RESUMO
OBJECTIVES: In this study, we aimed to determine the clinicopathological factors influencing the treatment-free period in patients with follicular lymphoma (FL) using a watch-and-wait (WW) strategy. METHODS: We retrospectively assessed histopathological parameters of 82 patients with FL. RESULTS: The median time from diagnosis to WW discontinuation was 62 months (range, 3-138), and median follow-up was 86 months (range, 3-183). Intermediate or high-risk Follicular Lymphoma International Prognostic Index score (P = .012), non-duodenal-type (P = .011), higher numbers of interfollicular CD4+ (P = .038) and intrafollicular FOXP3+ cells (P = .024) in the tumor microenvironment, and Ki-67 index ≥10% (P = .031) were significant adverse factors for WW discontinuation in univariate analyses. CONCLUSION: Patients with adverse factors for WW discontinuation should be carefully observed during follow-up.
Assuntos
Linfoma Folicular/diagnóstico , Microambiente Tumoral , Conduta Expectante , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Transformação Celular Neoplásica , Progressão da Doença , Feminino , Humanos , Incidência , Linfoma Folicular/epidemiologia , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Rituximab/farmacologia , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Excisional biopsy (EB) is considered the gold standard for lymphoma diagnosis. Although recent advances in interventional radiology enable sampling with core-needle biopsy (CNB), only few studies evaluated the utility of CNB compared to that of EB. METHODS: We analyzed patients with lymphoma who had a diagnostic biopsy at the National Cancer Center Hospital during 2002-2017. We investigated the clinical and pathological characteristics of CNB in 2017. RESULTS: The proportion of CNB utility in total biopsy procedures had increased from 11 to 48% during the 15 years. In 2017, CNB was opted more frequently than EB for a biopsy of superficial, abdominal, or anterior mediastinal lesions. Only one out of 72 patients who had CNB required re-biopsy with EB because of insufficiency. The incidence of complications was comparable between CNB and EB: 2 (4%) cases of minor bleeding with CNB and 1 (8%) case of minor bleeding with EB. The median time from the first visit to biopsy was significantly shorter with CNB (5.5 days) than with EB (15 days). CONCLUSION: There is an increasing trend in the utility of CNB. CNB is a less invasive method with shorter time to biopsy and can be considered an alternative to EB.
Assuntos
Biópsia com Agulha de Grande Calibre , Biópsia/métodos , Linfoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Biópsia com Agulha de Grande Calibre/efeitos adversos , Feminino , Hemorragia/etiologia , Humanos , Hibridização in Situ Fluorescente , Linfadenopatia/patologia , Linfoma/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
CD20- change after rituximab-containing therapy is considered one of the main reasons of rituximab resistance of B-cell non-Hodgkin lymphomas (B-NHLs). However, the clinicopathological characteristics of B-NHL with CD20- change are not entirely understood. In this study, 252 B-NHL patients who were CD20+ at initial diagnosis, whose diseases relapsed or were refractory after rituximab-containing therapy, and who were re-biopsied between 2000 and 2018, were included. The median number of rituximab administration was 11 (range, 1-48). Completely negative (cCD20-) and partially negative (pCD20-) change of CD20 was observed in 49 (20%) and 16 (6%) cases, respectively. Among cCD20- and pCD20- cases, 74% and 62% of the cases changed to CD20- at the second relapse or later, respectively. Overall survival was significantly shorter in cCD20- follicular lymphoma (FL) cases than in CD20+ FL cases. Seven histopathological patterns, such as CD20- change without histological change, histological transformation (HT) to CD20- diffuse large B-cell lymphoma, and proliferation of plasmablastic/plasmacytoid tumor cells, were associated with CD20- change. HT occurred more frequently in FLs with CD20- change than in FLs continuously expressing CD20 (P < 0.0001), regardless of the timing of HT. Nine out of 25 cases (36%) showed regain or heterogeneous regain of CD20 expression. In conclusion, 20% and 6% of the 252 B-NHL cases show cCD20- and pCD20- changes with 7 histological patterns after rituximab-containing therapy. Because changes in morphology and CD20 expression after rituximab-containing therapy vary, and recovery of CD20 expression is not rare, careful follow-up and re-biopsy in B-NHL patients are recommended.
Assuntos
Antígenos CD20/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/imunologia , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/química , Estudos de Coortes , Feminino , Humanos , Linfoma de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Epstein-Barr virus (EBV) infection is associated with pathogenesis of various cancers, including extranodal natural killer/T-cell lymphoma, nasal type (ENKL). ENKL tumor cells are positive for EBV-encoded RNA1 (EBER1), which is the most useful marker to identify ENKL tumor cells in histopathology. Currently, EBER1 in situ hybridization (ISH) is recommended to evaluate bone marrow (BM) involvement of ENKL. However, the actual burden of EBER1-positive cells in normal BM specimens remains unclear. In the present study, we performed EBER1 ISH on 111 BM specimens, which were obtained during an initial staging procedure in patients with EBV-negative cancers and were also negative for BM involvement. One or more EBER1-positive cells per whole specimen were observed in 38 specimens (34%). The number of EBER1-positive cells was distributed as follows: single positive cell, n = 17; two positive cells, n = 13; three positive cells, n = 3; and four positive cells, n = 5. These findings suggest that four or fewer EBER1-positive cells can be observed in BM specimens of patients with non-EBV-related cancers. The clinical implications of a small number of EBER1-positive cells in BM specimens of patients with ENKL should be evaluated in further studies.
Assuntos
Medula Óssea/virologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , RNA Bacteriano/genética , Adulto , Idoso , Feminino , Humanos , Linfoma/patologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , RNA Viral , Sarcoma/patologia , Sarcoma/virologia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/virologia , Adulto JovemRESUMO
The transcription factor GATA-1-interacting protein Friend of GATA-1 (FOG1) is essential for proper transcriptional activation and repression of GATA-1 target genes; yet, the mechanisms by which FOG1 exerts its activating and repressing functions remain unknown. Forced FOG1 expression in human K562 erythroleukemia cells induced the expression of erythroid genes (SLC4A1, globins) but repressed that of GATA-2 and PU.1. A quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated increased GATA-1 chromatin occupancy at both FOG1-activated as well as FOG1-repressed gene loci. However, while TAL1 chromatin occupancy was significantly increased at FOG1-activated gene loci, it was significantly decreased at FOG1-repressed gene loci. When FOG1 was overexpressed in TAL1-knocked down K562 cells, FOG1-mediated activation of HBA, HBG, and SLC4A1 was significantly compromised by TAL1 knockdown, suggesting that FOG1 may require TAL1 to activate GATA-1 target genes. Promoter analysis and quantitative ChIP analysis demonstrated that FOG1-mediated transcriptional repression of PU.1 would be mediated through a GATA-binding element located at its promoter, accompanied by significantly decreased H3 acetylation at lysine 4 and 9 (K4 and K9) as well as H3K4 trimethylation. Our results provide important mechanistic insight into the role of FOG1 in the regulation of GATA-1-regulated genes and suggest that FOG1 has an important role in inducing cells to differentiate toward the erythroid lineage rather than the myelo-lymphoid one by repressing the expression of PU.1.
Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/genética , Regulação Leucêmica da Expressão Gênica , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Fatores de Transcrição/genética , Acetilação , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Western Blotting , Linhagem Celular , Cromatina/genética , Cromatina/metabolismo , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Histonas/metabolismo , Humanos , Células K562 , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/metabolismo , Leucemia Eritroblástica Aguda/patologia , Lisina/metabolismo , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 1 de Leucemia Linfocítica Aguda de Células T , Transativadores/metabolismo , Fatores de Transcrição/metabolismoAssuntos
Agranulocitose/complicações , Leucemia de Células T/complicações , Receptores de Antígenos de Linfócitos T gama-delta/análise , Linfócitos T/patologia , Adulto , Agranulocitose/genética , Agranulocitose/patologia , Feminino , Humanos , Leucemia de Células T/genética , Leucemia de Células T/patologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Adulto JovemAssuntos
Proliferação de Células/efeitos dos fármacos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/metabolismo , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T/metabolismo , Idoso , Doença de Hodgkin/patologia , Humanos , Masculino , Nivolumabe/administração & dosagem , Linfócitos T/patologiaAssuntos
Cadeias Pesadas de Imunoglobulinas , Mieloma Múltiplo , Segunda Neoplasia Primária , Oligopeptídeos/administração & dosagem , Proteínas de Fusão Oncogênica , Plasmocitoma , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Transplante de Células-Tronco , Neoplasias Testiculares , Idoso , Autoenxertos , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Masculino , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Plasmocitoma/genética , Plasmocitoma/metabolismo , Plasmocitoma/patologia , Plasmocitoma/terapia , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapiaRESUMO
Haploidentical hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide is an alternative treatment for aplastic anemia-paroxysmal nocturnal hemoglobinuria (PNH) syndrome with poor prognostic factors. Ravulizumab treatment for PNH before HSCT might have a beneficial effect.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Asparaginase/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Carboplatina/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Linfoma Extranodal de Células T-NK/sangue , Pessoa de Meia-IdadeRESUMO
Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed.
Assuntos
Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfócitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Masculino , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Estudos Retrospectivos , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
Introduction: Surveillance computed tomography (CT) is performed during the follow-up of patients with lymphoma who have completed initial therapy. However, studies on the clinical benefit of surveillance CT for patients with incurable subtypes, such as follicular lymphoma (FL), are limited. This study aimed to evaluate the value of surveillance CT for patients with FL after achieving the first complete response (CR) or CR unconfirmed in the rituximab era. Methods: We retrospectively reviewed the medical records of patients with FL who achieved CR with first-line treatment between 2000 and 2016 at our institution. In patients who experienced first relapse, we examined the patient's clinical characteristics at the time of relapse, subsequent therapies, and post-relapse survival, based on the method of relapse detection. Results: Of the 248 patients who achieved CR after initial therapy, 109 had a relapse, with a median follow-up of 11 years; 100 were enrolled into this study. Relapse was detected by surveillance CT in 61 patients (surveillance CT group) and by means other than surveillance CT, such as the presence of patient-reported symptoms, physical findings, and blood work-up abnormalities (non-surveillance CT group), in 39 patients. There was no significant difference in the patients' characteristics at the time of relapse between the two groups, except for a higher incidence of extranodal involvement in the non-surveillance CT group. The method of relapse detection did not affect therapeutic selection after relapse and post-relapse survival. In this study, 86.8% of the 38 patients who relapsed with only deep lesions, such as mesenteric or retroperitoneal lymph nodes, had surveillance CT-detected relapse. Conclusion: Surveillance CT did not show any clinical benefit for patients with FL in CR; however, it might lead to early detection of relapse in cases of deep lesions that cannot be identified without imaging.
RESUMO
BACKGROUND: Approximately 15% of patients with diffuse large B-cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab-containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL. METHODS: Sixty-nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R-CHOP] or relapse within 6 months of R-CHOP) (n = 41) or primary progressors (no response to R-CHOP) (n = 28). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non-germinal center B-cell-like type DLBCL, and 42% had double-expressor lymphoma (MYC and BCL2 expression). The 3-year overall survival rate was significantly poorer in the primary progressors group than in the partial responders' group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC-ASCT were primary progressors; only one patient survived without relapse. Although double-expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC-ASCT-treated patients (p = 0.002). CONCLUSIONS: We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Progressão da Doença , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Terapia de Salvação/métodos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto JovemRESUMO
A nonidentifiable mycolicibacterium was isolated from a malignant lymphoma patient treated with intensive chemoimmunotherapy. Multilocus sequence analysis showed that this isolate was close to "Mycolicibacterium (Mycobacterium) ratisbonense," but the details of this species were still unknown. Here, we report the draft genome sequence data of Mycolicibacterium sp. strain NCC-Tsukiji.
RESUMO
Ring sideroblasts are a hallmark of sideroblastic anemia, although little is known about their characteristics. Here, we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene, a gene responsible for X-linked sideroblastic anemia (XLSA). Although heterozygous female mice showed an anemic phenotype, ring sideroblasts were not observed in their bone marrow. We next established human induced pluripotent stem cell-derived proerythroblast clones harboring the same ALAS2 gene mutation. Through coculture with sodium ferrous citrate, mutant clones differentiated into mature erythroblasts and became ring sideroblasts with upregulation of metal transporters (MFRN1, ZIP8, and DMT1), suggesting a key role for ferrous iron in erythroid differentiation. Interestingly, holo-transferrin (holo-Tf) did not induce erythroid differentiation as well as ring sideroblast formation, and mutant cells underwent apoptosis. Despite massive iron granule content, ring sideroblasts were less apoptotic than holo-Tf-treated undifferentiated cells. Microarray analysis revealed upregulation of antiapoptotic genes in ring sideroblasts, a profile partly shared with erythroblasts from a patient with XLSA. These results suggest that ring sideroblasts exert a reaction to avoid cell death by activating antiapoptotic programs. Our model may become an important tool to clarify the pathophysiology of sideroblastic anemia.