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1.
J Immunother ; 40(7): 253-264, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28763347

RESUMO

The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation. Twenty patients with MM were enrolled in the study. Following stimulation and maturation, moDCs were tested for their capacity to induce T-helper 1 and cytotoxic T lymphocyte responses in vitro. Both strategies were effective in the induction of myeloma-specific cytotoxic T lymphocyte and T-helper 1 cells, as demonstrated by cytotoxicity and ELISpot assays. On the whole, T-cell responses were observed in 18 cases by either method of DC pulsing. We conclude that both whole-tumor antigen approaches are efficient in priming autologous antimyeloma T-cell responses and warrant further study aiming at the development of individualized DC vaccines for MM patients.


Assuntos
Antígenos de Neoplasias/imunologia , Células Dendríticas/imunologia , Monócitos/imunologia , Mieloma Múltiplo/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores , Células Cultivadas , Citocinas/metabolismo , Citotoxicidade Imunológica , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/metabolismo , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
2.
Biol Blood Marrow Transplant ; 18(3): 451-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21803018

RESUMO

Patients with relapsed/progressed Hodgkin's lymphoma (HL) following autologous hematopoietic cell transplantation (AHCT) may not have an invariably dismal outcome as previously considered. In a multicenter retrospective study, we evaluated 126 patients who relapsed/progressed after a median of 5 (1-132) months post first AHCT. Management consisted of irradiation, chemotherapy ± irradiation, second HCT, or palliation. Currently, 53 of 126 (42%) patients are alive for a median of 32 months since relapse/progression and 44 (35%) of them remain progression-free. Interval of <12 months to relapse/progression, presence of B-symptoms, and disease refractoriness at first AHCT failure adversely influenced overall survival (P < .05). The type of treatment had no impact on survival. Furthermore, to predict the outcome at the time of relapse/progression, we constructed a prognostic model based on 3 factors: interval of <12 months from first AHCT to relapse/progression, presence of B-symptoms, and pre-AHCT disease refractoriness. Patients with 0 to 1 factors achieved a median survival of 70 months compared to 17 months only in those with 2 to 3 factors (P < .001). This study, the largest reported to date, suggests that selected patients with relapse/progression after first AHCT can be rescued with current treatment modalities. However, relapsed/progressed HL following AHCT still poses a therapeutic challenge, and prospective trials are needed to determine the most appropriate approach in this setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/cirurgia , Transplante Autólogo/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
3.
Leuk Res ; 32(3): 481-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17669490

RESUMO

Cases of leukemia associated with Turner syndrome (TS) are rare. Here we report three TS patients with leukemia including one case of T-large granular lymphocyte leukemia (T-LGL), one rare case of coexistence of chronic lymphocytic leukemia (CLL) and idiopathic myelofibrosis (IMF) and one case of a patient with AML-M2 who received autologous stem cell transplantation (SCT). T-LGL and coexistence of CLL and IMF associated with TS are reported for the first time while the last case represents the first report of SCT in a leukemia patient with TS. Our cases and the limited data of previously reported leukemia patients with TS suggest that TS is not associated with a specific type of leukemia and that presentation, clinical course and response to treatment are similar to that of the non-TS leukemia patients. However, these patients may have a higher risk of liver complications. Interestingly, in the mosaic TS patients, the abnormal clones were restricted to the monosomic 45,X cells, indicating that the leukemic clones possibly originate from the monosomic cell line. Even in cases with no additional chromosome abnormalities, the ratio of X/XX cells in bone marrow cells was significantly increased compared to that in constitutional karyotype, indicating that monosomic cells possibly provide a survival advantage for leukemia cells or that reduced programmed cell death may be responsible for the expansion of the monosomic cells.


Assuntos
Leucemia/complicações , Síndrome de Turner/complicações , Adulto , Feminino , Humanos , Leucemia Linfocítica Granular Grande/complicações , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Mieloide Aguda/complicações , Pessoa de Meia-Idade , Monossomia , Resultado do Tratamento
4.
J Reprod Med ; 52(10): 959-61, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17977175

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a curative treatment modality for many patients with malignant hematologic diseases. Despite impressive advances in the management of allo-HSCT, graft vs. host disease (GvHD) is a frequent complication that significantly contributes to the morbidity and mortality associated with transplantation and is a significant obstacle to overcome. CASE: An unusual case of hematocolpometra secondary to vaginal stenosis occurred as a manifestation of chronic GvHD. CONCLUSION: Management of vaginal stenosis and stricture formation as a manifestation of chronic GvHD consists of surgery with lysis of adhesions. Return of anatomic distortion to normal is followed by vaginal dilatation. Later, local estrogen cream and sexual activity help to avoid further adhesion formation.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Hematometra/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Doenças Vaginais/etiologia , Adulto , Constrição Patológica , Feminino , Humanos , Doenças Vaginais/patologia , Doenças Vaginais/cirurgia
5.
Cancer Genet Cytogenet ; 133(1): 87-9, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11890996

RESUMO

We report on a case of refractory anemia with trilineage dysplasia and an unbalanced der(1)t(1;10) that resulted in trisomy of the long arm of chromosome 1 (1q) and monosomy of the short arm of chromosome 10 (10p). Fluorescence in situ hybridization showed that the rearranged chromosome contained the centromeres of both chromosomes 1 and 10, leading to a dic(1;10). To our knowledge, a dicentric chromosome involving chromosomes 1 and 10 has never been described in hematological malignancies.


Assuntos
Cromossomos Humanos Par 10 , Cromossomos Humanos Par 1 , Monossomia , Síndromes Mielodisplásicas/genética , Trissomia , Adulto , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino
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