RESUMEN
Autologous peripheral blood stem cell transplantation(auto-PBSCT)combined with high-dose chemotherapy has been considered as the standard therapy for relapsed or induction therapy-refractory aggressive lymphomas sensitive to chemotherapy. While various regimens have been applied as the conditioning,none has yet been established as the standard. We have begun to employ high-dose ranimustine,cytarabine,etoposide and cyclophosphamide(MCVAC)regimen. The present study was undertaken to review the efficacy and safety of MCVAC. Regimen: We carried out a retrospective analysis of 20 patients diagnosed as diffuse large B-cell lymphoma. The median follow-up duration of 20 patients was 13.05 months(range, 0.57-49.5 months). The 4-year OS and PFS were 57.8% and 30.2%,respectively. Relapse was the most frequent cause of treatment failure(n=7). The major toxicities were anorexia/nausea(95%),diarrhea (75%),hypokalemia (70%). One patient died of hepatic veno-occlusive disease(VOD). The serious adverse events included hypokalemia,arrhythmia,cerebral hemorrhage,and heart failure(1 case[5%]each). There was 1 case of a late-onset adverse event: therapy-related myelo- dysplastic syndrome/acute myeloblastic leukemia(MDS/AML). MCVAC regimen was concluded as effective and well-toler- ated. However,we should carefully monitored for the possible development of VOD and MDS/AML. Further follow-up is needed to evaluate the long-term efficacy and safety.
Asunto(s)
Linfoma de Células B Grandes Difuso , Trasplante de Células Madre de Sangre Periférica , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Etopósido , Humanos , Linfoma de Células B Grandes Difuso/terapia , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante AutólogoRESUMEN
There are some reports regarding hepatitis B virus (HBV) reactivation in patients with myeloma who are HBV carriers or who have had a resolved HBV infection, and there is no standard prophylaxis strategy for these patients. We performed a retrospective multicenter study to determine the incidence and characteristics of HBV reactivation in patients with multiple myeloma. We identified 641 patients with multiple myeloma who had been treated using novel agents and/or autologous stem cell transplantation with high-dose chemotherapy between January 2006 and June 2014 at nine Japanese hospitals. The patients' characteristics, laboratory data, and clinical courses were retrieved and statistically analyzed. During a median follow-up of 101 weeks, one of eight (12.5 %) HBV carriers developed hepatitis and 9 of 99 (9.1 %) patients with resolved HBV infection experienced HBV reactivation; the cumulative incidences of HBV reactivation at 2 years (104 weeks) and 5 years (260 weeks) were 8 and 14 %, respectively. The nine cases of reactivation after resolved HBV infection had received entecavir as preemptive therapy or were carefully observed by monitoring their HBV DNA levels, and none of these cases developed hepatitis. Among patients with multiple myeloma, HBV reactivation was not rare. Therefore, long-term monitoring of HBV DNA levels is needed to prevent hepatitis that is related to HBV reactivation in these patients.
Asunto(s)
Virus de la Hepatitis B/fisiología , Hepatitis B/virología , Mieloma Múltiple/terapia , Activación Viral/fisiología , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Terapia Combinada , ADN Viral/análisis , ADN Viral/genética , Femenino , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Virus de la Hepatitis B/genética , Humanos , Incidencia , Japón/epidemiología , Masculino , Mieloma Múltiple/complicaciones , Mieloma Múltiple/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Trasplante de Células Madre/métodos , Trasplante AutólogoRESUMEN
Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.
Asunto(s)
Amiloidosis/tratamiento farmacológico , Bortezomib/uso terapéutico , Cardiopatías/tratamiento farmacológico , Anciano , Amiloidosis/complicaciones , Femenino , Cardiopatías/etiología , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
A 68-year-old female presented with shortness of breath. Chest radiography showed pleural effusion in the right side only. She was suspected of having ovarian cancer because CA125 levels were increased in the pleural effusion, and she consulted our hospital. A chest CT scan showed right pleural nodular lesions. Thoracoscopic pleural resection was performed. Histologic examination of a biopsy specimen showed the diffuse infiltration of smallâ¼medium, mature lymphocytes. These lymphocytes were found to be positive for CD20 and CD79a, but negative for CD3 by immunohistochemistry. These results were interpreted as being consistent with a diagnosis of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). She commenced chemotherapy with R-CHOP, and the pleural effusion disappeared. MALT lymphoma arising in the pleura is very rare, with only 12 published cases, and most cases have been described in Japan. CA125 levels correlated with the stage, tumor bulk, and presence of effusion. This patient exhibited a high level of CA125 that decreased with therapy.
Asunto(s)
Linfoma de Células B de la Zona Marginal/diagnóstico , Neoplasias Pleurales/diagnóstico , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Antígeno Ca-125/análisis , Ciclofosfamida/administración & dosificación , Diagnóstico Diferencial , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Proteínas de la Membrana/análisis , Derrame Pleural/tratamiento farmacológico , Derrame Pleural/etiología , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/tratamiento farmacológico , Prednisona/administración & dosificación , Rituximab , Tomografía Computarizada por Rayos X , Vincristina/administración & dosificaciónRESUMEN
A 66-year-old male was hospitalized with muscle weakness and gait disturbance. Examination revealed IgM 3,407 mg/dl (IgM, κ-type M protein) and he was diagnosed as having IgM-MGUS neuropathy. He suffered from paralysis of respiratory muscles and required a respirator support. Plasmapheresis and intravenous immunoglobulin were performed and he was weaned from the respirator. Rituximab given as 8 weekly infusions improved gait disturbance. A 71-year-old male was hospitalized with lumbago, numbness of lower extremities and gait disturbance. Examination revealed IgM 1,553 mg/dl (IgM, λ-type M protein) and he was diagnosed with IgM-MGUS neuropathy. Rituximab given as 8 weekly infusions improved gait disturbance. It was concluded that rituximab is a well-tolerated treatment that may be effective in some patients with IgM-MGUS neuropathy.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Gammopatía Monoclonal de Relevancia Indeterminada/terapia , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , gammaglobulinas/administración & dosificación , Humanos , Masculino , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Intercambio Plasmático , Rituximab , Resultado del TratamientoRESUMEN
Aflatoxin produced by Aspergillus flavus is known to be strongly related to liver injury (hepatocellular carcinoma) and immune system damage involving leukocytes. This toxin suppresses both the cell-mediated immune system and macrophage function, and decreases the production of complement and interferon molecules. PURPOSE: To evaluate the presence of aflatoxin in infectious lesions as well as how the toxin is taken up by leukocytes. METHOD: Pathological specimens from a patient who died from aspergillosis caused by aflatoxin-producing A. flavus were used. Anti-aflatoxin B1 antibody was reacted with paraffin-embedded lesion specimens from the heart, kidney, and thyroid gland of the patient and observed microscopically. RESULT: Positive reactions were detected in fungal elements and leukocytes (neutrophils and macrophages) in inflammatory lesions. CONCLUSION: Within the patient's body, A. flavus likely produced aflatoxin, which then was taken up by neutrophils and macrophages.These results suggest that leukocyte function and the immune mechanism are locally suppressed by aflatoxin.
Asunto(s)
Aflatoxinas , Aspergilosis , Aflatoxina B1 , Aspergillus flavus , Hongos , HumanosRESUMEN
Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF patients were analyzed. A total of 16 of 23 patients (69.6%) were found to have VB6 deficiency, but VB6 supplementation with pyridoxal phosphate hydrate did not elevate hemoglobin levels in deficient patients. None of the patients presented with vitamin B12, iron, or copper deficiencies. Four patients showed serum folate levels below the lower limit of normal and eight patients showed serum zinc levels below the lower limit of normal; however, these deficiencies were marginal and unlikely to contribute to anemia. Compared to VB6-sufficient patients, VB6-deficient patients showed significantly lower serum folate levels and higher serum copper levels. Studies elucidating the relationship of VB6 deficiency and etiology of PMF/sMF are warranted.
Asunto(s)
Mielofibrosis Primaria/sangre , Deficiencia de Vitamina B 6/sangre , Adulto , Anemia , Cobre/sangre , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Mielofibrosis Primaria/etiología , Estudios Prospectivos , Fosfato de Piridoxal/uso terapéutico , Deficiencia de Vitamina B 6/tratamiento farmacológicoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/terapia , Linfoma de Células B Grandes Difuso/terapia , Neoplasias del Mediastino/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Neoplasias Encefálicas/secundario , Terapia Combinada , Humanos , Linfoma de Células B Grandes Difuso/patología , Imagen por Resonancia Magnética , Masculino , Neoplasias del Mediastino/patología , Recurrencia Local de Neoplasia/diagnóstico , Dosificación Radioterapéutica , Resultado del Tratamiento , Adulto JovenAsunto(s)
Neoplasias de la Médula Ósea/secundario , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/secundario , Biomarcadores de Tumor/sangre , Neoplasias de la Médula Ósea/sangre , Neoplasias de la Médula Ósea/diagnóstico , Neoplasias de la Médula Ósea/patología , Cromogranina A/sangre , Humanos , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/sangre , Carcinoma Pulmonar de Células Pequeñas/sangre , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/patología , Sinaptofisina/sangreAsunto(s)
Enfermedades Linfáticas/patología , Sarcoidosis/patología , Enfermedades de la Médula Espinal/patología , Médula Espinal/patología , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Linfáticas/diagnóstico , Sarcoidosis/diagnóstico , Enfermedades de la Médula Espinal/diagnósticoRESUMEN
Neurological symptoms induced by the infiltration of malignant lymphoma into the nervous systems are subsumed under the term neurolymphomatosis (NL). Here, we report the case of a 30-year-old Japanese man with primary testicular lymphoma complicated, as seen in various neurological findings, by secondary NL prior to testicular swelling. Painless right scrotal enlargement was noticed more than 1 month after the appearance of neurological complications such as right upper extremity numbness, dysarthria, facial palsy, and diplopia. Proactive investigation and biopsies of extranodal sites at high risk of central nervous system infiltration of malignant lymphoma, such as the testes, should be considered when secondary NL is suspected based on imaging findings.
Asunto(s)
Suero Antilinfocítico/farmacología , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Síndromes Mielodisplásicos/patología , Anticuerpos Heterófilos/sangre , Suero Antilinfocítico/uso terapéutico , Reacciones Falso Positivas , Femenino , Humanos , Inmunoensayo/normas , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológicoRESUMEN
JAK2V617F, a gain-of-function mutation in the tyrosine kinase JAK2, is frequently detected in classical myeloproliferative neoplasms (MPNs). In the present study, we determined the JAK2V617F allele burden in Japanese MPN patients using alternately binding probe competitive-polymerase chain reaction, a highly quantitative method recently developed by our group. Although we observed strong similarities in terms of epidemiological parameters associated with the JAK2V617F allele burden between our cohort and others, we found a higher JAK2V617F allele burden in Japanese polycythemia vera (PV) patients and lower frequencies of thrombosis in Japanese MPN patients compared with previous reports. In addition, despite the presence of high red blood cell counts, some patients bearing the JAK2V617F mutation were not diagnosed as PV, as their hemoglobin values were lower than the WHO PV criterion. In these patients, the JAK2V617F allele burden was strikingly similar to that in PV patients fulfilling the 2008 WHO criteria, suggesting that these patients can be classified as PV. Although isotopic measurement of red cell mass (RCM) is required for definitive diagnosis of PV, our data suggest that precise measurement of the JAK2V617F allele burden may improve the diagnosis of PV when RCM has not been determined.