RESUMEN
Cisplatin plus 5-fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5-fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib-III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m2 ) and nedaplatin (50 mg/m2 ) on days 1 and 8, and a continuous infusion of 5-fluorouracil (400 mg/m2 /day) on days 1-5 and 8-12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end-point was the completion rate of the protocol treatment. Twenty-eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty-five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment-related deaths and major surgical complications did not occur. Estimated 2-year progression-free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Taxoides/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/cirugía , Docetaxel , Esquema de Medicación , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Estudios de Factibilidad , Femenino , Fluorouracilo/efectos adversos , Humanos , Japón , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Compuestos Organoplatinos/efectos adversos , Análisis de Supervivencia , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
A 68-year-old man complained of dizziness and was referred to our hospital by his primary physician for evaluation of an elevated leukocyte count. In April 2002, soon after the chronic phase of chronic myeloid leukemia had been diagnosed, he was treated with imatinib. In March 2010, imatinib treatment was completed and the BCR/ABL fusion gene had become undetectable by real time quantitative PCR. Subsequently, leukocyte counts and the hematocrit gradually rose. In August 2012, a bone marrow aspirate showed hypercellular marrow with marked erythroid hyperplasia and the presence of the JAK2 gene V617F mutation. He was diagnosed with polycythemia vera. Phlebotomy and chemotherapy were started in addition to imatinib administration. Shortly thereafter complete blood counts returned to normal levels.
Asunto(s)
Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/uso terapéutico , Policitemia Vera/etiología , Pirimidinas/uso terapéutico , Anciano , Proteínas de Fusión bcr-abl/genética , Hematócrito , Humanos , Mesilato de Imatinib , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Recuento de Leucocitos , Masculino , Mutación , Flebotomía , Policitemia Vera/sangre , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Reacción en Cadena en Tiempo Real de la Polimerasa , Inducción de RemisiónRESUMEN
Primary hepatosplenic CD5-positive diffuse large B cell lymphoma (CD5⺠DLBCL) has recently been characterized as showing hepatosplenomegaly without lymphadenopathy, a portal and intrasinusoidal pattern of infiltration in the liver, and bone marrow invasion by lymphoma cells, without intravascular involvement. A 45-year-old man presented with fever and malaise in June 2013. Computed tomography showed hepatosplenomegaly and multiple liver tumors without lymphadenopathy. An ultrasonography-guided needle biopsy of the liver mass revealed portal and intrasinusoidal infiltration of CD5âºCD20⺠lymphoma cells and large numbers of destroyed hepatocytes. These findings were diagnostic of primary hepatosplenic CD5⺠DLBCL. Upon admission, lymphoma cells also appeared in the peripheral blood and serum hepatocyte growth factor (HGF) was markedly elevated. A bone marrow biopsy revealed extensive invasion by lymphoma cells. Seven days after admission, his laboratory data showed elevated aminotransferase and serum creatinine levels. Therefore, dose-reduced CH(O)P, with rituximab (R-CHOP) therapy, plasma exchange, and continuous hemodiafiltration, was initiated. The patient achieved complete remission after 4 courses of R-CHOP therapy. HGF is useful for predicting acute liver damage. If the HGF level is high, remission induction therapy, with plasma exchange, is necessary at an early stage.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Hepatopatías/terapia , Linfoma de Células B/terapia , Intercambio Plasmático , Enfermedad Aguda , Antígenos CD5/inmunología , Humanos , Hepatopatías/complicaciones , Hepatopatías/inmunología , Hepatopatías/patología , Linfoma de Células B/complicaciones , Linfoma de Células B/diagnóstico , Linfoma de Células B/inmunología , Masculino , Persona de Mediana Edad , Rituximab , Resultado del TratamientoRESUMEN
A 79-year-old man had been followed up since July 2003 based on a diagnosis of essential thrombocythemia (ET). The patient visited our hospital after developing a high fever and rash in August 2010, and Sweet's syndrome was diagnosed based on skin biopsy results. The bone marrow aspirate showed features like those of myelodysplastic/myeloproliferative neoplasm (MDS/MPN, unclassifiable). Administration of metenolone and azacitidine was initiated in March and May 2011, respectively, but the rash associated with Sweet's syndrome showed exacerbation. Ranimustine was therefore administered starting in July 2011 to control the blood cell count, but the rash associated with Sweet's syndrome persisted. Combination therapy with lenalidomide was initiated in September 2012, and resulted in control of the blood cell count and marked improvement of Sweet's syndrome.
Asunto(s)
Síndrome de Sweet/tratamiento farmacológico , Síndrome de Sweet/etiología , Talidomida/análogos & derivados , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/tratamiento farmacológico , Anciano , Recuento de Células Sanguíneas , Médula Ósea/patología , Quimioterapia Combinada , Humanos , Lenalidomida , Masculino , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/patología , Enfermedades Mielodisplásicas-Mieloproliferativas/etiología , Enfermedades Mielodisplásicas-Mieloproliferativas/patología , Compuestos de Nitrosourea/administración & dosificación , Piel/patología , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/patología , Talidomida/administración & dosificación , Trombocitemia Esencial/sangre , Resultado del TratamientoRESUMEN
BiRd combination therapy, which comprises clarithromycin (CAM: Biaxin®), lenalidomide (LEN: Revlimid®), and dexamethasone ( DEX), is a highly effective treatment for newly diagnosed symptomatic myeloma. However, its efficacy against recurrent myeloma refractory to combination therapy with LEN and DEX(Rd therapy) remains unclear. Here, we report on BiRd therapy administered to three patients with IgA myeloma exacerbated during Rd therapy and for whom transplantation was not indicated, by adding CAM to the Rd regimen. Because the IgA levels increased again after Rd therapy in all patients, treatment was switched to BiRd therapy. In all cases, the IgA levels decreased after switching to BiRd therapy, with no exacerbation or hematological or non-hematological toxicity observed. Thus, BiRd therapy may represent a therapeutic option for symptomatic myeloma resistant to Rd therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Claritromicina/administración & dosificación , Humanos , Inmunoglobulina A/inmunología , Lenalidomida , Masculino , Mieloma Múltiple/inmunología , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Resultado del TratamientoRESUMEN
A 71-year-old man with malaise, anorexia, and weight loss was referred to our hospital from a clinic. Abdominal computed tomography(CT)revealed bilateral adrenal masses. An ultrasound-guided percutaneous needle biopsy of the adrenal grand indicated diffuse large B-cell lymphoma. A rapid adrenocorticotropic hormone(ACTH)test revealed primary adrenal failure. Rituximab-cyclophosphamide/doxorubicin/vincristine/prednisolone(common name, R-CHOP)therapy accompanied by intrathecal treatment was initiated along with steroid replacement therapy. After the fourth courses, a CT scan showed a reduction of the adrenal masses, and there was no[18F]-fluorodeoxyglucose(FDG)uptake in the adrenal masses. The patient has remained in metabolic complete remission. Subsequently, both adrenal lymphomas were irradiated. The patient has been disease-free for 6 months after the diagnosis of primary adrenal lymphoma. The combined modality of chemoradiation therapy plus intrathecal treatment could be effective for primary adrenal lymphoma with a poor prognosis.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Linfoma de Células B Grandes Difuso/terapia , Neoplasias de las Glándulas Suprarrenales/patología , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos , Masculino , Prednisona/administración & dosificación , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with abdominal pain, heartburn, and high fever. Radiological findings, including positron emission tomography-computed tomography (PET-CT), and gastrointestinal fiberscopy, showed diffuse thickening of the peritoneum, omentum, and mesentery; however, no lymphadenopathy, hepatosplenomegaly, or gastrointestinal lesions were observed. Under suspicion of peritonitis carcinomatosa of unknown origin, exploratory laparoscopy was performed that revealed multiple white nodules and masses on the surfaces of the peritoneum, mesentery, and intestinal serosa. The histopathological and cytogenetic findings of the peritoneum revealed high-grade B-cell lymphoma, not otherwise specified, and a gain of MYC by fluorescence in-situ hybridization. The patient was treated with two cycles of R-CHOP therapy, followed by six cycles of dose-adjusted EPOCH-R therapy, and a complete metabolic response was confirmed by PET-CT. Since there are no specific radiological findings to confirm the diagnosis of PL, a histopathological diagnosis is usually required. Most PL exhibit an aggressive lymphoma phenotype and can be cured by appropriate chemotherapy. Therefore, early diagnosis and treatment are desirable.
Asunto(s)
Linfoma de Células B , Linfoma de Células B Grandes Difuso , Linfoma , Neoplasias Peritoneales , Masculino , Humanos , Anciano de 80 o más Años , Peritoneo/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Linfoma/patología , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Linfoma de Células B Grandes Difuso/patologíaRESUMEN
A 69-year-old male was referred to our hospital because of anemia, renal insufficiency, and a positive urine test for Bence-Jones protein. A bone marrow examination showed 73.7% of myeloma cells with lymphoplasmacytic morphology, the strong expressions of CD20 and CD23 by flow cytometry, and the chromosomal aberration of CCND1/IGH by FISH analysis. He was diagnosed with multiple myeloma, IgG-λ type. The initial treatment with bortezomib plus dexamethasone (BD) provided a rapid decrease in the level of IgG; however, he developed bortezomib-induced recurrent paralytic ileus accompanied by aspiration pneumonia during the second course. Interestingly, CD23 expression on myeloma cells decreased from 87.7% to 2.2% after 2 courses of BD. Negative CD23 expression was maintained following lenalidomide plus dexamethasone therapy. There are extremely few reports on CD23 expression on myeloma cells, and this is the first case report of multiple myeloma in which CD23 expression was lost after BD therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácidos Borónicos/uso terapéutico , Dexametasona/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Pirazinas/uso terapéutico , Receptores de IgE/inmunología , Anciano , Ácidos Borónicos/administración & dosificación , Bortezomib , Ciclina D1/biosíntesis , Dexametasona/administración & dosificación , Humanos , Masculino , Mieloma Múltiple/química , Pirazinas/administración & dosificaciónRESUMEN
Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab.
Asunto(s)
Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Púrpura Trombocitopénica/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Anciano , Anemia Hemolítica Autoinmune/complicaciones , Humanos , Masculino , Megacariocitos/patología , Púrpura Trombocitopénica/complicaciones , Rituximab , Trombocitopenia/complicaciones , Resultado del TratamientoRESUMEN
A 62-year-old man with transfusion-dependent severe aplastic anemia received immunosuppressive therapy (IST) with rabbit antithymocyte globulin and cyclosporine A in April 2010. However, his transfusion dependency did not improve. As more than 100 red blood cell (RBC) transfusions had been performed, he was administered iron chelation therapy (ICT) with deferasirox (DFX) to improve iron overload starting in July 2011. Consequently, both RBC and platelet transfusion dependency gradually improved concomitant with a decrease in serum ferritin. The bone marrow (BM) biopsy findings before administration of DFX showed severe iron accumulation and strong positive immunostaining for 8-OHdG, a marker of oxidative stress due to free iron. One year after ICT, the number of BM hematopoietic cells was increased and both iron deposition and oxidative stress were decreased. These findings suggest that DFX may contribute to hematological improvement in patients with IST-refractory aplastic anemia.
Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/uso terapéutico , Benzoatos/uso terapéutico , Transfusión Sanguínea , Quelantes del Hierro/uso terapéutico , Triazoles/uso terapéutico , Anemia Aplásica/etiología , Transfusión Sanguínea/métodos , Ciclosporina/uso terapéutico , Deferasirox , Humanos , Masculino , Persona de Mediana Edad , Reacción a la Transfusión , Resultado del TratamientoRESUMEN
A 49-year-old woman presented with pharyngeal and cervical lymph node swelling in December 2010. Biopsy of the pharynx demonstrated follicular lymphoma which secreted large volumes of immunoglobulin M (IgM) and transforming growth factor-ß (TGF-ß). Bone marrow aspiration yielded a dry tap, and bone marrow biopsy demonstrated myelofibrosis associated with lymphoma cells on admission. The plasma concentration of TGF-ß was elevated and monoclonal IgM gammopathy was detected. After only one course of chemotherapy with CHOP plus rituximab, remission of both lymphoma and myelofibrosis was achieved. Bone marrow aspiration became possible, and TGF-ß and IgM levels normalized. Thus, the myelofibrosis was reversible.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Mielofibrosis Primaria/tratamiento farmacológico , Macroglobulinemia de Waldenström/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Inmunoglobulina M/sangre , Linfoma Folicular/complicaciones , Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Persona de Mediana Edad , Prednisona/administración & dosificación , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/etiología , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/etiologíaRESUMEN
A 77-year-old man diagnosed with primary myelofibrosis (PMF), successfully controlled by thalidomide and prednisolone, was referred to us for massive subcutaneous bleeding involving the face, body, and all four limbs. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer, resulting in a diagnosis of acquired hemophilia A (AHA) for which he was treated with prednisolone and cyclophosphamide on admission. He developed right femoral intramuscular hemorrhage soon after immunosuppressive therapy and was treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he suffered complications of respiratory failure with increasing throat hemorrhaging. Recombinant activated factor VII (rFVIIa) was administered combined with methylprednisolone pulse therapy. Bleeding, including respiratory failure, was ameliorated with rFVIIa. Immunosuppressive rituximab therapy resolved AHA with marked efficacy. He died of Pneumocystis jiroveci pneumonitis. Autopsy showed transformation from PMF to acute myeloid leukemia.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Hemofilia A/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Mielofibrosis Primaria/tratamiento farmacológico , Anciano , Ciclofosfamida/uso terapéutico , Resultado Fatal , Hemofilia A/complicaciones , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Masculino , Mielofibrosis Primaria/complicaciones , RituximabRESUMEN
Primary malignant lymphoma of the uterine cervix is a rare disease, and the therapeutic strategy has not been clearly established. A 45-year old woman presented with vaginal bleeding and hypermenorrhea in January 2012. Physical examination revealed a mass in the pelvic cavity approximately the size of a neonate's head. Pelvic magnetic resonance imaging(MRI) showed a solid mass 11 cm in size in the uterine cervix with homogeneous low intensity on T1-weighted images, iso-high intensity on T2-weighted images, and heterogeneous iso-high intensity on gadolinium-diethylenetriaminepentaacetate(Gd- DTPA)-enhanced images. Multiple lymphadenopathy were also detected in the pelvis. The Papanicolaou smear indicated class 5 cervical cytology, and a subsequent histological examination by a punch biopsy of the cervix showed diffuse infiltration of medium- to large-sized mononuclear cells that stained positive for CD20 and CD79a and negative for CD3, CD5, and EBER. Bone marrow biopsy revealed no abnormality. Positron emission tomography-computed tomography(PET-CT)showed strong fluorodeoxyglucose(FDG)accumulation in the uterine cervix mass, and in the pelvic and right inguinal lymphadenopathy. The patient was diagnosed with diffuse large B-cell lymphoma of the uterine cervix, Ann Arbor stage II AE. She was successfully treated with 8 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) chemotherapy, and maintains a complete remission.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Prednisona/administración & dosificación , Rituximab , Neoplasias del Cuello Uterino/patología , Vincristina/administración & dosificaciónRESUMEN
TAFRO syndrome, a rare systemic inflammatory disorder, commonly develops in an acute or subacute manner, with an aggressive clinical behavior. A substantial number of cases of TAFRO syndrome presenting with abdominal pain, and adrenal abnormalities on imaging have also been reported. A 54-year-old man developed severe acute abdominal pain. Bilateral adrenal swelling was detected on computed tomography. Although the abdominal pain resolved spontaneously, a fever and anasarca were observed. The patient was eventually diagnosed with TAFRO syndrome, and corticosteroid administration resulted in remission. TAFRO syndrome should be included in the differential diagnosis of acute abdomen and adrenal abnormalities.
Asunto(s)
Abdomen Agudo , Enfermedad de Castleman , Masculino , Humanos , Persona de Mediana Edad , Abdomen Agudo/etiología , Corticoesteroides/uso terapéutico , Enfermedad de Castleman/diagnóstico , Edema/etiología , Edema/diagnóstico , Dolor Abdominal/etiologíaRESUMEN
Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment.