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Oncotarget ; 7(9): 10174-81, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26840087


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment -either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN.

Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Sistema Nervoso Central/patologia , Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Idoso , Criança , Feminino , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
PLoS One ; 10(6): e0129375, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26066831


Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

Síndromes Mielodisplásicas/genética , Trissomia/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 8/genética , Humanos
Vet Ophthalmol ; 18(4): 291-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25338923


OBJECTIVE: To determine the clinical outcome of corneal grafting for the treatment of feline corneal sequestrum (FCS). ANIMAL STUDIED: Domestic cats. PROCEDURES: A review of the medical records of cats that underwent keratoplasty as a treatment of FCS at the VTH-UAB, from 2002 to 2012, was carried out. RESULTS: Thirteen cats (18 eyes) of different breed, age, and gender were included. Persian cats were overrepresented (12/13;92%). There were nine males and four females, of a mean age of 3.4 years (0.7-7.1). Ipsilateral chronic corneal ulceration was reported as the most common concurrent ocular disease (6/18;33%). Keratoplasty was performed bilaterally in 5 cats (5/13;38%) and unilaterally in 8 (8/13;62%). Lamellar keratoplasty was performed in 17 eyes (17/18;95%) and full-thickness keratoplasty in 1 (1/18;5%). Mean graft size was 8.3 mm (4-11.5). Fresh homologous graft was performed in 2 eyes (2/18;11%) and frozen graft in 16 (16/18;89%). Of the latter group, homologous graft was performed in 6 eyes (6/16;37.5%) and heterologous in 10 (10/16;62.5%). In all the cats, postoperative treatment included topical antibiotics, corticosteroids, cycloplegics, and 0.2% cyclosporine A. Median follow-up time was 18.2 months, and main postoperative complications were diffuse mild epithelial pigment formation (2/18;11%), graft malacia (1/18;5%), and sequestrum recurrence (1/18;5%). Mean epithelial healing time was 19.2 days. Good visual outcome was achieved in all the eyes (100%), the majority of them having faint or mild corneal opacity (15/18;83%). CONCLUSIONS: Keratoplasty is an effective surgical treatment for FCS. The donor tissue provides excellent tectonic support to the affected corneas, with good visual and cosmetic outcome.

Doenças do Gato/cirurgia , Doenças da Córnea/veterinária , Transplante de Córnea/veterinária , Animais , Doenças do Gato/patologia , Gatos , Córnea/patologia , Doenças da Córnea/patologia , Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Feminino , Masculino , Necrose , Estudos Retrospectivos
Ann Hematol ; 93(10): 1695-703, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24824767


Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08-4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95-2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026-2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.

Medula Óssea/patologia , Linhagem da Célula , Leucemia Mieloide Aguda/patologia , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Análise Mutacional de DNA , Feminino , Hematopoese , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/mortalidade , Leucemia Mielomonocítica Aguda/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Risco , Adulto Jovem
Exp Clin Transplant ; 7(4): 218-24, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20353370


OBJECTIVES: The contribution of humoral immune response in allograft and xenograft rejection has been clearly demonstrated in recent years. For this reason, inhibition of alloantibody production has become essential in managing transplanted patients. Here, we assessed the effects of the leflunomide derivative FK778 (FK778) in the control of antibody production resulting from semiallogeneic cognate T-B-cell interactions. MATERIALS AND METHODS: BALB/c mice were tolerized at birth with semiallogeneic spleen cells from (BALB/c X C57BL/6) F1 mice, with or without overexpression of human bcl-2 transgene in B cells. These tolerized mice were treated with different dosages of FK778, either from birth, or from the third week of age, when autoantibody production was detected. The production of autoantibodies, used as markers of semiallogeneic cognate T-B - cell interactions, was evaluated at different time points during drug administration or after the interruption of treatment. RESULTS: FK778 treatment started at birth inhibited the production of semiallogeneic-driven antibodies in a dose-dependent manner. In addition, FK778 also reduced the levels of preformed circulating autoantibodies in adult mice, although the dosage required was 4 times higher than that used in neonates. However, the levels of IgG antibodies in these tolerized mice increased after FK778 withdrawal, indicating that FK778 failed to induce tolerance to semiallogeneic host CD4+ Th2 and/or donor B cells. CONCLUSIONS: Our results demonstrate the efficacy of FK778 in the control of antibody production resulting from semiallogeneic cognate T-B - cell interactions.

Alquinos/farmacologia , Autoanticorpos/sangue , Linfócitos B/efeitos dos fármacos , Imunossupressores/farmacologia , Isoxazóis/farmacologia , Nitrilos/farmacologia , Linfócitos T/efeitos dos fármacos , Tolerância ao Transplante/efeitos dos fármacos , Fatores Etários , Envelhecimento , Animais , Formação de Anticorpos , Linfócitos B/imunologia , Linfócitos B/transplante , Relação Dose-Resposta a Droga , Genes bcl-2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Linfócitos T/imunologia , Linfócitos T/transplante