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1.
Hematol Oncol ; 39(3): 336-348, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33583077

RESUMO

Transplant-ineligible relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) patients represent an unmet medical need. Polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADG), with bendamustine- rituximab(BR) has recently gained approval for these patients, both in the USA and Europe, based on the GO29365 phase IIb trial. Real-life data with Pola are extremely limited. We report the outcomes of 61 Greek patients, who received Pola-(B)R mainly within a compassionate use program. Treatment was given for up to six 21-day cycles. Bendamustine was omitted in three cases due to previous short-lived responses. Fourty-nine rrDLBCL(efficacy cohort-EC) and 58 rr aggressive B-NHL (safety cohort-SC) patients received at least 1 Pola-BR cycle. Twenty-one (43%) patients of the EC responded with 12/49 (25%) CR and 9/49 (18%) PR as best response. Median progression-free survival, overall survival and duration of response were 4.0, 8.5, and 8.5 months respectively, while 55% of patients experienced a grade ≥3 adverse event, mainly hematologic. Treatment discontinuations and death during treatment were mainly due to disease progression. Twenty-two (41%) patients received further treatment; 11/22 are still alive, including one after CAR-T cells, and two after stem cell transplantation. Our data confirm that Pola-BR is a promising treatment for rrDLBCL patients, inducing an adequate response rate with acceptable toxicity. Pola-BR could be used as bridging therapy before further consolidative treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Intervalo Livre de Doença , Feminino , Grécia/epidemiologia , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Taxa de Sobrevida
3.
Eur J Haematol ; 95(4): 342-51, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25645321

RESUMO

OBJECTIVE: The aim of this study was to evaluate bone involvement in patients with Gaucher disease (GD) and to propose a novel semi-quantitative magnetic resonance imaging (MRI) staging. METHODS: MRI of the lumbar spine, femur, and tibia was performed in 24 patients with GD and 24 healthy controls. We also measured circulating levels of C-C motif ligand-3 (CCL-3) chemokine, C-telopeptide of collagen type-1 (CTX), and tartrate-resistant acid phosphatase isoform type-b (TRACP-5b). RESULTS: We used the following staging based on MRI data: stage I: region of interest (ROI) 1/2 of normal values and bone infiltration up to 30%; stage II: ROI 1/3 of normal values and bone infiltration from 30 to 60%; stage III: ROI 1/4 of normal values and bone infiltration from 60% to 80%; and stage IV: detection of epiphyseal infiltration, osteonecrosis and deformity regardless of the ROI's values. All but two patients had abnormal MRI findings: 9 (37.5%), 6 (25%), 3 (12.5%), and 4 (16.7%) had stages I-IV, respectively. Patients with GD had elevated chitotriosidase, serum TRACP-5b, and CCL-3 levels (P < 0.001). CONCLUSIONS: We propose an easily reproducible semi-quantitative scoring system and confirm that patients with GD have abnormal MRI bone findings and enhanced osteoclast activity possibly due to elevated CCL-3.


Assuntos
Doenças Ósseas/diagnóstico , Doenças Ósseas/etiologia , Doença de Gaucher/complicações , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Biomarcadores , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Feminino , Doença de Gaucher/diagnóstico , Doença de Gaucher/genética , Doença de Gaucher/terapia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
4.
JACC Adv ; 2(2): 100277, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38938303

RESUMO

Background: Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives: The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods: Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. Results: Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = -0.20, 95% CI: -0.07 to -0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). Conclusions: Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

5.
Biomedicines ; 10(2)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35203419

RESUMO

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have applied a broad panel of FISH probes in 965 newly diagnosed MM (NDMM) and 44 PCL cases of both types to reveal the particular cytogenetic differences among the three plasma cell dyscrasias. In order to evaluate the frequency and patterns of clonal evolution, the same FISH panel was applied both at diagnosis and at the time of first relapse for 81 relapsed MM patients and both at MM diagnosis and during sPCL transformation for the 19 sPCL cases described here. pPCL was characterized by frequent MYC translocations and t(11;14) with a 11q13 breakpoint centered on the MYEOV gene, not commonly seen in MM. sPCL had a higher number of FISH abnormalities and was strongly associated with the presence of del(17p13), either acquired at the initial MM stage or as a newly acquired lesion upon leukemogenesis in the context of the apparent clonal evolution observed in sPCL. In clinical terms, sPCL showed a shorter overall survival than pPCL with either standard or high-risk (t(4;14) and/or t(14;16) and/or del(17p13) and/or ≥3 concomitant aberrations) abnormalities (median 5 months vs. 21 and 11 months respectively, p < 0.001), suggesting a prognostic stratification based on cytogenetic background. These observations proved relevant in the NDMM setting, where higher levels of circulating plasma cells (CPCs) were strongly associated with high-risk cytogenetics (median frequency of CPCs: 0.11% of peripheral blood nucleated cells for high-risk vs. 0.007% for standard-risk NDMM, p < 0.0001). Most importantly, the combined evaluation of CPCs (higher or lower than a cut-off of 0.03%), together with patients' cytogenetic status, could be used for an improved prognostic stratification of NDMM patients.

6.
Leuk Res Rep ; 17: 100318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35539018

RESUMO

We report an extremely rare case of extranodal B-cell NHL: DLBCL (diffuse large B-cell non-Hodgkin lymphoma), stage IVE, presenting with heart and bilateral adrenal involvement. On admission, adrenal and thorax imaging identified large bilateral adrenal masses and a 4.6 cm mass in the right atrium wall. An adrenal biopsy revealed the presence of a DLBCL, with triple expression of bcl2, bcl6, C-MYC(+70%). Following six cycles of systemic immunochemotherapy with R-DA-EPOCH, and high methotrexate dose for CNS prophylaxis a marked decrease of lymphoma infiltration was observed. The selection of the appropriate treatment modality can lead to profound response and improve patient's outcome.

7.
Pharmaceuticals (Basel) ; 15(8)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36015155

RESUMO

Modern treatment modalities in hematology have improved clinical outcomes of patients with hematological malignancies. Nevertheless, many new or conventional anticancer drugs affect the cardiovascular system, resulting in various cardiac disorders, including left ventricular dysfunction, heart failure, arterial hypertension, myocardial ischemia, cardiac rhythm disturbances, and QTc prolongation on electrocardiograms. As these complications may jeopardize the significantly improved outcome of modern anticancer therapies, it is crucial to become familiar with all aspects of cardiotoxicity and provide appropriate care promptly to these patients. In addition, established and new drugs contribute to primary and secondary cardiovascular diseases prevention. This review focuses on the clinical manifestations, preventive strategies, and pharmaceutical management of cardiotoxicity in patients with hematologic malignancies undergoing anticancer drug therapy or hematopoietic stem cell transplantation.

8.
Am J Hematol ; 85(11): 894-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20872550

RESUMO

Anthracyclines have contributed to a marked increase in survival in different types of cancer [1,2]. Unfortunately, they are associated with dose-dependent cardiotoxicity and heart failure (HF) [3­8]. Change to a weekly dosage schedule with slow infusions has been tested, a strategy that requires more frequent hospital visits and increased storage resources[7,9]. Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [10]. Beta-blockers and angiotensin converting enzyme(ACE) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity,but have not been tested in long-term prospective, randomized,controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [11­16]. We investigated doxorubicin-induced clinical or subclinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment. We examined whether cardiotoxicity was related to the treatment or any other variable. We found that HF was less frequent under concomitant treatment than no treatment, especially in the metoprolol group, but the differences were not significant. No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact. The marginal benefit seen with metoprolol should be investigated further.


Assuntos
Doxorrubicina/toxicidade , Enalapril/administração & dosagem , Linfoma/tratamento farmacológico , Metoprolol/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1 , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina , Antibióticos Antineoplásicos , Cardiotônicos , Quimioprevenção/métodos , Doxorrubicina/uso terapêutico , Enalapril/farmacologia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Humanos , Linfoma/complicações , Masculino , Metoprolol/farmacologia , Pessoa de Meia-Idade , Pré-Medicação/métodos
9.
Eur J Obstet Gynecol Reprod Biol ; 254: 181-187, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33032100

RESUMO

OBJECTIVE: Pregnancy is reported to exacerbate manifestations in women with Gaucher Disease (GD). The objective of our study was to examine the outcome of pregnancies of Caucasian women with GD in a Greek Center of Excellence on GD. STUDY DESIGN: Fifteen GD women were enrolled. All data were collected by questionnaire: fertility, normal pregnancies, spontaneous-elective-therapeutic abortions, maternal -neonatal status, birth weight and chromosomal abnormalities. RESULTS: Forty-one pregnancies were reported among 15 women: mean conception age (±SD) 27.7 ±â€¯5.8years (range 17-42years). Thirty-seven conceptions were spontaneous, 4 were after in vitro fertilization (IVF). Twenty three out of the 41 (56.1 %) pregnancies were normal. Eleven out of the 41 (26.8 %) pregnancies resulted in spontaneous abortions, 3 out of 41 (7.3 %) in elective and 3 out of 41 (7.3 %) in therapeutic abortions. Therapeutic abortions were due to worsening of GD manifestations, fetal chromosomal abnormalities and GD type 2 embryo. Nine out of 15 women had maternal complications: gestational diabetes, splenomegaly, hepatomegaly, thrombocytopenia, osteoporosis and postpartum hemorrhage. Twenty three out of the 41 pregnancies resulted in live births. Nine out of the 23 (39.1 %) deliveries were caesarian sections and 14 out of 23 (60.9 %) were vaginal. The total number of neonates was 24 (14 females / 10 males). Mean gestational age on delivery (± SD) was 35.9 ±â€¯3.1 weeks (range 26-38 w). Average female birth weight (±SD) was 2671.4 ±â€¯851.6 g (range 900-4100 grams) and male was 3333 ±â€¯996.4 g (range 1930-4700 grams). Nine out of 24 (37.5 %) neonates had low birth weight. Average low birth weight (±SD) was 1931.1 ±â€¯420.52 g (range 900-2300 grams). Twenty out of the 24 (83.3 %) neonates were healthy. Four out of 24 neonates had neonatal complications: two neonates had GD type 1, one had GD type 3 and one neonate died two days after delivery (it was born at 26 weeks). Four neonates were hospitalized in incubators at the intensive neonatal care unit due to low birth weight. Thirty-nine women did not receive enzyme replacement therapy for GD during pregnancy, while, in two pregnancies, treatment was discontinued during the first trimester and re-administered after that. Mean first menarche age (±SD) was 13.6 ±â€¯0.7 years. Thirteen out of 15 women were menopausal, mean menopausal age (± SD) 466 ±â€¯2.6 years. CONCLUSION: Most of GD women experience uncomplicated pregnancies and deliver normal, healthy infants, although the rate of complications and the rate of abortions is high in this population.


Assuntos
Doença de Gaucher , Adolescente , Adulto , Criança , Feminino , Fertilização in vitro , Doença de Gaucher/complicações , Doença de Gaucher/epidemiologia , Grécia/epidemiologia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Adulto Jovem
10.
Cytometry B Clin Cytom ; 98(5): 412-420, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32497402

RESUMO

BACKGROUND: There are no immunophenotypic guidelines for the investigation of MYC-rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC-rearranged lymphomas and guide cytogenetic analysis. METHODS: We reviewed diagnostic samples from patients diagnosed with Burkitt lymphoma (BL), double-hit lymphoma (DHL), MYC-rearranged diffuse large B-cell lymphoma (MYC-DLBCL), and standard (non-MYC-rearranged) DLBCL over the last decade in our Institution. Using flow cytometry (with antibodies CD20, CD10, CD38, bcl-2, Ki-67, FMC-7, CD43, CD27, CD79b, CD23, and CD22) we determined antigen% expression and median-fluorescence intensity ratios (MFIR). The forward scatter (FS) and side scatter (SS) characteristics of tumor B-cells were compared with normal T-cells (B/T ratios) for patients with MYC-rearranged lymphomas. RESULTS: We identified 51 patients of whom 14 had BL, 10 had DHL (6 MYC+/BCL2+; 4 MYC+/BCL6+), 8 MYC-DLBCL, and 19 standard DLBCL. The significant differences (p <.05) were: higher CD38% in BL than standard DLBCL; higher CD10% in BL and DHL versus MYC-DLBCL and standard DLBCL; higher CD10MFIR in BL than MYC-DLBCL and standard DLBCL; higher Ki-67% in BL than DHL and MYC-DLBCL; higher bcl-2% in DHL than BL; higher FMC-7% in BL than MYC-DLBCL and standard DLBCL; and lower SS (B/T) ratio in DHL than MYC-DLBCL. CONCLUSIONS: The combination of CD38% > 90, CD10% > 80, CD10MFIR > 10, bcl-2% < 30, and Ki-67% > 70 was characteristic of BL. "Deviation" from these cut-offs should raise suspicion for DHL and, therefore, BCL2 and/or BCL6 FISH is required. We also found that a diagnosis of DHL rather than of MYC-DLBCL was significantly associated with CD10% > 60, Ki-67% > 50, and SS (B/T) <1.5.


Assuntos
Linfoma de Burkitt/diagnóstico , Citometria de Fluxo , Linfoma de Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imunofenotipagem/métodos , Linfoma de Células B/genética , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade
11.
JACC CardioOncol ; 2(5): 758-770, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34396292

RESUMO

BACKGROUND: There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES: The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS: Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS: MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (ß = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (ß = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS: Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

12.
Int J Lab Hematol ; 41(3): 364-372, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30730614

RESUMO

INTRODUCTION: In B-acute lymphoblastic leukemia (B-ALL), the identification of cytogenetic prognostic factors is important for stratifying patients into risk groups and tailoring treatment accordingly. The purpose of this study was to propose flow cytometric (FCM) scoring systems (SSs) for predicting t(12;21)(p13;q22), t(9;22)(q34;q11), t(11q23), and t(1;19)(q23;p13.3) translocations. METHODS: We analyzed retrospectively the FCM immunophenotype of 377 patients with B-ALL with regard to the major cytogenetic findings revealed by interphase fluorescence in situ hybridization (i-FISH). Comparing descriptive data on the expression of each antigen and performing receiver operating characteristic (ROC) analysis, we identified the most reliable predictive markers for each translocation and sought to establish a specific SS for each translocation, based on specific antibody panels. RESULTS: CD27, CD9, CD66c, CD10, CD25, and CD34 were employed for the prediction of t(12;21), CD25, CD38, CD34, and CD66c for t(9;22), NG2, CD10, CD15, CD34, and CD20 for t(11q23), and CD34, cµ, CD123, and CD66c for t(1;19). The sensitivity and specificity, respectively, of each predictive score were 89.29% and 96.15% for t(12;21), 75.00% and 88.19% for t(9;22), 84.21% and 99.04% for t(11q23), and 85.71% and 92.71% for t(1;19). CONCLUSION: Four highly specific and significantly sensitive FCM-obtained SSs are proposed for the prediction of the four major translocations observed in patients with B-ALL. Prospective evaluation of the proposed SSs could lead to a better targeted cytogenetic investigation and therefore to more cost-effective laboratory practice.


Assuntos
Biomarcadores Tumorais , Rearranjo Gênico , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Translocação Genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Análise Citogenética/métodos , Feminino , Citometria de Fluxo/métodos , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Prognóstico , Curva ROC
13.
Blood Cells Mol Dis ; 41(2): 196-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18501647

RESUMO

Plasmalogens represent a unique type of phospholipids characterized by the presence of a vinyl-ether bond at the sn-1 position of the glycerol backbone. Peroxisomes are essential in their biosynthesis. Their suggested functions include protection against oxidative stress, participation in signal transduction, membrane fusion events, cholesterol transport and membrane trafficking, processes known to be disturbed in sphingolipidoses. We here report on red blood cell membrane plasmalogen levels in Gaucher disease patients. Plasmalogen levels were measured as their dimethylacetal derivatives (DMA) by gas chromatography in lipid extracts of erythrocytes from 15 patients. Their relative amount was estimated as the ratio between C18:0 DMA and methylstearate (C18:0), as well as C16:0 DMA and methylpalmitate (C16:0). Statistically significant lower levels of both plasmalogen species were observed in Gaucher disease patients compared to normal individuals. Furthermore, a negative correlation between plasmalogen levels and chitotriosidase was observed in the patients, which was statistically significant for the C18:0 species. Upon therapy, a significant rise of plasmalogen levels and fall in chitotriosidase activity was observed. However, C18:0 DMA/C18:0 was still significantly lower in Gaucher disease patients compared to controls and the negative correlation to chitotriosidase persisted. At both time points there was no indication of an overt peroxisomal dysfunction, very long chain fatty acid, phytanate and pristanate levels being normal. In conclusion, reduced plasmalogen levels that show a significant rise following treatment and a negative correlation to total disease burden, as expressed by chitotriosidase activity, are observed in Gaucher disease.


Assuntos
Membrana Eritrocítica/química , Doença de Gaucher/sangue , Plasmalogênios/análise , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromatografia Gasosa , Ácidos Graxos/análise , Doença de Gaucher/tratamento farmacológico , Hexosaminidases/sangue , Hexosaminidases/metabolismo , Humanos , Lactente , Pessoa de Meia-Idade
14.
Leuk Lymphoma ; 59(10): 2439-2446, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29411666

RESUMO

Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q). ASXL1 mutations were also found in other genetically defined AML subgroups such as those with t(9;22), inv(3)/t(3;3), t(8;21) or t(15;17); however, none of our inv(16) cases carried ASXL1 mutations. We detected two previously unreported ASXL1 mutations, p.IIe593Val and p.Cys688Tyr. Our findings suggest that ASXL1 mutations tend to cluster with specific clinical and cytogenetic profiles of AML patients.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Segunda Neoplasia Primária/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Fatores Etários , Idoso , Carcinogênese/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucocitose/sangue , Leucocitose/genética , Masculino , Pessoa de Meia-Idade , Mutação
15.
JIMD Rep ; 18: 107-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25308560

RESUMO

We investigated peripheral blood T-lymphocyte subpopulations and intracellular expression of IFN-γ, IL-4, IL-10, and IL-13, by whole blood flow cytometry, in 22 type I Gaucher disease (GD) patients. Results were compared with those of 19 sex- and age-matched controls. Patients with GD exhibited decreased frequencies and absolute numbers of CD3+/CD4+ helper T lymphocytes (40.8 ± 9.8% vs. 49.4 ± 5.7%, p = 0.002, and 0.77 ± 0.33 vs. 1.04 ± 0.28 × 10(9)/µL, p = 0.011), as well as increased frequencies of CD3+CD8+ suppressor T lymphocytes (23.8 ± 8.0% vs. 18.4 ± 3.8%, p = 0.010), resulting in a significantly decreased CD4/CD8 cell ratio (p < 0.001). Moreover, they had significantly increased percentages of IFNγ-producing both CD4+ and CD8+ T cells (p = 0.0003 and p = 0.023, respectively), implying a TH-1 polarization pattern. Finally, patients with GD had decreased percentages and absolute numbers of CD4+CD25(dim) T lymphocytes (p = 0.033 and p = 0.007, respectively), of CD4+CD25(high) T lymphocytes (p = 0.039 and p = 0.016, respectively), and of CD4+CD25(high)FOXP3+ regulatory T cells (p = 0.036 and p = 0.019, respectively). Our results demonstrate that patients with GD have a significant numerical impairment of T-helper lymphocytes and a constitutive TH1 direction pattern of activation of both CD4+ and CD8+ cells, associated with a significant decrease of T-regs. Ineffective T-cell control may explain the chronic inflammatory reaction and the increased incidence of lymphoid malignancies, which have been repeatedly reported among patients with GD.

16.
Leuk Res ; 34(4): 438-46, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19793612

RESUMO

We present a cohort of 22 patients with type 2 dendritic cell (DC2) acute leukemia (or blastic plasmacytoid dendritic cell neoplasm-BPDCN, as it has been recently named), diagnosed in Greece over the past 12-year period, according to the main clinical and immunophenotypic features of this entity. Four additional cases are discussed, classified as leukemia of ambiguous lineage (LAL), because of the simultaneous detection of a CD56 negative DC2 population and of a second myeloid precursor cell population. The morphological features and cytogenetic findings of the typical BPDCN cases were similar to those previously described. Acute lymphoblastic leukemia-type chemotherapeutic regimens were more efficient in controlling the disease. Immunophenotyping of typical BPDCN cases revealed CD4(+), CD56(+), HLA-DR(+) and CD123(bright) neoplastic cells, in the absence of major B-, T- and myeloid-associated markers, while the phenotype of the four cases characterized as LAL highlights the risk of misdiagnosis. Based on our experience, we propose a flow cytometric algorithmic approach for the distinction of typical BPDCN from certain types of acute myeloid leukemia, but also for the identification of acute myeloid leukemia, admixed with CD56 negative DC2 cells, which could be misdiagnosed as BPDCN.


Assuntos
Células Dendríticas/patologia , Leucemia/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Citogenética , Diagnóstico Diferencial , Feminino , Grécia , Humanos , Imunofenotipagem/métodos , Leucemia/genética , Leucemia/imunologia , Leucemia/patologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia
17.
Cancer ; 97(7): 1721-31, 2003 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-12655529

RESUMO

BACKGROUND: Postremission therapy is critical in maintaining complete remission (CR) in patients with de novo acute myelogenous leukemia (AML). The aim of this trial was to compare allogeneic stem cell transplantation (SCT), high-dose cytarabine (ara-C; HiDAC), and autologous SCT as postremission therapy in patients with de novo AML. METHODS: One hundred twenty patients age

Assuntos
Citarabina/administração & dosagem , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
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