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1.
Cytometry B Clin Cytom ; 98(3): 216-225, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31697027

RESUMO

BACKGROUND: The assessment of minimal residual disease (MRD) by flow cytometry (FC) has a prognostic impact in acute myeloid leukemia (AML), despite the low sensitivity in predicting relapse. Nonetheless, the role of leukemic-associated immunophenotypes (LAIPs)-related specificity on the sensitivity of MRD has not been clarified yet. In this respect, we accomplished this study. METHODS: LAIP-frequencies of bone marrow samples from healthy donors and patients after treatment were quantified and subdivided in "categories of specificity" named as: "strong," "good," and "weak." At the following, the diagnostic performance of MRD was investigated in terms of sensitivity, specificity, predictive values, likelihood ratio (LR). RESULTS: "Strong" LAIPs were identified by CD7, CD2, CD4, and CD56 markers while "weak" LAIPs, independently of coexpressed markers, were mainly observed in CD33+ cells. MRD identified patients with significantly low DFS and OS but showed a low sensitivity in predicting relapse. Interestingly, majority of recurrences was noticed in patients with two LAIPs and lacking of "strong" LAIPs or only with one "good" LAIP. Thus, only patients showing one "strong" or two "good" LAIPs were considered suitable for MRD monitoring and selected to be further investigated. In this subset, positive MRD predicted a poor prognosis. Moreover, a higher sensitivity, negative predictive value (NPV) and LR- were observed after comparison with the previous series. CONCLUSIONS: These data highlight the relevant role of LAIP classification in "categories of specificity" in improving the sensitivity of MRD as assessed by FC.


Assuntos
Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual/diagnóstico , Adulto , Idoso , Antígenos CD7/imunologia , Medula Óssea/imunologia , Medula Óssea/patologia , Antígenos CD2/imunologia , Antígenos CD4/imunologia , Antígeno CD56/imunologia , Linhagem da Célula/imunologia , Feminino , Voluntários Saudáveis , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/etiologia , Neoplasia Residual/imunologia , Recidiva , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia
2.
Leuk Res ; 46: 18-25, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27107744

RESUMO

In patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), the anti-thrombotic and/or cytoreductive treatment in the follow-up may affect the evaluation of the pro-thrombotic weight of the clinical and biological characteristics at diagnosis. In order to avoid this potential confounding effect, we investigated the relationship between prior thrombosis (PrTh: thrombosis occurred before diagnosis and before treatment) and the characteristics at diagnosis in 977 thrombocythemic patients with MPN, reclassified according to the WHO 2008 criteria. PrTh occurred in 194 (19.9%) patients, with similar rates in the different MPNs. In multivariate analysis, PrTh rate was significantly related to minor thrombocytosis (platelets ≤700×10(9)/L), leukocytosis (leukocytes >10×10(9)/L), higher hematocrit (HCT >45%), JAK2 V617F mutation, older age, and cardiovascular risk factors (CVRFs). The highest PrTh rate (33.9%) was associated with the coexistence of minor thrombocytosis and leukocytosis. Of note, the inverse relationship between PrTh rate and platelet count is consistent with the hemostatic paradox of thrombocytosis. In conclusion, this analysis in MPN patients disclosed the unbiased characteristics at diagnosis with a pro-thrombotic effect. Moreover, it suggests that the optimal control of blood cells counts, and CVRFs might be of utmost importance in the prevention of thrombosis during the follow-up.


Assuntos
Transtornos Mieloproliferativos/complicações , Trombocitose/complicações , Trombofilia/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Leucocitose , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Contagem de Plaquetas , Fatores de Risco , Trombose/prevenção & controle , Adulto Jovem
3.
Br J Haematol ; 172(1): 111-21, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26458240

RESUMO

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Avaliação de Medicamentos/métodos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Compostos de Nitrosoureia/administração & dosagem , Compostos de Nitrosoureia/efeitos adversos , Compostos Organofosforados/administração & dosagem , Compostos Organofosforados/efeitos adversos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Sistema de Registros , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Adulto Jovem
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