used as primary or secondary prophylaxis according to the risk of developing FN during chemotherapy. Patients with acute leukemia who received extremely high-risk chemotherapy benefitted from prophylactic treatment with G-CSF, especially those with acute lymphoblastic leukemia. In treating lymphomas for patients given a regimen with a high risk for FN (>20%), administration of G-CSF as primary prophylaxis is recommended. In addition, administration of primary prophylactic G-CSF is also recommended for patients given a regimen with an intermediate risk for FN (10-20%), if they have risk factors for worsening FN or infection.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neutropenia Febril/prevención & control , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Guías de Práctica Clínica como Asunto , Factores de Riesgo
14.
Rinsho Ketsueki ; 56(8): 1082-8, 2015 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-26345571

RESUMEN

Primary effusion lymphoma (PEL) is a large B-cell lymphoma proliferating only in the body cavity effusion. It often occurs in advanced AIDS patients and is associated with human herpesvirus 8 (HHV-8). On the other hand, HHV-8 negative effusion lymphoma, which is different from PEL in many ways, has also been reported and is referred to as HHV8-unrelated PEL-like lymphoma. This lymphoma is very rare and its clinical characteristics have not yet been fully clarified. We therefore report an HIV seronegative elderly patient with HHV8-unrelated PEL-like lymphoma. An 89-year-old woman was admitted to our hospital due to general fatigue and dyspnea. The patient presented with left pleural effusion in the absence of lymphadenopathy and tumor masses. The pathological examination of the pleural effusion showed proliferation of atypical large lymphoid cells, which were positive for CD19, CD20, CD10, CD38, CD7, BCL2 and BCL6 but negative for CD5, CD30, MUM1, surface immunoglobulin, HHV-8 and EBV. Cytogenetic analysis showed a complex karyotype including t(8;14)(q24;q32). The pleural effusion decreased in response to monotherapy with oral low-dose etoposide, but recurrence was detected 7 months later. Rituximab was transiently effective for the recurrent pleural effusion, but the patient died of lymphoma exacerbation 13 months after the diagnosis.


Asunto(s)
Cromosomas Humanos Par 14 , Cromosomas Humanos Par 8 , Linfoma de Efusión Primaria/genética , Anciano de 80 o más Años , Resultado Fatal , Femenino , Herpesvirus Humano 8 , Humanos , Linfoma de Efusión Primaria/diagnóstico por imagen , Radiografía
15.
Cancer Sci ; 105(11): 1435-41, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25181936

RESUMEN

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057-1.013; 80% CI, 0.093-0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αß T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.


Asunto(s)
Quimioradioterapia , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/terapia , Adulto , Anciano , Antígenos de Diferenciación de Linfocitos T/metabolismo , Biomarcadores/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación in Situ , Linfoma Extranodal de Células NK-T/mortalidad , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Recurrencia , Resultado del Tratamiento , Proteínas de la Matriz Viral/metabolismo
17.
Rinsho Ketsueki ; 55(5): 534-40, 2014 05.
Artículo en Japonés | MEDLINE | ID: mdl-24881918

RESUMEN

In a multicenter study, we evaluated the Major BCR-ABL mRNA/ABL mRNA quantification kit (M135R), which uses reference material included in the kit designed to report results using the international scale (IS). In total, 127 samples were studied. A good correlation was observed between M135R results and home-brew RT-qPCR results, which are reported on the IS using a conversion factor (r=0.90; n=115). However, the correlation coefficient between M135R results and Amp-CML results was relatively low (r=0.56; n=108). A good correlation was observed between M135R results from the two assay sites (r=0.94; n=115). The subset analysis of samples from the two assay sites showed M135R to have a good correlation even in the low IS range (r=0.98; IS≤1%). M135R showed high sensitivity and accuracy for detecting minimal residual disease and is considered to be a useful tool for treatment response assessment and for early detection of recurrence in CML patients.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , ARN Mensajero/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Calibración , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/tratamiento farmacológico , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Transducción de Señal/fisiología , Adulto Joven
18.
Gan To Kagaku Ryoho ; 41(6): 694-701, 2014 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-25129082

RESUMEN

There are two main types of therapy for hematologic malignancies: intensive cytotoxic chemotherapy and hematopoietic stem cell transplantation(HSCT). The roles of granulocyte colony-stimulating factor(G-CSF)in patients receiving HSCT are the mobilization of hematopoietic stem cells/progenitor cells into peripheral blood and the enhancement of neutrophil recovery as therapy or prophylaxis for fatal complications following HSCT. In the treatment of acute leukemias, G-CSF is used as therapy or prophylaxis for febrile complications during remission induction and post-remission therapies. In the treatment of lymphomas, primary prophylactic G-CSF is recommended during all cycles of chemotherapy when the expected incidence of neutropenic fever is more than 20% or when the patient is treated with potentially curative regimens. G-CSF is used as secondary prophylaxis to maintain dose intensity in patients with lymphomas treated in settings where reductions in chemotherapy dose intensity or dose density are associated with poorer prognosis. In the treatment of multiple myelomas, prophylactic G-CSF can be used when there is a high estimated risk of neutropenic fever(e. g., in patients receiving high-dose chemotherapy). For all cases, the appropriate use of G-CSF is recommended in accordance with the guidelines of the American Society of Clinical Oncology(ASCO), European Organisation for Research and Treatment of Cancer(EORTC), Infectious Diseases Society of America(IDSA), National Comprehensive Cancer Network(NCCN), and our JSCO-2013.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Trasplante de Células Madre Hematopoyéticas , Humanos , Neutropenia/prevención & control
20.
Nihon Rinsho ; 72(6): 1068-72, 2014 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-25016806

RESUMEN

More than 10 years have passed since imatinib as a first developed BCR-ABL tyrosine kinase inhibitor (TKI) introduced in treatment of patients with chronic myeloid leukemia (CML). In globally, there are tremendous numbers of patients on imatinib therapy. Based upon randomized trials comparing second generation TKIs such as dasatinib and nilotinib versus imatinib, both TKIs produce faster and deeper response than imatinib and they can be selected as first-line therapy for newly diagnosed chronic phase of CML (CP-CML) as imatinib. Bosutinib is a potent for imatinib resistant/intolerant CP-CML and can be used as second or third-line therapy. Ponatinib is the only clinically available TKI that has activity against the T315 mutation that is resistant to all other TKIs. Currently, a choice among these potent TKIs should take into consideration the drug side effect profiles and the patient's comorbidities.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Terapia Molecular Dirigida , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Compuestos de Anilina/uso terapéutico , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Humanos , Mesilato de Imatinib , Imidazoles/uso terapéutico , Nitrilos/uso terapéutico , Piperazinas/uso terapéutico , Piridazinas/uso terapéutico , Pirimidinas/uso terapéutico , Quinolinas/uso terapéutico
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