RESUMEN
Microbial rhodopsins are the most widely distributed photoreceptors that bind a retinal Schiff base chromophore. Among them, a light-driven Cl- pump discovered from Mastigocladopsis repens (MrHR) is distinctive in that it has the structural features of both H+ and Cl- pumps. While the photocycle has been characterized by light-induced changes of the absorption spectrum, the structural changes of the retinal chromophore remain largely unknown. In this study, we examined the chromophore structural changes of MrHR by using cryogenic Raman spectroscopy. We observed five photointermediatesâK, L, N1, N2, and MrHR'âthat show distinct vibrational spectra, indicating atypical chromophore structures, e.g., small distortion in the K intermediate and Schiff base configurational change in the MrHR' intermediate. Based on the Raman spectra of two N intermediates (N1 and N2), we propose that N1 is the Cl--bound state and N2 is the Cl--unbound state, which are responsible for the Cl- release and uptake, respectively, to achieve Cl- pumping.
Asunto(s)
Luz , Espectrometría Raman , Procesos Fotoquímicos , Cloruros/química , Cloruros/metabolismoRESUMEN
Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 40% of all malignant lymphomas, making it the most common subtype. Molecular genetic studies have elucidated the pathogenesis of DLBCL and the causes of its poor prognosis. This basic research has led to the development of novel molecularly targeted therapies that target molecules and cellular antigens in relevant signaling pathways or epigenetic enzymes. Treatment with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone has become the standard of care for newly diagnosed CD20-positive DLBCL with an International Prognostic Index score of 2 to 5, based on its reported efficacy for this indication. In addition, the development of immunotherapy such as anti-CD19-chimeric antigen receptor (CAR)-T therapy and bispecific antibodies such as epcoritamab, mosunetuzumab, and glofitamab has led to a paradigm shift in treatment of relapsed/refractory DLBCL. This review summarizes the evolution of treatment development for DLBCL, as well as the results of the current clinical standard of care and new therapies that are expected to become the standard of care.
Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inmunoterapia/métodos , Terapia Molecular Dirigida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and safety of alemtuzumab in nine Japanese patients with T-PLL at five participating institutions who were treated between January 2015 and August 2023. The median age at first administration of alemtuzumab was 72 years (range, 39 to 78). Two patients were treatment naïve, and seven had been treated with a median of one (range, 1 to 3) prior systemic therapy. Six patients were refractory to their most recent therapy. Three patients completed 12 weeks of treatment. The overall response rate and the complete response (CR) rate were 78% and 11%, respectively. Among the six patients who achieved a partial response, two achieved clinical CR but did not undergo bone marrow examination. One patient also achieved clinical CR but did not undergo CT and bone marrow examination for response evaluation. The median progression-free survival time was 8.1 months (95% confidence interval, 0.9 to 18.6). Three patients received readministration of alemtuzumab monotherapy after disease progression. There were no treatment-related deaths. The grade 3 or 4 nonhematologic adverse events included infusion reaction (grade 3, n = 2), cytomegalovirus reactivation (grade 3, n = 2), and pulmonary edema (grade 3, n = 1). One patient experienced EpsteinâBarr virus-positive diffuse large B-cell lymphoma 15 months after the last dose of alemtuzumab. These results confirm that the efficacy and safety of alemtuzumab monotherapy in Japanese patients are comparable to those previously reported.
Asunto(s)
Alemtuzumab , Leucemia Prolinfocítica de Células T , Humanos , Alemtuzumab/uso terapéutico , Alemtuzumab/administración & dosificación , Alemtuzumab/efectos adversos , Leucemia Prolinfocítica de Células T/tratamiento farmacológico , Leucemia Prolinfocítica de Células T/mortalidad , Anciano , Persona de Mediana Edad , Masculino , Femenino , Japón , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversosRESUMEN
This single-arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)-guided therapy for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). Patients aged 16-60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five-point Deauville scale. PET2-negative patients continued an additional four cycles of ABVD, whereas PET2-positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co-primary endpoints were 2-year progression-free survival (PFS) among all eligible and PET2-positive patients. Ninety-three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28-48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2-positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2-negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow-up period of 41.1 months, the 2-year PFS of 92 eligible patients and 19 PET2-positive patients were 84.8% (80% confidence interval [CI], 79.2-88.9) and 84.2% (80% CI, 69.7-92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET-guided therapy is a useful treatment option for younger patients with newly diagnosed advanced-stage cHL. Registration number: jRCTs031180218.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Ciclofosfamida , Dacarbazina , Doxorrubicina , Etopósido , Enfermedad de Hodgkin , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Prednisona , Procarbazina , Vinblastina , Vincristina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Adulto , Dacarbazina/administración & dosificación , Dacarbazina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Persona de Mediana Edad , Procarbazina/administración & dosificación , Procarbazina/uso terapéutico , Femenino , Masculino , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Adulto Joven , Tomografía de Emisión de Positrones/métodos , Adolescente , Supervivencia sin ProgresiónRESUMEN
Secondary central nervous system involvement (sCNSi) in diffuse large B-cell lymphoma (DLBCL) is fatal. However, its features in patients with sCNSi who are categorized as lower risk by international prognostic index (IPI) or CNS-IPI are not yet fully understood. In the present analysis, we evaluated DLBCL patients who developed sCNSi at their first progression and who participated in JCOG0601, most of whom were lower risk by IPI. Of 409 patients, 21 (5.1%) developed sCNSi during a median follow-up of 4.9 years. Five-year cumulative incidence of sCNSi were 5.1%; and 4.0%, 5.3%, and 11.5% at low, intermediate, and high risk of CNS-IPI, respectively. The most common locations of extranodal lesions at the time of registration in patients with sCNSi were the stomach (n = 4), paranasal cavity (n = 3), and bone marrow (n = 2). In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval 1.28-14.73]). Median overall survival after sCNSi was 1.3 years, with a 2-year overall survival rate of 39.3%. The incidence of sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but paranasal cavity lesion might indicate high risk for organ involvement. CLINICAL TRIAL REGISTRATION: JCOG0601 was registered in the UMIN Clinical Trials Registry (UMIN000000929, date of registration; December 04, 2007) and the Japan Registry of Clinical Trials (jRCTs031180139, date of registration; February 20, 2019).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Nervioso Central , Ciclofosfamida , Doxorrubicina , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/epidemiología , Rituximab/uso terapéutico , Masculino , Femenino , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Doxorrubicina/uso terapéutico , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Adulto , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Anciano de 80 o más Años , Estudios de Seguimiento , Tasa de SupervivenciaRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a currative treatment modality for diffuse large B-cell lymphoma (DLBCL) because of the intrinsic graft-versus-lymphoma effect. However, limited information is available regarding which patients with relapsed or refractory DLBCL are likely to benefit from allo-HSCT. We retrospectively analyzed data from 1268 DLBCL patients who received allo-HSCT. The overall survival and progression-free survival (PFS) rates were 30.3% and 21.6% at 3 years, respectively. Multivariate analysis revealed that stable or progressive disease at transplantation, male patient, poorer performance status at transplantation, and shorter intervals from previous transplantation were associated independently with a lower PFS. Four prognostic factors were used to construct a prognostic index for PFS, predicting 3-year PFS of 55.4%, 43.7%, 20.4% and 6.6%, respectively. The prognostic model predicted relapse rates following allo-HSCT accordingly (P < 0.0001), whereas did not predict transplantation-related mortality (P = 0.249). The prognostic index can identify a subgroup of DLBCL patients who benefit from allo-HSCT and it is worthwhile to evaluate whether this model is also applicable to patients undergoing allo-HSCT in cases of relapse after chimeric antigen receptor engineered T-cell therapy, although the application of allo-HSCT has been declining with the increase of novel immunotherapies.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Masculino , Estudios Retrospectivos , Recurrencia Local de Neoplasia/terapia , Linfoma de Células B Grandes Difuso/terapia , RecurrenciaRESUMEN
Rituximab treatment significantly improved the outcomes of diffuse large B-cell lymphoma (DLBCL). A central nervous system (CNS) relapse remains a serious and fatal event for patients with DLBCL; therefore, the clinical question of the optimal treatment regimen for reducing the risk of CNS relapse remains unknown. The CNS-International Prognostic Index was identified as a predictive model for CNS relapse. No factors can completely predict CNS relapse although several reports regarding high-risk factors for CNS relapse have been reported. In practice, intrathecal methotrexate (MTX) and high-dose MTX therapy have been used for CNS prophylaxis. Unfortunately, evidence of the optimal therapy for CNS prophylaxis in patients with DLBCL remains lacking. This study aimed to review CNS relapse assessment and discuss study results with clinical impacts on CNS prophylaxis treatment strategies in DLBCL.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Humanos , Ciclofosfamida/uso terapéutico , Prednisona/uso terapéutico , Vincristina/uso terapéutico , Doxorrubicina/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/prevención & control , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Rituximab/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Metotrexato/uso terapéutico , Medición de Riesgo , Enfermedad Crónica , Sistema Nervioso CentralRESUMEN
Progression-free survival after R-High CHOP/CHASER/LEED with auto-PBSCT in untreated mantle cell lymphoma in JCOG0406 study. A continuous pattern of relapse was observed.
Asunto(s)
Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/diagnóstico por imagen , Linfoma de Células del Manto/tratamiento farmacológico , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia , Rituximab/uso terapéutico , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Prednisona/uso terapéuticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Humanos , Estudios de Seguimiento , Rituximab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , Etopósido/uso terapéutico , Doxorrubicina/uso terapéutico , Prednisona/efectos adversos , Vincristina/efectos adversos , Linfoma de Células B Grandes Difuso/tratamiento farmacológicoRESUMEN
Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare cutaneous T cell lymphoma that has been reported to be associated with autoimmune disorders but is most commonly associated with systemic lupus erythematosus. We herein report a 26-year-old man thought to have lupus panniculitis (LP) treated for 10 years with corticosteroids and cyclosporine. After several relapses with panniculitis, he was finally diagnosed with SPTCL, which was confirmed to have a HAVCR2 mutation for p.Tyr82Cys. We emphasize that rheumatologists should be aware of the possibility of SPTCL, despite its rare appearance, when making a diagnosis of LP or when encountering clinical manifestations that are not consistent with LP.
Asunto(s)
Linfoma de Células T , Paniculitis de Lupus Eritematoso , Paniculitis , Neoplasias Cutáneas , Masculino , Humanos , Adulto , Paniculitis de Lupus Eritematoso/diagnóstico , Paniculitis de Lupus Eritematoso/patología , Glucocorticoides/uso terapéutico , Ciclosporina/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico , Paniculitis/tratamiento farmacológico , Paniculitis/genética , Paniculitis/diagnóstico , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/genética , Diagnóstico Diferencial , Neoplasias Cutáneas/diagnóstico , Mutación , Receptor 2 Celular del Virus de la Hepatitis ARESUMEN
Histiocytic sarcoma (HS) is a rare malignancy showing morphologic and immunophenotypic features of histiocytes. HS has morphologic overlap with many other diseases, including various kinds of lymphomas. Gray zone lymphoma (GZL) is a rare B-cell lymphoma subtype characterized by overlapping features between diffuse large B-cell lymphoma and classic Hodgkin lymphoma. The histologic overlap with other diverse diseases of HS and the pathological diversity of GZL make it difficult to render a diagnosis. A 44-year-old woman who was initially diagnosed with HS was diagnosed with GZL after reexamination, including a genetic alteration test. After 6 cycles of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine, she achieved a complete response. Genomic alteration assessment may be useful for the accurate diagnosis of malignant lymphomas, which are difficult to diagnose, such as GZL.
Asunto(s)
Enfermedad de Hodgkin , Linfoma de Células B Grandes Difuso , Femenino , Humanos , Adulto , Enfermedad de Hodgkin/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Doxorrubicina/uso terapéutico , Dacarbazina/uso terapéutico , Genómica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Humanos , Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Prednisolona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
B-cell lymphoma accounts for approximately 70% of malignant lymphomas, and its treatment outcomes have drastically improved after the introduction of rituximab. Most patients with diffuse large B-cell lymphoma (DLBCL) are successfully treated with the current standard chemotherapeutic regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, 30-40% of patients with DLBCL have unsatisfactory treatment outcomes. Molecular genetic research has greatly contributed to the identification of pathogenic mechanisms of lymphoma and factors leading to poor prognosis. Thus, novel agents for targeting factors in key signaling pathways, relevant targeted antigens, and epigenetic enzymes have been developed. Additionally, development of immunotherapies such as anti-CD19-chimeric antigen receptor (CAR) T cell and bispecific antibody therapy have led to a paradigm shift for relapsed or refractory DLBCL treatments. Herein, we discuss the results of clinically impactful studies on the treatment strategies of B-cell lymphoma, including DLBCL, follicular lymphoma, and lymphoplasmacytic lymphoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
More than half of patients with malignant lymphoma are 65 years old or older. The outcome for older patients is poorer than that for younger patients. A poor prognosis is associated with heterogeneity and consists of physical function, performance status, poor nutritional status and various comorbidities. Therefore, attention should be given to serious treatment-related toxicities. Diffuse large B-cell lymphoma is the most frequently diagnosed type of malignant lymphoma. Most patients with diffuse large B-cell lymphoma can be potentially cured with the current standard chemotherapeutic regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. However, a reduced-dose regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or alternative treatment options might be suitable for older patients who are frail or unfit and have cardiac comorbidities. A comprehensive geriatric assessment is a potential tool for determining an appropriate therapeutic approach for each older patient. Follicular lymphoma is the second most common type of non-Hodgkin lymphoma, and the disease course is usually characterized by an indolent clinical course. Advanced follicular lymphoma with a high tumor burden has historically been treated with chemoimmunotherapy, but the treatment goal for older patients is relief of symptoms. Incorporating novel targeted agents such as brentuximab vedotin into therapies for older Hodgkin lymphoma patients might be a promising alternative to the anthracycline-containing regimen.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Linfoma de Células B Grandes Difuso , Anciano , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: There is currently no standard prognostic model optimized for the patients with diffuse large B-cell lymphoma (DLBCL) treated with upfront intensive immunochemotherapy including autologous stem cell transplantation (ASCT). The Kyoto Prognostic Index (KPI) has been proposed as a novel prognostic model for DLBCL, which can accurately identify especially high-risk patients. In this study, we investigated the prognostic value of the KPI in JCOG0908 trial in which higher-risk DLBCL patients defined by the conventional International Prognostic Index (IPI) were treated with upfront high dose therapy followed by ASCT. METHODS: Fifty-eight patients with DLBCL, not otherwise specified, enrolled in JCOG0908 and confirmed by the central pathological review were analyzed. The Kaplan-Meier method was used to estimate the probabilities of overall survival (OS) and progression-free survival (PFS). We compared the discrimination ability of the KPI with that of the IPI. RESULTS: According to KPI, 3-year OS and PFS rates were 86.7% and 76.7% in low-intermediate, 73.3% and 60.0% in high-intermediate, and 61.5% and 46.2% in high-risk group. According to IPI, 3-year OS and PFS rates were 75.0% and 50.0% in low-intermediate, 82.9% and 74.3% in high-intermediate, and 63.6% and 54.5% in high-risk group. The concordance-indices of KPI and IPI were 0.642 and 0.580 for OS and 0.606 and 0.606 for PFS. CONCLUSIONS: The KPI may be a suitable predictor of outcome than the IPI for patients with higher-risk DLBCL treated with upfront intensive immunochemotherapy including ASCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéutico , Trasplante AutólogoRESUMEN
To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.
Asunto(s)
Linfoma Extranodal de Células NK-T , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa , Carboplatino , Sistema Nervioso Central/patología , Dexametasona , Etopósido , Humanos , Ifosfamida , Células Asesinas Naturales/patología , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Metotrexato , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Bortezomib (Btz) shows robust efficacy in patients with multiple myeloma (MM); however, some patients experience suboptimal responses and show specific toxicities. Therefore, we attempted to identify specific HLA alleles associated with Btz-related toxicities and response to treatment. Eighty-two transplant-ineligible patients with newly diagnosed MM enrolled in a phase II study (JCOG1105) comparing two less intensive melphalan, prednisolone, plus Btz (MPB) regimens were subjected to HLA typing. The frequency of each allele was compared between the groups, categorized based on toxicity grades and responses to MPB therapy. Among 82 patients, the numbers of patients with severe peripheral neuropathy (PN; grade 2 or higher), skin disorders (SD; grade 2 or higher), and pneumonitis were 16 (19.5%), 15 (18.3%), and 6 (7.3%), respectively. Complete response was achieved in 10 (12.2%) patients. Although no significant HLA allele was identified by multiple comparisons, several candidates were identified. HLA-B*40:06 was more prevalent in patients with severe PN than in those with less severe PN (odds ratio [OR] = 6.76). HLA-B*40:06 and HLA-DRB1*12:01 were more prevalent in patients with SD than in those with less severe SD (OR = 7.47 and OR = 5.55, respectively). HLA-DRB1*08:02 clustered in the group of patients with pneumonitis (OR = 11.34). Complete response was achieved in patients carrying HLA-DQB1*03:02, HLA-DQB1*05:01, and HLA-DRB1*01:01 class II alleles. HLA genotyping could help predict Btz-induced toxicity and treatment efficacy in patients with MM, although this needs further validation.
Asunto(s)
Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Técnicas de Genotipaje/métodos , Antígenos HLA/genética , Melfalán/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Prednisolona/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Bortezomib/efectos adversos , Femenino , Frecuencia de los Genes , Humanos , Japón , Masculino , Melfalán/efectos adversos , Mieloma Múltiple/genética , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Neumonía/inducido químicamente , Neumonía/epidemiología , Prednisolona/efectos adversos , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/epidemiología , Resultado del TratamientoRESUMEN
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.
Asunto(s)
Neoplasias Encefálicas/patología , Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Intestinales/patología , Linfoma de Células T/patología , Recurrencia Local de Neoplasia/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/etiología , Femenino , Humanos , Neoplasias Intestinales/terapia , Linfoma de Células T/terapia , Recurrencia Local de Neoplasia/etiologíaRESUMEN
Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.