RESUMEN
Peptide-binding motif (PBM) model, a hierarchical clustering of HLA class I based on their binding specificity, was developed to predict immunopeptidome divergence. The effect of PBM mismatches on outcomes is unknown in HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo). We therefore conducted a retrospective study using national registry data in PTCy-haplo. Overall, 1352 patients were included in the study. PBM-A bidirectional mismatch was associated with an increased risk of overall mortality in multivariable analysis (hazard ratio, 1.26; 95% confidence interval, 1.06 to 1.50; p = 0.010). None of relapse, non-relapse mortality (NRM) and graft-versus-host disease showed significant differences according to PBM-A bidirectional mismatch status in the entire cohort. The impact of PBM-A bidirectional mismatch on overall survival (OS) was preserved within the HLA-A genotype bidirectional mismatch population, and their lower OS stemmed from higher relapse rate in this population. The worse OS due to high NRM with PBM-A bidirectional mismatch was prominent in lymphoid malignancies receiving reduced-intensity conditioning. The PBM model may predict outcomes more accurately than HLA genotype mismatches. In conclusion, this study demonstrated that the presence of PBM-A bidirectional mismatch elevated the risk of mortality of PTCy-haplo. Avoiding PBM-A bidirectional mismatch might achieve better outcomes in PTCy-haplo.
RESUMEN
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
Recently, allogeneic peripheral blood stem cell transplantation from human leukocyte antigen (HLA)-haploidentical donors using post-transplantation cyclophosphamide (PTCY-haploPBSCT) has become available in clinical practice. However, the efficacy of PTCY in adult T-cell leukemia (ATL) is not fully established yet. In this study, we retrospectively examined data of seven patients who underwent PTCY-haploPBSCT. The overall survival rate at 100 days after transplantation was 85.7%, and the 1-year overall survival rate was 68.6%. The cumulative incidence of relapse at 1 year was 31.4%, whereas the 1-year nonrelapse mortality was 17.1%. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) on day 100 was 14.3%, and the incidence of chronic GVHD at 1 year was 33.3%. These results suggest that PTCY-haploPBSCT can be a viable option even in patients with ATL. Further accumulation of knowledge and improvement of transplantation outcomes are warranted in the future.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Trasplante de Células Madre de Sangre Periférica , Adulto , Ciclofosfamida/uso terapéutico , Antígenos HLA , Humanos , Leucemia-Linfoma de Células T del Adulto/terapia , Estudios Retrospectivos , Acondicionamiento PretrasplanteRESUMEN
Discontinuation of tyrosine kinase inhibitors (TKIs) is now a feasible therapeutic goal for patients with chronic phase chronic myeloid leukemia (CML-CP). Whereas approximately half of patients experience molecular relapse, after resuming with any TKI; the majority re-achieve a deep molecular response (DMR). It is unclear whether such patients who re-achieve a durable DMR can discontinue TKI safely again. Here, we retrospectively assessed first, second, and third attempts to stop TKIs in patients with CML-CP. At the first attempt, 28 out of a total of 53 patients achieved sustained treatment-free remission (TFR; 53.4%; 95% confidence interval [CI], 39.0%-65.9%). Subsequently, 10 of 25 patients attempted a second TKI discontinuation, and in all cases, this was after receiving second-generation TKIs. Four of 10 patients successfully achieved TFR (37.5%; 95% CI, 9.9%-65.9%). All patients who relapsed at the second TKI discontinuation attempt were re-administered TKIs, and soon achieved at least a major molecular remission. All six second relapse patients had a loss of MR4.5 at 3 months after TKI discontinuation. These findings suggest that second and third attempts to successfully stop TKI treatment are feasible in patients with CML-CP.
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Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Humanos , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Novel anti-myeloma drugs have significantly improved the overall survival (OS) of patients with multiple myeloma (MM). However, not all MM patients treated with these drugs show survival benefits, and biologic and genetic prognostic factors are insufficient to predict the response to treatment. Decreasing treatment-related complications is important to improve the efficacy of treatment in patients with MM. The Controlling Nutritional Status (CONUT) score is a screening method for poor nutritional status, which is associated with poor prognosis in several cancers because it increases the rate of treatment-related complications. We retrospectively analyzed the OS of 64 patients with symptomatic MM and evaluated the correlation between the CONUT score and patient prognosis in MM. The median age at diagnosis was 66 years, and multivariate analysis showed that a high CONUT score (≥ 5; hazard ratio, 3.937; 95% confidence interval, 1.214-12.658; P = 0.022) was an independent prognostic risk factor. Subgroup analysis was performed according to patient age because the choice of treatment strategy, particularly autologous peripheral blood stem cell transplantation (auto-PBSCT), can vary depending on age in MM patients. Younger patients (< 65 years old) who received auto-PBSCT and had a lower CONUT score (0-3) showed a significantly better survival outcome than those with a higher CONUT score (≥ 4) (median OS, not reached vs. 64.1 months; P = 0.011). The CONUT score is simple to calculate and provides a useful prognostic indicator in patients with MM, especially transplant-eligible patients.
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Mieloma Múltiple , Estado Nutricional , Trasplante de Células Madre de Sangre Periférica , Adulto , Anciano , Anciano de 80 o más Años , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Mieloma Múltiple/fisiopatología , Mieloma Múltiple/terapia , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Membranous nephropathy (MN) is a common glomerular disease that is characterized by diffuse thickening of the glomerular basement membrane, and a common cause of nephrotic syndrome (NS). MN is often accompanied with malignant disease; The solid tumors are commonly associated with MN, whereas hematological malignancies are rarely found in patients with MN. A 68-year-old man with a history of diabetes mellitus visited a hospital with a chief complaint of general fatigue. He was previously not diagnosed with any complications of diabetes. Computed tomography revealed a pancreatic tumor, and the pathological findings of the biopsied tumor revealed the tumor was diffuse large B-cell lymphoma (DLBCL). Concurrently, he developed severe proteinuria, hypoalbuminemia, systemic edema and hyperlipidemia, consistent with the diagnosis of NS. The biopsied renal specimen revealed minute spike lesions of glomerular basement membrane, and abnormal lymphocytes infiltrated in the kidney interstitially. Anti-glomerular basement membrane antibody, proteinase-3-/myeloperoxidase antineutrophil cytoplasmic antibody and hepatitis B antigenemia, are absent in the patient. Serum anti-phospholipase A2 receptor (PLA2R) antibody (marker for primary MN) was not detected. A diagnosis of secondary MN induced by DLBCL was made. He received rituximab containing chemotherapy for DLBCL, resulting in amelioration of both DLBCL and MN. We report the rare case of a patient co-existing NS and DLBCL. DLBCL might be pathogenesis of NS; the findings are supported by the presence of MN, an underlying malignancy (DLBCL), and the lack of anti-PLA2R antibodies. Although further investigation is warranted, our case suggests that DLBCL is a possible cause of secondary MN.
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Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Síndrome Nefrótico/diagnóstico por imagen , Anciano , Membrana Basal/patología , Terapia Combinada , Complicaciones de la Diabetes , Humanos , Inmunoterapia , Inflamación , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Masculino , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/patología , Síndrome Nefrótico/terapia , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Receptores de Fosfolipasa A2/inmunología , Rituximab/farmacología , Tomografía Computarizada por Rayos XRESUMEN
Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic stem cell transplantation (Allo-SCT). Chronic GVHD, which typically presents more than 100 days after Allo-SCT, can resemble manifestations of autoimmune disease; however, there are only a few reports on the development of Crohn's disease (CD) after Allo-SCT. Here, we report a case of steroid-refractory CD after umbilical cord blood transplantation (CBT), which was dramatically improved with administration of anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibodies. A 21-year-old woman with refractory Hodgkin lymphoma underwent CBT and achieved complete remission. About 1 year after CBT, she complained of intermittent abdominal pain and bloody diarrhea, and colonoscopy revealed multiple longitudinal colonic ulcers with a cobblestone appearance; thus, based on the colonoscopy findings, she was diagnosed with CD. We considered a CD-like manifestation of gastrointestinal GVHD and initially administered steroids, but the therapeutic effect was poor. Then, we administered anti-TNF-alpha antibodies, infliximab, and then adalimumab, which resulted in rapid improvement of abdominal symptoms, with no recurrence despite discontinuation of this therapy. Anti-TNF-alpha antibodies are effective for CD after Allo-SCT, which can be considered as a subsequent complication of GVHD.
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Anticuerpos Monoclonales/administración & dosificación , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Enfermedad de Crohn/etiología , Enfermedad de Crohn/terapia , Enfermedad de Hodgkin/terapia , Adalimumab/administración & dosificación , Terapia Combinada , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Humanos , Inmunoterapia/métodos , Infliximab/administración & dosificación , Inducción de Remisión , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenRESUMEN
The purpose of the present study was to determine whether objective gait test scores obtained using a tri-axial accelerometer can detect subjective improvement in gait as determined by the patient after carotid endarterectomy (CEA). Each patient undergoing CEA for ipsilateral internal carotid artery stenosis determined whether their gait was subjectively improved at six months after CEA when compared with preoperatively. Gait testing using a tri-axial accelerometer was also performed preoperatively and six months postoperatively. Twelve (15%) of 79 patients reported subjectively improved gait. Areas under the receiver operating characteristic curve for differences between pre- and postoperative test values in stride time, cadence, and ground floor reaction for detecting subjectively improved gait were 0.995 (95% confidence interval (CI), 0.945-1.000), 0.958 (95%CI, 0.887-0.990), and 0.851 (95%CI, 0.753-0.921), respectively. Cut-off points for value differences in detecting subjectively improved gait were identical to mean -1.7 standard deviation (SD) for stride time, mean +1.6 SD for cadence, and mean +0.4 SD for ground floor reaction of control values from normal subjects. Objective gait test scores obtained using the tri-axial accelerometer can detect subjective gait improvements after CEA. When determining significant postoperative improvements in gait using a tri-axial accelerometer, optimal cut-off points for each test value can be defined.
Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Análisis de la Marcha , Anciano , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Resultado del TratamientoRESUMEN
Accurate risk assessment to determine the eligibility for allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with adult T cell leukemia (ATL) is necessary to improve survival outcomes. The controlling nutritional status (CONUT) score predicts prognosis in several tumors; however, the prognostic significance of the CONUT score in ATL remains unclear. The present study investigated the correlation between the CONUT score and the survival outcomes of transplant-eligible ATL patients. Mogamulizumab, a humanized monoclonal antibody against C-C chemokine receptor 4, was recently identified as a promising salvage chemotherapy agent for transplant-ineligible ATL patients. We therefore evaluated the efficacy of mogamulizumab in transplant-ineligible ATL patients. Patients diagnosed with aggressive ATL (acute lymphoma of unfavorable chronic type) between January 2008 and March 2017 at Saga University Hospital, Japan, were retrospectively enrolled. Of 54 patients, 25 were < 70 years of age and 14 received allo-HCT. The median overall survival (OS) and non-relapse mortality (NRM) rate at 1 year among patients receiving allo-HCT were 1685.5 days and 30% in those with a CONUT score 0-3 (n = 10) and 184.5 days and 100% in those with a score ≥ 4 (n = 4) (p = 0.017, OS; p = 0.064, NRM). Older patients who received mogamulizumab had a significantly longer OS (n = 12, median 432 days) than those who did not receive mogamulizumab (n = 17, median 199 days) (p = 0.018). The CONUT score was identified as a prognostic tool for transplant-eligible ATL patients, and mogamulizumab improved OS in transplant-ineligible ATL patients.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/terapia , Anciano , Anciano de 80 o más Años , Aloinjertos , Anticuerpos Monoclonales Humanizados/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma Extranodal de Células NK-T , Neoplasias Cutáneas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asparaginasa/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Japón/epidemiología , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/mortalidad , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/mortalidad , Esteroides/administración & dosificaciónRESUMEN
It has been well documented that patients may develop cytokine-release syndrome (CRS) following the administration of monoclonal antibodies, such as chimeric antigen receptor-modified T cell. Cytokine-release syndrome is a common complication in patients who have received haploidentical donor allogeneic haematopoietic cell transplantation (haplo-HCT). Although severe CRS after haplo-HCT is a potentially life-threatening toxicity, a standard treatment has not been established. Cytokine blockade with tocilizumab, an anti-IL-6 receptor antibody, has been effective for the treatment of patients with CRS after chimeric antigen receptor-modified T-cell treatment and has also improved CRS after haplo-HCT. A 46-year-old man was diagnosed with haemophagocytic syndrome associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma. Salvage chemotherapy was unsuccessful; consequently, he received haplo-HCT. On day +4, he developed grade 3 CRS, subsequently high-dose corticosteroid initiated. Nevertheless, on day +6, he developed grade 4 CRS, resulting in requirement for ventilator support and multiple vasopressors. Corticosteroid could not improve severe CRS; therefore, tocilizumab was administered on day +14. Serum C-reactive protein level transiently decreased and weaned multiple vasopressors. Although CRS improved, he developed candidaemia; consequently, he died on day +34. Tocilizumab could transiently improve severe CRS after haplo-HCT. Although tocilizumab may have led to the improvement of CRS, a remaining concern is whether it inhibited the patient's ability to mount antifungal immunity, leading to their demise.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Citocinas/efectos de los fármacos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Trasplante Haploidéntico/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/farmacología , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/cirugía , Masculino , Persona de Mediana Edad , Síndrome , Trasplante Haploidéntico/métodosRESUMEN
Amino acids are present in the blood. In healthy people, the concentrations of these amino acids in the blood are maintained at stable levels. However, different diseases disturb the balance of amino acids in the blood in different ways. AminoIndex® is a service that uses the latest medical technology to measure the concentration of amino acids in the blood to check a person's health and detect various diseases. It is now possible to conduct an AminoIndex® Cancer Screening (AICS®) test that can detect cancer from early stages. The AICS® measures the concentrations of amino acids in the blood and statistically analyzes the differ- ences in the balance of amino acid concentrations between healthy people and those with cancer. As a result, we can simultaneously screen for certain types of cancer. Currently, the test can screen for gastric cancer, lung cancer, colorectal cancer, prostate cancer (in males), breast cancer (in females), and uterine/ovarian cancer* (in females). The application of AminoIndex® technology will spread through the fields of medicine, such as in the treat- ment of metabolic syndrome. (*The uterine/ovarian cancer test determines the overall risk of having any of the three cancers: cervical cancer, endometrial cancer, and ovarian cancer, and can not determine the individual risk of having each cancer.) [Review].
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Aminoácidos/sangre , Neoplasias/diagnóstico , Detección Precoz del Cáncer , Ejercicio Físico , Conducta Alimentaria , Humanos , Factores de RiesgoAsunto(s)
Revascularización Cerebral , Enfermedad de Moyamoya/psicología , Enfermedad de Moyamoya/cirugía , Adulto , Circulación Cerebrovascular , Cognición/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/diagnóstico por imagen , Tomografía de Emisión de PositronesAsunto(s)
Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 22/genética , Infecciones por Virus de Epstein-Barr/genética , Translocación Genética , Cariotipo Anormal , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos B/química , Linfocitos B/virología , Cromosomas Humanos Par 19/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Linfoma de Células B Grandes Difuso/virología , Masculino , Metilprednisolona/administración & dosificación , Prednisona/administración & dosificación , ARN Neoplásico/análisis , ARN Viral/análisis , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónAsunto(s)
Cromosomas Humanos Par 11/ultraestructura , Cromosomas Humanos Par 14/ultraestructura , Inmunosupresores/efectos adversos , Linfoma de Células B Grandes Difuso/inducido químicamente , Metotrexato/efectos adversos , Proteínas de Neoplasias/análisis , Neprilisina/análisis , Proteínas de Fusión Oncogénica/análisis , Proteínas Proto-Oncogénicas c-bcl-6/análisis , Translocación Genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 14/genética , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Inmunosupresores/uso terapéutico , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Metotrexato/uso terapéutico , Proteínas de Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Prednisolona/administración & dosificación , Inducción de Remisión , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Treatment of chronic myeloid leukemia (CML) has been drastically changed by the emergence of the ABL tyrosine kinase inhibitor (TKI), imatinib mesylate. However, resistance and intolerance have frequently been reported, particularly in patients with advanced-stage disease. Point mutations within the ABL kinase domain that interfere with imatinib binding are the most critical cause of imatinib resistance. To overcome this resistance, four second-generation ATP competitive ABL TKIs, dasatinib, nilotinib, bosutinib and bafetinib, have been developed. Dasatinib and nilotinib also demonstrated higher efficacy than imatinib in previously untreated CML patients in chronic phase. Despite promising clinical results, the frequently observed mutant T315I is not effectively targeted by any of the second-generation ABL TKIs. Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harbouring T315I. CML treatment is rapidly progressing and further evolution is surely expected. Moreover, it was recently reported that some CML patients who achieved sustained complete molecular response could stop TKI. CML may become the first human cancer to be conquered solely with oral medicines.
Asunto(s)
Resistencia a Antineoplásicos/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-abl/genética , Benzamidas/uso terapéutico , Dasatinib , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Piperazinas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas c-abl/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Tiazoles/uso terapéuticoRESUMEN
Recent advances in the treatment of lymphoid leukemias have incorporated molecular targeted drugs (CD20-targeting rituximab and BCR-ABL tyrosine kinase inhibitors) into the traditional chemotherapeutic agents. This article reviews novel molecular targeted therapies for patients with lymphoid leukemias including acute lymphoblastic leukemia, chronic lymphocytic leukemia, hairly cell leukemia and HTLV-I-related adult T-cell leukemia. Investigational agents that will be discussed in this review include inotuzumab, blinatumomab, alemtuzumab, ofatumumab, ibrutinib, idelalisib, bafetinib, lenalidomide, ABT-199 and mogamulizumab. Novel approaches warrant continued research to improve outcomes for patients with lymphoid leukemias.
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Leucemia Linfoide/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Adulto , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células PrecursorasRESUMEN
17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.
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Enfermedades del Sistema Nervioso Central , Esmalte Dental/anomalías , Diabetes Mellitus Tipo 2 , Enfermedades Renales Quísticas , Masculino , Humanos , Adulto , Japón , Cara , HeterocigotoRESUMEN
A 76-year-old man presented with skin plaque and splenic nodules, and diffuse large B-cell lymphoma (DLBCL) with infiltration of T-cells was suspected based on the skin lesions. The disease showed indolent clinical behavior for three months, when systemic lymphadenopathy rapidly evolved. An inguinal lymph node biopsy revealed DLBCL with abundant infiltration of T follicular helper (TFH) cells. A polymerase chain reaction-based analysis of immunoglobulin variable heavy chain showed that the skin, splenic nodules, and inguinal lymph node shared the same clone. This case indicates that the dysregulated infiltration of TFH cells in the tumor microenvironment accelerates the lymphomagenesis and progression of DLBCL.