RESUMO
Recent large-scale genetic studies have proposed a new genetic classification of diffuse large B-cell lymphoma (DLBCL), which is clinically and biologically heterogeneous. However, the classification methods were complicated to be introduced into clinical practice. Here we retrospectively evaluated the mutational status and copy number changes of 144 genes in 177 Japanese patients with DLBCL, using targeted DNA sequencing. We developed a simplified algorithm for classifying four genetic subtypes-MYD88, NOTCH2, BCL2, and SGK1-by assessing alterations in 18 representative genes and BCL2 and BCL6 rearrangement status, integrating the significant genes from previous studies. In our cohort and another validation cohort from published data, the classification results in our algorithm showed close agreement with the other established algorithm. A differential prognosis among the four groups was observed. The NOTCH2 group showed a particularly poorer outcome than similar groups in previous reports. Furthermore, our study revealed unreported genetic features in the DLBCL subtypes that are mainly reported in Japanese patients, such as CD5-positive DLBCL and methotrexate-associated lymphoproliferative disorders. These results indicate the utility of our simplified method for DLBCL genetic subtype classification, which can facilitate the optimisation of treatment strategies. In addition, our study highlights the genetic features of Japanese patients with DLBCL.
Assuntos
Linfoma Difuso de Grandes Células B/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Povo Asiático/genética , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Japão/epidemiologia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Adulto JovemRESUMO
With increasing focus on the importance of long-term survivorship care after allogeneic hematopoietic cell transplantation (allo-HCT), more institutions have been establishing long-term follow-up (LTFU) clinics. Currently, however, with varying volumes of HCT procedures and resources, there is no standardized operation of these clinics in HCT centers. We conducted a nationwide questionnaire survey to characterize the current operation of LTFU clinics in Japan. We targeted 271 HCT centers (189 adult and 82 pediatric) that registered allo-HCT cases to the national transplant registry database. The response rate was 69%, and 117 of the 188 participating centers (62%) had an established LTFU clinic. The most frequent reason cited for not operating an LTFU clinic was a "lack of human resources," especially nurses. Most centers with an LTFU clinic targeted allo-HCT recipients, although autologous HCT survivors were followed up at 18% of adult centers and 48% of pediatric centers. Ninety-two percent of centers did not terminate LTFU at a specific time point, and 56% recommended that patients visit the LTFU clinic beyond 5 years after HCT. Fifteen of 20 pediatric centers indicated that they did not routinely refer survivors who underwent HCT at a young age to an adult HCT center for their adulthood LTFU. We found that staffing and standard practices varied widely among centers, and that most centers continued to see long-term HCT survivors at their own outpatient clinics. The development of common LTFU tools may help standardize LTFU practices and facilitate efficient transitions.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Seguimentos , Humanos , Japão , Inquéritos e Questionários , SobreviventesRESUMO
To prospectively validate the incidence, manifestations, and outcomes of graft-versus-host disease (GVHD) by National Institutes of Health criteria, we recruited 406 hematopoietic stem cell transplantation recipients at 16 transplant centers in Japan from May 2012 to June 2014. The 2-year cumulative incidence of late acute and chronic GVHD was 3.2% (nâ¯=â¯13) and 35.4% (nâ¯=â¯145), with a median onset of 3.6 and 4.7 months after transplant, respectively. The global severity at onset was mild in 30.3%, moderate in 43.5%, and severe in 26.2%. Eighty-two patients were followed up for 2 years, with 79.3% still manifesting GVHD symptoms, and 80.6% (nâ¯=â¯117) of the patients received systemic immunosuppressive treatment (IST), with a 2-year cumulative incidence of IST termination of 33.1%. Severe patients showed a significantly lower rate of IST termination than those with mild and moderate severities (mild, 38.5%; moderate, 40.9%; and severe, 17.2%). The 2-year incidence of nonrelapse mortality (NRM) and relapse was not significantly different according to the severity at onset (NRM: mild [16.6%] versus moderate [8.7%] versus severe [16.1%]; relapse: mild [14.9%] versus moderate [14.7%] versus severe [5.3%]). As a result, 2-year overall survival (OS) and GVHD-specific survival (GSS) were equivalent according to the severity at onset (mild: OSâ¯=â¯81.0%, GSSâ¯=â¯85.7%; moderate: OSâ¯=â¯84.2%, GSSâ¯=â¯92.5%; severe: OSâ¯=â¯83.9%, GSSâ¯=â¯89.2%). Our study helped identify the characteristics of late acute and chronic GVHD in Japanese patients. Further investigation is needed to identify an optimal endpoint for survival prediction.
Assuntos
Doença Enxerto-Hospedeiro , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Humanos , Incidência , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30-85 years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184 days (range 21-2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3 years. Multivariate analysis determined that age > 70 years (p = 0.012) and BMI < 18.5 kg/m2 (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings.
Assuntos
Quimioprevenção/métodos , Imunomodulação , Mieloma Múltiplo/complicações , Tromboembolia Venosa/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Índice de Massa Corporal , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/prevenção & controleRESUMO
POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range, .31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70; median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndrome POEMS/terapia , Sobreviventes , Transplante Autólogo/métodos , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/mortalidade , Resultado do TratamentoRESUMO
The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response (BCR-ABL1IS ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4-78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).
Assuntos
Quimioterapia de Consolidação , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Pirimidinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Indução de Remissão , Taxa de SobrevidaRESUMO
Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 109/L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 109/L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 109/L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 109/L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses.
Assuntos
Embolização Terapêutica , Púrpura Trombocitopênica Idiopática/terapia , Baço/irrigação sanguínea , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Resistência a Medicamentos , Resistência a Múltiplos Medicamentos , Embolização Terapêutica/efeitos adversos , Feminino , Seguimentos , Hospitais Universitários , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Púrpura Trombocitopênica Idiopática/diagnóstico por imagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/patologia , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/efeitos dos fármacos , Baço/patologia , Esteroides/uso terapêutico , Adulto JovemRESUMO
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, extravascular fluid overload, M protein, and a myriad of skin changes. The pathogenesis is poorly understood, but monoclonal plasma cells are λ-restricted and these immunoglobulin λ light chain variable (IGLV) region genes are derived from only two germlines, either IGLV1-44 or 1-40. Here we analyzed the clonal IGLV gene rearrangements of genomic DNA samples of bone marrow mononuclear cells using next-generation sequencing (NGS) to understand the clonal composition of IGLV genes in patients with POEMS syndrome (n = 30). The dominant IGLV gene rearrangement of POEMS syndrome-specific germline sequences were significantly increased in 11 POEMS patients (36.7%; IGLV1-44: n = 9, IGLV1-40: n = 2). In some cases, IGLV gene rearrangement clone was not detected as significant increase but was detected using cDNA samples by heteroduplex (HD) analysis and Sanger sequencing, suggesting that the quite small number of monoclonal plasma cells may produce large quantity of mRNA of monoclonal proteins. However, significant increase of dominant clone sizes was not directly linked to the initial disease status. On the other hand, in cases with significantly increased dominant clones, they decreased and increased accompanying with disease remission and relapse. These data demonstrate that monoclonal plasma cells are related to the pathogenesis of POEMS syndrome.
Assuntos
Rearranjo Gênico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Cadeias lambda de Imunoglobulina/genética , Síndrome POEMS/genética , Células da Medula Óssea , Células Clonais , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/imunologia , Síndrome POEMS/patologia , Plasmócitos/patologia , RNA Mensageiro/análiseRESUMO
A 60-year-old man with chronic hepatitis C was referred to our hospital with significantly elevated total protein and serum IgM (9,500 mg/dl) levels identified via a routine checkup. Blood examination revealed increased serum IgM-monoclonal protein and serum-soluble IL-2 receptor (sIL2R) levels. Computed tomography and fluorodeoxyglucose positron emission tomography revealed pulmonary masses, abnormal soft tissue masses surrounding the bilateral kidneys, and thickened mucous membrane of the bladder with high fluorodeoxyglucose uptake. Pathological examination of the pulmonary mass revealed infiltration of medium-sized lymphocytes and plasma cells. Immunohistochemical analysis revealed tumor cells positive for CD138 and IgM, with a low positive rate of Ki-67 expression. Notably, the tumor cell-surrounding lymphocytes were positive for CD20. Although the patient was initially regarded as having Waldenström's macroglobulinemia owing to the significantly increased serum IgM levels, based on positive IgH-MALT1 translocation and negative MYD88 L265P mutation findings, he was further diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Complete remission was achieved following six cycles of rituximab + CHOP therapy. This study data suggest that analysis of the MYD88 L265P mutation in tumor cells is suitable for accurately diagnosing hematopoietic malignancies with increased IgM monoclonal protein.
Assuntos
Imunoglobulina M/sangue , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Humanos , Linfoma de Zona Marginal Tipo Células B/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fator 88 de Diferenciação Mieloide/genética , Prednisona/uso terapêutico , Receptores de Interleucina-2/sangue , Indução de Remissão , Rituximab/uso terapêutico , Vincristina/uso terapêutico , Macroglobulinemia de WaldenstromRESUMO
Although autologous stem cell transplantation can achieve excellent responses in patients with POEMS syndrome, the optimal regimen for peripheral blood stem cell (PBSC) collection is still controversial. We retrospectively investigated the safety and efficacy of 41 PBSC collecting procedures in 37 patients with POEMS syndrome. PBSC mobilization was performed using cyclophosphamide + granulocyte colony-stimulating factor (G-CSF) (CG, n = 14) or G-CSF alone (G, n = 27). Twelve (85.7%) patients in the CG group and all (100%) patients in the G group received induction chemotherapy before PBSC collection. The proportions of good mobilizers (≥2.0 × 106 CD34+ cells/kg) were comparable between the 2 groups (CG versus G: 78.6% versus 70.4%, P = .71). Two (14.3%) patients in the CG group developed severe capillary leak symptoms during the PBSC mobilization period, whereas no patient in the G group experienced severe adverse events. Appropriate induction therapies followed by the G-CSF monotherapy compose an optimal strategy for PBSC collection.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Síndrome POEMS/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Ascite/induzido quimicamente , Contagem de Células Sanguíneas , Avaliação de Medicamentos , Feminino , Febre/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/induzido quimicamente , Estudos RetrospectivosRESUMO
BACKGROUND: The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. METHODS: We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). RESULTS: In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. CONCLUSIONS: Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287.
Assuntos
Antígenos CD20/análise , Contagem de Leucócitos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
We describe two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome patients with deteriorated extravascular volume overload without increased levels of vascular endothelial growth factor after the administration of cyclophosphamide + granulocyte colony-stimulating factor for stem cell mobilization. We then measured the serum levels of 27 cytokines from these cases using a multiplex suspension array system. The analysis revealed the changes of cytokine profiles before cyclophosphamide + granulocyte colony-stimulating factor and after the development of capillary leak symptoms in both cases. This may improve our current level of understanding of the pathogenesis of POEMS syndrome not driven by vascular endothelial growth factor.
Assuntos
Citocinas/sangue , Mobilização de Células-Tronco Hematopoéticas , Síndrome POEMS/sangue , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Autoenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/diagnóstico por imagem , Síndrome POEMS/terapia , Tomografia Computadorizada por Raios XRESUMO
Chronic graft versus host disease (cGVHD) remains a major problem for long survivors after allogeneic hematopoietic stem cell transplantation (HSCT). Currently, corticosteroid therapy is effective for cGVHD as the first line therapy. However, prolonged therapy with corticosteroids causes various severe adverse events. To develop the new therapeutic strategy of cGVHD, we have launched a multicenter phase I/IIa clinical trial of low dose subcutaneous interleukin-2 (IL-2) for treatment of steroid refractory cGVHD, which is constituted of 2 sequential phases (induction phase and maitanance phase). This study will provide the new therapeutic option for patients with refractory cGVHD after allogeneic HSCT.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Interleucina-2/administração & dosagem , Protocolos Clínicos , Humanos , Injeções Subcutâneas , Interleucina-2/uso terapêuticoRESUMO
A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behçet's disease. Therefore, hypercytokinemia with DS might have induced Behçet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51.
Assuntos
Antineoplásicos/efeitos adversos , Doenças do Ceco/induzido quimicamente , Íleo , Perfuração Intestinal/induzido quimicamente , Leucemia Promielocítica Aguda/tratamento farmacológico , Estomatite/induzido quimicamente , Tretinoína/efeitos adversos , Adulto , Antineoplásicos/uso terapêutico , Doenças do Ceco/patologia , Antígeno HLA-B51/imunologia , Humanos , Íleo/patologia , Leucemia Promielocítica Aguda/imunologia , Masculino , Tretinoína/uso terapêuticoRESUMO
A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post-transplantation course was uneventful, except for mild skin acute graft-versus-host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV.
Assuntos
Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4/fisiologia , Derrame Pericárdico/etiologia , Transplante de Células-Tronco de Sangue Periférico , Doença Crônica , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Transplante Homólogo , Adulto JovemAssuntos
Síndrome POEMS/mortalidade , Síndrome POEMS/terapia , Adolescente , Adulto , Idoso , Comorbidade , Exercício Físico , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto JovemAssuntos
Deferasirox/administração & dosagem , Transfusão de Eritrócitos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Sobrecarga de Ferro , Aplasia Pura de Série Vermelha , Administração Oral , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/mortalidade , Masculino , Pessoa de Meia-Idade , Aplasia Pura de Série Vermelha/mortalidade , Aplasia Pura de Série Vermelha/terapia , Taxa de SobrevidaRESUMO
We retrospectively reviewed 413 recipients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HSCT) between June 1986 and March 2013. Recipients with antibody to hepatitis B core antigen (anti-HBc) and/or to hepatitis B surface antigen (anti-HBs) were regarded as experiencing previous hepatitis B virus (HBV) infection. Clinical data of these recipients were reviewed from medical records. We defined ≥1 log IU/mL increase in serum HBV DNA from nadir as HBV reactivation in hepatitis B surface antigen (HBsAg)-positive recipients, and also defined ≥1 log IU/mL increase or re-appearance of HBV DNA and/or HBsAg as HBV reactivation in HBsAg-negative recipients. In 5 HBsAg-positive recipients, 2 recipients initially not administered with nucleos(t)ide analogues (NUCs) experienced HBV reactivation, but finally all 5 were successfully controlled with NUCs. HBV reactivation was observed in 11 (2.7%) of 408 HBsAg-negative recipients; 8 of these were treated with NUCs, and fortunately none developed acute liver failure. In 5 (6.0%) of 83 anti-HBc and/or anti-HBs-positive recipients, HBV reactivation occurred. None of 157 (0%) recipients without HBsAg, anti-HBs or anti-HBc experienced HBV reactivation. In HSCT recipients, HBV reactivation is a common event in HBsAg-positive recipients, or in HBsAg-negative recipients with anti-HBc and/or anti-HBs. Further attention should be paid to HSCT recipients with previous exposure to HBV.
Assuntos
Células-Tronco Hematopoéticas/virologia , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Ativação Viral/fisiologia , Adulto , Idoso , DNA Viral/genética , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/imunologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplantados , Ativação Viral/genética , Ativação Viral/imunologiaRESUMO
A prospective multicenter observational study of organ response was conducted in patients with chronic GVHD diagnosed by the NIH criteria. When response was assessed at 12 months (12 M) in 118 patients, 74.6% were classified as responders and 25.4% as non-responders. The skin and oral cavity were the most frequent organs used as the basis for determining overall response. The lungs, liver, and eyes were also used in 20% of patients. Non-response decisions at 12 M were most frequent in the lungs. A significantly higher percentage of responders than non-responders completed systemic treatment (24.3% vs. 3.3%, P = 0.02). Global scoring showed significant changes, with improvement in responders and worsening in non-responders throughout the observation period. Two-year transplant-related mortality, using the 12 M assessment as the landmark, was significantly worse in non-responders (28.5% vs. 2,7%, P = 0.0001), while the 2-year recurrence rate was equivalent (5.4% vs. 4.8%, P = 0.78). Consequently, the 2-year overall survival rate from the 12 M assessment was significantly better in responders than non-responders (95% vs. 65.3%, P = 0.0001). Our data suggests that patients who do not achieve a response within the first year should be candidates for clinical studies on chronic GVHD.