RESUMO
Although recent accumulative data reveal the clinicopathogenesis of regression in methotrexate-induced lymphoproliferative disorders (MTX-LPDs), the precise understanding including this category remains controversial. In this study, we analyzed 62 patients with MTX-LPD. Forty-three patients showed regression (Reg group), with high rates of Hodgkin lymphoma (HL) and LPD (90 and 88%, respectively). Among the 43 patients of the Reg group, 14 patients (33%) relapsed. The median duration before relapse in the Reg group was 10.6 months. Although the difference of OS between the Reg and Non-Reg groups was not significantly different, relapse-free patients in the Reg group had a superior overall survival (OS). MTX duration had a significant impact on Epstein-Barr virus (EBV) infection (p = .00131). Furthermore, EBV infection was significantly related to clinical manifestations, including spleen invasion, in the regression phenomenon. Some human leukocyte antigens (HLA) alleles might affect MTX-LPD development via EBV infection, although A*2402 and DRB1*0405 might be affected as fundamental factors.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Transtornos Linfoproliferativos/patologia , Metotrexato/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Taxa de SobrevidaRESUMO
Recently, attention has been focused on methotrexate-induced lymphoproliferative disease (MTX-LPD), and atypical phenotypes are occasionally documented. We encountered two patients with rheumatoid arthritis (RA) who were diagnosed with non-specific LPD (LPD-nos). Biopsy samples were not obtained during the initial examination when the LPD development was discovered, and the patients achieved a complete response after MTX cessation (case 1) or steroid pulse therapy (case 2). However, the tumors flared up 1.5 years later, and LPD-nos was determined following biopsies of the lymph node (LN, case 1) and liver (case 2). Prednisolone was subsequently administered instead of chemotherapy; however, multiple masses, including in the spine (case 1), and severe icterus with liver dysfunction (case 2) were exacerbated within a few months. Although the re-biopsy of LN proved the presence of HL and radiation followed by aggressive chemotherapy rescued the patient (case 1), the superficially accessible biopsy site was not found, and autopsy finally revealed HL (case 2). In both cases, the underlying pathogenesis along with the B symptoms and laboratory abnormalities suggested MTX-LPD, HL in particular. Therefore, even if the pathological diagnosis does not confirm the specific LPD subtype, the administration of aggressive chemotherapy should be considered if the LPD activity flares severely.
Assuntos
Artrite Reumatoide/complicações , Doença de Hodgkin/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Recidiva , Indução de Remissão/métodosRESUMO
Thrombopoietin receptor (TPO-R) agonists have been shown to be effective in refractory chronic immune thrombocytopenia (ITP); however, their efficacy in patients under critical care is not known. We report the case of a female patient with a newly diagnosed ITP who experienced severe bleeding from an external wound. The patient was administered the standard treatments for ITP, which are high-dose intravenous immunoglobulin (IVIg) and corticosteroids. However, following failure of these treatments, we administered romiplostim on day 6 after the onset of ITP. On day 6 after the initiation of romiplostim, there was improvement in platelet count and bleeding tendency. We were subsequently able to perform a splenectomy successfully. The efficacy of TPO-R agonists in ITP has been reported in several situations, including before surgery in an ITP patient; however, the use of TPO-R for arterial bleeding with shock has not been reported. To our knowledge, the present article is a rare case report of the use of a TPO-R agonist in a patient with critical artery injury. Our data suggest that the early use of romiplostim is effective in emergency cases of newly diagnosed ITP with life-threatening bleeding, which is refractory to standard treatment.
Assuntos
Lesões das Artérias Carótidas/complicações , Hemorragia/complicações , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Idoso , Lesões das Artérias Carótidas/sangue , Lesões das Artérias Carótidas/tratamento farmacológico , Feminino , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Humanos , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangueRESUMO
Primary cardiac lymphoma is extremely rare and is associated with a poor prognosis. In most cases, cardiac involvement occurs as a late symptom and the diagnosis is thus delayed. We herein report a 35-year-old woman with cardiac diffuse large B-cell lymphoma (DLBCL) with breast infiltration. The patient was admitted to our hospital based on an initial presentation with dyspnea on exertion, chest pain, and a hard mass of the left breast. Echocardiography revealed a mass in the right atrium wall and interatrial septum, and massive pericardial effusion. ECG showed atrioventoricular block. We promptly performed a needle biopsy of the breast mass, which showed CD5-positive DLBCL, non-GCB type. The serum HIV reaction was negative. We thus diagnosed this patient as having cardiac and breast CD5-positive DLBCL, stage IVA, based on the massive pericardial effusion. The patient's prognosis was apparently poor. Therefore, she received 3 cycles of R-CHOP chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT), resulting in a complete response. In general, cardiac lymphoma is associated with high mortality and has a poor prognosis. This case demonstrates that rapid and appropriate diagnosis, and immediate intensive chemotherapy followed by PBSCT might be necessary for the treatment of extranodal lymphoma indicative of a poor prognosis.
Assuntos
Neoplasias da Mama/terapia , Neoplasias Cardíacas/terapia , Linfoma Difuso de Grandes Células B/terapia , Derrame Pericárdico/terapia , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Estadiamento de Neoplasias , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiologia , Transplante de Células-Tronco de Sangue Periférico , Resultado do TratamentoAssuntos
Artrite Reumatoide/complicações , Imunossupressores/efeitos adversos , Leucemia Mieloide/etiologia , Transtornos Linfoproliferativos/induzido quimicamente , Metotrexato/efeitos adversos , Segunda Neoplasia Primária/etiologia , Medula Óssea/patologia , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Hibridização in Situ Fluorescente , Leucemia Mieloide/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnósticoRESUMO
Despite numerous attempts to uncover the mechanism of other iatrogenic immunodeficiency-associated lymphoproliferative diseases (OIIA-LPDs), this mechanism remains poorly understood, especially in rheumatoid arthritis (RA) patients. We analyzed the data on 23 patients with LPDs and RA. Patients were categorized into three groups according to whether they had methotrexate (MTX); MTX-regressive LPDs, MTX-persistent LPDs or other drugs-mediated LPDs. The LPDs seen in OIIA-LPDs-RA might have a unique behavior to think about several rare phenotypes. The overall survival of all patients was 74% at 5 years, and those of the three groups were 100%, 64% and 60%, respectively. Among the 6 patients who died, 4 had LPDs that were detected late, and thus adequate treatment was not given. In addition, several patients with diffuse large B cell lymphoma with a complex karyotype achieved complete remission (CR). Only one among the 17 patients who achieved CR relapsed. OIIA-LPDs-RA appeared to have a better prognosis than other more common types of lymphomas. Regarding RA treatment, various anti-RA drugs were given to the patients after developing LPDs, including MTX, but no recurrent patients were documented.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Hospedeiro Imunocomprometido , Transtornos Linfoproliferativos/patologia , Metotrexato/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/metabolismo , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Aberrações Cromossômicas , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Cariótipo , Antígeno Ki-1/metabolismo , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/terapia , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
Bortezomib is a potent agent for multiple myeloma (MM); however, severe treatment-related toxicities such as peripheral neuropathy have been observed in conjunction with its use. In this study, we present the cases of 9 patients with refractory MM whose administration schedule was modified from twice weekly to an interval of once weekly or longer mainly due to adverse events. The average duration from diagnosis to the time of bortezomib induction was 56 months. The schedule was changed to the modified administration according to the physician's discretion. The average duration of modified treatment was 16 months. Six patients with IgG or IgA subtype showed more than a minor response. One patient with BJP had stable disease for 3 years, and the other BJP-type patient with extramedullary plasmacytomas showed remarkable tumor regression. The treatment-related toxicities of this strategy were mild and tolerable. To our knowledge, this is the first report of the administration of bortezomib at intervals longer than once weekly.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ácidos Borônicos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Pirazinas/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/efeitos adversos , Bortezomib , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Pirazinas/efeitos adversos , Indução de Remissão , Análise de Sobrevida , Resultado do TratamentoRESUMO
An 83-year-old woman had been suffering from palpitations and fatigue for a month. An annual screening test revealed an increased WBC count so she was referred to our hospital. CBC showed extremely elevated WBC count (186,300/microl), in which the population of blastic eosinophils was over 90%. The eosinophils expressed CD7/13/33/34/DR, and the karyotype demonstrated 47,XX,+8. The fusion gene of FIP1-LP/PDGFRalpha in peripheral blood was negative. As plural effusion due to the underlying disease progressively worsened, she was given prednisolone and hydroxyurea, but the effect was limited. Steroid pulse therapy and imatinib (100 mg/day) were administrated. As a result, a prompt response was observed. The WBC count rapidly decreased, but tumor lysis syndrome led to acute renal failure and disseminated intravasucular coagulation appeared. Supportive therapies such as artificial dialysis and transfusions were conducted, but unfortunately she died because of alveolar hemorrhage.
Assuntos
Leucemia Eosinofílica Aguda/complicações , Leucemia Eosinofílica Aguda/tratamento farmacológico , Metilprednisolona/efeitos adversos , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Síndrome de Lise Tumoral/etiologia , Injúria Renal Aguda/etiologia , Idoso de 80 Anos ou mais , Benzamidas , Coagulação Intravascular Disseminada/etiologia , Sinergismo Farmacológico , Evolução Fatal , Feminino , Humanos , Síndrome Hipereosinofílica/complicações , Mesilato de Imatinib , Metilprednisolona/administração & dosagem , Piperazinas/administração & dosagem , Derrame Pleural/etiologia , Pulsoterapia , Pirimidinas/administração & dosagemRESUMO
Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA.
Assuntos
Artrite Reumatoide/complicações , Infecções por Vírus Epstein-Barr/complicações , Leucemia Mieloide Aguda/complicações , Transtornos Linfoproliferativos/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Linhagem da Célula , Diagnóstico , Infecções por Vírus Epstein-Barr/diagnóstico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Transtornos Linfoproliferativos/diagnóstico , Masculino , Pessoa de Meia-Idade , Linfócitos T/patologiaRESUMO
We here report the case of a young Japanese woman diagnosed with chronic active Epstein-Barr virus (EBV) infection. Intensive therapy with the CHOP regimen was partially able to control virus expansion, but various central nervous system symptoms appeared and gradually progressed. EBV-encoded RNA, detected using in situ hybridization, disclosed the presence of EBV in liver and bone marrow tissue, and real-time PCR revealed the presence of EBV in the cerebrospinal fluid (CSF) and serum. CD3+CD4+CD8-CD56- T-cell expansion in the peripheral blood (PB) and CSF was also observed. Atrophic brain changes were progressive, and the patient died of central nervous system disturbance and pulmonary hemorrhage a year after diagnosis. Autopsy revealed that EBV-infected T lymphocytes with a phenotype similar to those seen in PB and CSF had infiltrated multiple organs: the lymph nodes, bone marrow, endocardium, pericardium, myocardium, spleen, liver, and spinal cord. There have been few previous reports of severe degenerative changes in the myocardium, liver, and spinal cord in patients with EBV infection. Although EBV occasionally infiltrates the central nervous system and brain, atrophic changes mediated by EBV are rare. The autopsy results of this case suggest the possibility of EBV-mediated, severe degenerative changes in multiple organs.
Assuntos
Linfócitos T CD4-Positivos/patologia , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4 , Fígado/patologia , Miocárdio/patologia , Medula Espinal/patologia , Baço/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Autopsia , Linfócitos T CD4-Positivos/imunologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Infecções por Vírus Epstein-Barr/líquido cefalorraquidiano , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Humanos , Imuno-Histoquímica , Fígado/imunologia , Fígado/metabolismo , Fígado/virologia , Miocárdio/imunologia , Miocárdio/metabolismo , Prednisona/administração & dosagem , RNA Viral/metabolismo , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/virologia , Baço/imunologia , Baço/metabolismo , Baço/virologia , Vincristina/administração & dosagemRESUMO
Basophils play an important role in allergic inflammation and are pathologically related to hematological disturbances, such as iron deficiency anemia and myeloproliferative disorders; however, they are only rarely encountered in lymphoid malignancies. Here, we report the case of a 33-year-old man with a bulky mass of the small intestine, multiple paraaortic lymphoadenopathy, pleural effusion, and ascites, who was diagnosed as a case of de novo CD5+ diffuse large B cell lymphoma (DLBCL). This patient showed a marked elevation of the basophil count in the peripheral blood, which appeared to run in parallel with the tumor burden. High dose chemotherapy followed by autologous peripheral blood cell transplantation yielded complete remission, and the patient has remained disease free for 5 years. To the best of our knowledge, this is the first report of a case of de novo CD5+ DLBCL showing marked elevation of the PB basophil count.