RESUMO
The differentiation of surface Ig- pre-B cells into surface Ig+ B cells is a critical transition in mammalian B cell ontogeny. Elucidation of the growth factor requirements and differentiative potential of human pre-B cells has been hampered by the absence of a reproducible culture system that supports differentiation. Fluorescence-activated cell sorting and magnetic bead depletion were used to purify fetal bone marrow CD10+/surface mu- cells, which contain 60-70% cytoplasmic mu+ pre-B cells. CD10+/surface mu- cells cultured for 2 d were observed to differentiate into surface mu+ cells. Analysis by Southern blotting provided direct evidence that rearrangement of kappa light chain genes occurs in culture, and flow cytometric analysis revealed the appearance of surface Ig+ B cells expressing mu/kappa or mu/lambda. Unexpectedly, the kappa/lambda ratio in differentiated cells was the inverse of what is normally observed in adult peripheral blood. Differentiation occurs in the absence of exogenous growth factors or cytokines, suggesting that a stimulus-independent differentiative inertia might characterize pre-B cells in vivo. Future use of this model will facilitate our understanding of normal and abnormal human pre-B cell differentiation.
Assuntos
Linfócitos B/citologia , Células-Tronco Hematopoéticas/citologia , Antígenos de Diferenciação/imunologia , Antígenos de Neoplasias/imunologia , Antígenos de Superfície/imunologia , Southern Blotting , Células da Medula Óssea , Ciclo Celular , Diferenciação Celular/genética , Células Cultivadas , Feto , Citometria de Fluxo , Expressão Gênica/imunologia , Rearranjo Gênico/genética , Humanos , Cadeias kappa de Imunoglobulina/genética , Técnicas In Vitro , NeprilisinaRESUMO
BACKGROUND: We aimed to assess anxiety and the psychological impact of routine surveillance scans in long-term survivors of adult aggressive lymphoma. PATIENTS AND METHODS: In this cross-sectional observational study of 70 survivors of curable adult aggressive lymphoma, we measured anxiety and the doctor-patient relationship and performed a qualitative interview (n = 30) focused on patient perception of routine follow-up imaging studies. RESULTS: Participants were diagnosed with aggressive lymphoma a median of 4.9 years (2.4-38.0 years) before enrollment. Thirty-seven percent of patients were found to meet criteria for clinically significant anxiety, which was not associated with years since diagnosis. In multivariate analysis, history of relapse and a worse doctor-patient relationship were independently associated with higher anxiety levels. Despite representing a largely cured population, in qualitative interviews patients reported fear of recurrence as a major concern and considerable anxiety around the time of a follow-up imaging scan. CONCLUSIONS: Routine surveillance scans exacerbate underlying anxiety symptoms and fear of recurrence in survivors of aggressive lymphoma. Strategies to minimize follow-up imaging and to improve doctor-patient communication should be prospectively evaluated to address these clinically significant issues.
Assuntos
Ansiedade , Medo , Linfoma/diagnóstico por imagem , Linfoma/psicologia , Recidiva Local de Neoplasia/psicologia , Sobreviventes/psicologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Seguimentos , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Estadiamento de Neoplasias , Relações Médico-Paciente , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Positron emission tomography (PET) is more accurate than computed tomography (CT) in staging and restaging of lymphoma, but both are considered necessary. Increasingly, PET is carried out with a low-dose CT scan. Many patients undergo both PET/CT and standard diagnostic CT. The clinical utility of performing both studies in patients with lymphoma was evaluated. PATIENTS AND METHODS: Patients with lymphoma who underwent concurrent PET/CT and diagnostic CT (a scan pair) were identified, and findings detected in either scan but not both were documented. Discrepancies were considered significant if they were related to either lymphoma or another disease process which potentially required intervention. RESULTS: Eighty-seven scan pairs were identified. PET/CT detected additional lesions over diagnostic CT in 30 patients, of which 11 demonstrated increased clinical stage. Lymphoma therapy changed based on PET/CT in two patients, and one occult rectal cancer was detected. In contrast, diagnostic CT detected five relevant findings, including two incidental findings (venous thrombosis) and three patients with splenic lesions, none of which could be confirmed as lymphoma. No patient had change of stage or lymphoma therapy based on diagnostic CT. CONCLUSION: In our series, diagnostic CT did not add value to staging or restaging of lymphoma when carried out concurrently with PET/CT.
Assuntos
Linfoma/diagnóstico , Fluordesoxiglucose F18 , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Reported median overall survival (OS) in patients with mantle cell lymphoma (MCL) has been reported to be just 3-4 years. As a consequence, first-line treatment has become more aggressive. Single-center studies with R-Hyper-CVAD and/or autologous stem-cell transplant (ASCT) have produced 3-year OS rates >80%, prompting many to adopt their use. We evaluated outcomes from a single-center cohort managed in a more traditional fashion. METHODS: We identified patients with MCL evaluated at Weill Cornell Medical Center since 1997, and included those with known date of diagnosis. An online social security database was used to verify survival. RESULTS: We identified 181 patients with MCL, and date of diagnosis could be determined in 111. Three-year OS from diagnosis was 86% [95% confidence interval (CI) 78% to 92%]. Median OS was 7.1 years (95% CI 63-98 months). Adequate information on therapy was available for 75 patients. Only five were treated upfront with (R)-Hyper-CVAD or ASCT while an additional four patients received one of these regimens subsequently. Treatment type had no significant effect on OS. CONCLUSION: Outcomes with standard approaches can yield similar survival to that achieved with more intensive approaches. Biases may account for the perceived superiority of aggressive strategies.
Assuntos
Biomarcadores Tumorais/análise , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Transplante de Células-Tronco , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos como Assunto , Estudos de Coortes , Terapia Combinada , Ciclofosfamida/administração & dosagem , Bases de Dados Factuais , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Radioterapia , Análise de Regressão , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
We conducted a retrospective analysis of 50 lymphoma patients (Hodgkin's disease and non-Hodgkin's lymphoma) who had an 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan after at least two cycles of salvage chemotherapy and before autologous stem cell transplantation (ASCT) at our institution. The patients were categorized into FDG-PET negative (N = 32) and positive (N = 18) groups. The median follow-up after ASCT was 19 months (range: 3-59). In the FDG-PET-negative group, the median progression-free survival (PFS) was 19 months (range: 2-59) with 15 (54%) patients without progression at 12 months after ASCT. The median overall survival (OS) for this group was not reached. In the FDG-PET-positive group, the median PFS was 5 months (range: 1-19) with only one (7%) patient without progression at 12 months after ASCT. The median OS was 19 months (range: 1-34). In the FDG-PET-negative group, chemotherapy-resistant patients by CT-based criteria had a comparable outcome to those with chemotherapy-sensitive disease. A positive FDG-PET scan after salvage chemotherapy and prior ASCT indicates an extremely poor chance of durable response after ASCT.
Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Transplante de Células-Tronco/métodos , Adulto , Idoso , Terapia Combinada/métodos , Feminino , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Terapia de Salvação/métodos , Análise de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
Although follicular lymphoma (FL) is generally responsive to conventional-dose chemotherapy, improved survival in patients with this disease has been difficult to demonstrate. High-dose chemo/radiotherapy followed by autologous stem-cell transplantation (ASCT) can improve response rates, although its effects on survival remain controversial. Between 1990 and 2003, we transplanted 49 patients with low-grade FL at our institution. Twenty-two patients (45%) had undergone histologic transformation at the time of ASCT. In all, 44 patients (90%) had relapsed disease and five patients (10%) were resistant to chemotherapy at the time of transplantation. After ASCT, 30 patients (61%) were in complete remission (CR). The median overall survival (OS) has not been reached, while the median event-free survival (EFS) is 2.4 years. At a median follow-up of 5.5 years (longest 12.4 years), a plateau has been reached with 56% of patients remaining alive, and 35% event-free. ASCT was well tolerated except for two (4%) treatment-related deaths. In multivariable analysis, CR after ASCT and age less than 60 years are the best predictors of EFS and OS. ASCT is thus a safe therapeutic approach in FL, resulting in long-term EFS and OS for some patients, even with transformed disease.
Assuntos
Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Folicular/terapia , Linfoma não Hodgkin/terapia , Sobreviventes , Adulto , Fatores Etários , Idoso , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Transplante AutólogoRESUMO
Information regarding treatment of post-transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab and/or chemotherapy for PTLD for response, time to treatment failure (TTF) and overall survival (OS). Thirty-five patients met inclusion criteria. Twenty-two underwent rituximab treatment, with overall response rate (ORR) 68%. Median TTF was not reached at 19 months and estimated OS was 31 months. In univariable analysis, Epstein-Barr virus (EBV) positivity predicted response and TTF. LDH elevation predicted shorter OS. No patient died of rituximab toxicity and all patients who progressed underwent further treatment with chemotherapy. Twenty-three patients received chemotherapy. ORR was 74%, median TTF was 10.5 months and estimated OS was 42 months. Prognostic factors for response included stage, LDH and allograft involvement by tumor. These factors and lack of complete response (CR) predicted poor survival. Twenty-six percent of the patients receiving chemotherapy died of toxicity. Rituximab and chemotherapy are effective in patients with PTLD who fail or do not tolerate RI. While rituximab is well tolerated, toxicity of chemotherapy is marked. PTLD patients requiring therapy beyond RI should be considered for rituximab, especially with EBV-positive disease. Chemotherapy should be reserved for patients who fail rituximab, have EBV-negative tumors or need a rapid response.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Anticorpos Monoclonais Murinos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
Fetal bone marrow B lineage cells representing multiple stages of B cell development were isolated by two-color cell sorting and analyzed for immunoglobulin H and T-cell receptor (TCR) gamma and delta gene rearrangements. Analysis of CD10+/surface mu- cells using a JH probe revealed a high frequency of rearrangements; some of these rearrangements used the 3' D region gene DQ52. Analysis of CD10+/surface mu- cells revealed no detectable TCR-gamma or -delta rearrangements, nor were TCR-delta rearrangements detected in CD10+/surface mu+ cells, despite the limited repertoire of these genes. These observations are surprising given the high frequency of TCR delta/gamma rearrangements in B cell precursor acute lymphoblastic leukemia, and identify a potential difference in patterns of gene rearrangement that distinguish normal and leukemic B cell precursors.