Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 735
Filtrar
1.
Ann Hematol ; 99(5): 913-924, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32065290

RESUMO

Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital abnormalities, bone marrow failure (BMF), and high incidences of malignancies. FA mosaicism arises from reversion or other compensatory mutations in hematopoietic cells and may be associated with BMF reversal and decreased blood cell sensitivity to DNA-damaging agents (clastogens); this sensitivity is a phenotypic and diagnostic hallmark of FA. Uncertainty regarding the clinical significance of FA mosaicism persists; in some cases, patients have survived multiple decades without BMF or hematologic malignancy, and in others hematologic failure occurred despite the presence of clastogen-resistant cell populations. Assessment of mosaicism is further complicated because clinical evaluation is frequently based on clastogen resistance in lymphocytes, which may arise from reversion events both in lymphoid-specific lineages and in more pluripotent hematopoietic stem/progenitor cells (HSPCs). In this review, we describe diagnostic methods and outcomes in published mosaicism series, including the substantial intervals (1-6 years) over which blood counts normalized, and the relatively favorable clinical course in cases where clastogen resistance was demonstrated in bone marrow progenitors. We also analyzed published FA mosaic cases with emphasis on long-term clinical outcomes when blood count normalization was identified. Blood count normalization in FA mosaicism likely arises from reversion events in long-term primitive HSPCs and is associated with low incidences of BMF or hematologic malignancy. These observations have ramifications for current investigational therapeutic programs in FA intended to enable gene correction in long-term repopulating HSPCs.


Assuntos
Células da Medula Óssea/metabolismo , Anemia de Fanconi , Neoplasias Hematológicas , Células-Tronco Hematopoéticas/metabolismo , Mosaicismo , Células da Medula Óssea/patologia , Anemia de Fanconi/sangue , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Anemia de Fanconi/terapia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Humanos
2.
Ann Biol Clin (Paris) ; 77(6): 681-684, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31859645

RESUMO

In 2020, accreditation of molecular tests according to ISO 15189 is a requirement for all French medical laboratories. For many years, the GBMHM group (French Group of Molecular Biologists in Hematology) supports this approach through organization of external quality evaluation campaigns, and by publishing recommendations that have allowed the accreditation of the most frequent molecular tests for most laboratories. However, some molecular abnormalities concerns very few patients (and sometimes a single patient), and therefore cannot be evaluated in the same way, because of the lack of external quality controls or inter-laboratory comparisons. In order to allow the accreditation of these rare analyzes, the GBMHM proposes recommendations, based on the fact that analyzes using the same methodology than those already accredited by an extensive validation process, may be accredited without the need for full analytical validation. In particular, assays based on quantitative PCR or endpoint PCR may be accredited after verification of primer specificity, repeatability and/or reproducibility, and the determination of detection or linearity limits. These recommendations, by defining the validation approach for rare molecular abnormalities, make it possible to extend the requirement of accreditation for rare tests, to provide the best patient care.


Assuntos
Acreditação/métodos , Análise Mutacional de DNA , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise Mutacional de DNA/métodos , Análise Mutacional de DNA/normas , França , Frequência do Gene , Neoplasias Hematológicas/sangue , Humanos , Laboratórios/organização & administração , Laboratórios/normas , Oncologia/organização & administração , Oncologia/normas , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Guias de Prática Clínica como Assunto , Controle de Qualidade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sociedades Científicas/organização & administração , Sociedades Científicas/normas
3.
Exp Oncol ; 41(4): 357-362, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31868326

RESUMO

AIM: Currently there are some large-scale studies of elevated total vitamin B12 in relation to diseases and their prognosis. Aim of this retrospective study was to determine association of increased B12 as an additional diagnostic marker of oncohematological diseases by a statistical analysis of clinical data of 79,524 patients. MATERIALS AND METHODS: Overall Latvian population representative data on B12  testing in 79,524 patients were obtained from laboratory database. The following exclusion criteria were applied: fluctuating B12 results within a three-month period, elevated (> 100 U/L) alanine transaminase or aspartate transaminase, hepatitis (HAV, HBV, and HCV) infection, reduced glomerular filtration rate (< 45 mL/min/1.73 m2). As a control group, individuals with normal B12 level and any oncologic diagnosis (solid cancer or hematological malignancies) were selected. RESULTS: After application of step-by-step exclusion filters, 1,373 patients were left with significantly increased level of plasma B12 (> 1,700 pg/mL). Odds ratios for oncohematological diseases in total and myeloid leukemia (including acute, chronic and unspecified) in patient group with elevated B12 were found to be 6.0 (95% CI 4.7-7.6; p < 0.0001) and 19.2 (95% CI 13.1-28.0; p <0.0001), respectively, as compared to the control group. CONCLUSION: Elevated total B12 could be considered as a potential marker for oncohematological disorders.


Assuntos
Neoplasias Hematológicas/sangue , Leucemia Mieloide/sangue , Vitamina B 12/sangue , Biomarcadores Tumorais/sangue , Estudos de Coortes , Neoplasias Hematológicas/epidemiologia , Humanos , Letônia/epidemiologia , Leucemia Mieloide/epidemiologia
4.
Clin Lab ; 65(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532106

RESUMO

BACKGROUND: Bone marrow core biopsy is a routine component of comprehensive marrow evaluation, and adequacy criteria have been recommended. However, the effectiveness of these adequacy criteria for diagnostic bone marrow evaluation needs to be reassessed in the current era of extensive ancillary testing. We aimed to determine the impact of core biopsy length and intertrabecular area of evaluable bone marrow on overall adequacy for diagnostic marrow evaluation at our tertiary care institution. METHODS: Five hundred sequential cases of iliac crest bone marrow sampling were identified by retrospective re-view at our tertiary care institution. In this cohort, 470 core biopsies were obtained for histologic evaluation. Data including gross core biopsy length, number of intertrabecular 40x high power fields of evaluable marrow, and other pathologic/clinical parameters were compiled. RESULTS: The mean core biopsy length was 1.2 cm, and only 23% measured the recommended ≥ 1.5 cm. However, 96% of the core biopsies were interpretable and contributed to the comprehensive bone marrow evaluation. Notably, 100% of biopsies with ≥ 5.5 intertrabecular areas were contributory. Ancillary testing including immunophenotypic, cytogenetic, and/or molecular studies were performed in > 99% of cases. CONCLUSIONS: When histology was integrated with ancillary testing, the overall diagnosis was substantially limited in only 0.4% of cases and material deemed entirely insufficient in 0.4%. The number of intertrabecular 40x areas of evaluable marrow is a better predictor of adequacy than core biopsy length, and adequacy criteria should be revised in this era of extensive ancillary testing.


Assuntos
Exame de Medula Óssea/métodos , Doenças Hematológicas/diagnóstico , Neoplasias Hematológicas/diagnóstico , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Exame de Medula Óssea/normas , Criança , Pré-Escolar , Feminino , Doenças Hematológicas/sangue , Neoplasias Hematológicas/sangue , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
5.
Exp Hematol ; 77: 1-5, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31472170

RESUMO

Adult hematological malignancies, such as acute myeloid leukemia, are thought to arise through the gradual acquisition of oncogenic mutations within long-lived hematopoietic stem cells (HSCs). Genomic analysis of peripheral blood DNA has recently identified leukemia-associated genetic mutations within otherwise healthy individuals, an observation that is strongly associated with age. These genetic mutations are often found at high frequency, suggesting dominance of a mutant HSC clone. Expansion of clones carrying other mutations not associated with leukemia or larger chromosomal deletions was also observed. This clinical observation has been termed clonal hematopoiesis, a condition associated with increased risk of both hematological malignancy and cardiovascular disease. Here, we discuss the identification of clonal hematopoiesis and its implications on human health, based on the May 2019 International Society for Experimental Hematology New Investigator Committee Webinar.


Assuntos
DNA Tumoral Circulante , Neoplasias Hematológicas , Hematopoese/genética , Leucemia , Mutação , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Humanos , Leucemia/sangue , Leucemia/diagnóstico , Leucemia/genética
6.
Eur J Haematol ; 103(5): 472-477, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31390488

RESUMO

INTRODUCTION: In this study, we analyzed the changes of thrombin generation as marker of coagulation activation and von Willebrand factor (vWF) levels as a marker of endothelial activation in patients undergoing chemotherapy, autologous, or allogeneic HSCT. We studied possible associations to triggering factors, including acute GVHD, thrombosis, time to engraftment, and bleeding complications. METHODS: Seventy-six patients treated for hematologic malignancies at the University Hospital Basel between 2005 and 2008 took part in this study. Blood samples were collected before the start of chemotherapy or conditioning regime (median day -2), in an early phase (median day + 12), and at a later point in time (median day + 24). RESULTS: Thrombin generation decreased in all three groups to about 50% of the initial value. Patients undergoing autologous or allogeneic HSCT showed significantly (P = .026 and P = .01) higher vWF levels than patients undergoing chemotherapy. Eighteen patients (42%) receiving allogeneic HSCT developed GVHD, vWF levels in patients with GVHD were significantly (P = .008) higher than in patients without GVHD. DISCUSSION: Patients receiving autologous or allogeneic HSCT had significantly higher vWF levels in the acute phase after the transplant than patients receiving chemotherapy alone, implicating a persistent stimulation of the endothelium, possibly within the context of GVHD.


Assuntos
Biomarcadores Tumorais/sangue , Endotélio Vascular/metabolismo , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Hemostasia , Proteínas de Neoplasias/sangue , Trombina/metabolismo , Fator de von Willebrand/metabolismo , Adolescente , Adulto , Idoso , Aloenxertos , Autoenxertos , Endotélio Vascular/patologia , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade
7.
Ann Biol Clin (Paris) ; 77(4): 397-406, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418701

RESUMO

Immunoglobulin light chains are called free when they are not linked with heavy chains to form a whole immunoglobulin. Quantification of free light chains is a part of the French national authority for health guidelines for diagnostic and follow-up of light chain, oligo or non-secretory myeloma and AL amyloidosis. Most recently, the World health organisation had included free light chains quantification in prognostic criteria for monoclonal gammopathy of undetermined significance. However the literature bring to light some other potential indications of this analysis in the exploration of monoclonal gammopathy, also in lymphoid malignancies and some autoimmune diseases such as diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Sjögren syndrome.


Assuntos
Doenças Autoimunes/diagnóstico , Neoplasias Hematológicas/diagnóstico , Cadeias Leves de Imunoglobulina/sangue , Paraproteinemias/diagnóstico , Testes Sorológicos , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Diagnóstico Diferencial , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/imunologia , Humanos , Cadeias Leves de Imunoglobulina/análise , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Paraproteinemias/sangue , Paraproteinemias/imunologia , Valor Preditivo dos Testes , Prognóstico , Testes Sorológicos/métodos , Testes Sorológicos/normas
9.
Clin Adv Hematol Oncol ; 17(7): 405-411, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31449507

RESUMO

The BCR-ABL1-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, can evolve into a form of secondary acute myeloid leukemia termed MPN in blast phase (MPN-BP). MPN in accelerated phase (MPN-AP), which is defined by 10% to 19% myeloid blasts in the peripheral blood or bone marrow, is a precursor to MPN-BP. Alternative definitions of MPN-AP exist based on studies identifying clinical variables that portend a poor prognosis and high risk for progression to MPN-BP. Allogeneic hematopoietic stem cell transplant remains the only curative therapeutic option; however, advanced age and high comorbidity index preclude the majority of patients from receiving this treatment modality. This article reviews management considerations for the advanced-phase MPNs (MPN-AP and MPN-BP), with a special focus on MPN-AP, and highlights novel experimental therapies.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transtornos Mieloproliferativos , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Humanos , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia
10.
Asian Pac J Cancer Prev ; 20(7): 2109-2115, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350973

RESUMO

Background: Gas station workers are exposed to carcinogenic substances with impact on the hematologic and immune systems. The aim was to apply the immunophenotyping as a tool in the biological monitoring. Methods: This is a workplace-based case-control study with 49 workers and 26 controls. Medical interviews, hematological exams, and immunophenotyping analyses were performed. According to risk behavior (cleaning flannel and mistrust in the automatic fuel supply) the workers were divided into two groups: low risk (group 1) and high risk (group 2). Results: The results showed that CD16, HLA-DR, CD25, CD56+, CD16 CD56 low, and CD56 high expressions were higher in workers when compared to the control group (P =0.020, P =0.001, P =0.001; P =0.034, P=0.023, and P =0.008, respectively). The expressions of CD2, CD8, CD10, CD8low, and CD4/CD8 ratios were lower (P =0.016, P =0.001, P=0.001, P= 0.017, P = 0.0259, and P =0.029, respectively). Headache and paresthesia complaints were associated with workers when compared to the control group (OR = 4.091, 95% CI, 1.400 -11.951, P = 0.014; OR =12.12, 95% CI, 1.505 - 97.61, P =0.004). Using cleaning flannel and mistrust in the automatic fuel supply (risk behaviors) were associated with group 2 (OR = 9.71, 95% CI, 2.60-36.26, P = 0.005; OR = 18.18, 95% CI, 2.04-161.37, P = 0.004). Conclusions: The results strengthen the worker's immunosuppression hypothesis, which may contribute to some disorders and the carcinogenesis process. The evaluation of the immune system by flow cytometry is a promising tool for monitoring blood malignancy risk in addition to regular classic hematological exams.


Assuntos
Biomarcadores Tumorais/análise , Gasolina/efeitos adversos , Neoplasias Hematológicas/diagnóstico , Imunidade Celular/imunologia , Imunofenotipagem/métodos , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Antígenos CD/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Antígenos HLA/metabolismo , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/etiologia , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Doenças Profissionais/sangue , Doenças Profissionais/etiologia , Prognóstico , Subpopulações de Linfócitos T/imunologia
12.
Curr Med Sci ; 39(4): 546-550, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346989

RESUMO

In this study, we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies. A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology, Union Hospital, between Apr. 2014 and Dec. 2014 were enrolled in this study. There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC. The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System, and they were divided into four subgroups [score ≤3 (n=35), score=4 (n=37), score=5 (n=47), and score ≥6 (n=12)] according to ISTH scores. Using 28-day mortality as the endpoint, the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20). The results showed that the plasma factor V activity was significantly weaker, and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01). The factor V activity, peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01). Among factor V activity, lag time, peak, ETP, and ttPeak, only the factor V activity was significantly decreased in the non-survival subgroup compared with the survival subgroup (P<0.01). With the increase in ISTH score, the ETP and peak decreased gradually. The binary logistic regression analysis revealed that PLT, D-dimer, factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System. Using DIC diagnosed by ISTH Integral System as the endpoint, the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT). In conclusion, factor V activity, ETP and peak had diagnostic value for DIC in patients with hematological malignancies, and only factor V activity had limited prognostic value.


Assuntos
Coagulação Intravascular Disseminada/sangue , Fator V/metabolismo , Neoplasias Hematológicas/sangue , Prognóstico , Adulto , Testes de Coagulação Sanguínea , Coagulação Intravascular Disseminada/patologia , Feminino , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Curva ROC , Trombina/metabolismo , Trombose/sangue , Trombose/genética , Trombose/patologia
13.
Ann Hematol ; 98(9): 2163-2177, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243569

RESUMO

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas , Herpesvirus Humano 4/metabolismo , Transtornos Linfoproliferativos , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Humanos , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Irmãos , Taxa de Sobrevida
14.
Int J Lab Hematol ; 41 Suppl 1: 131-141, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31069978

RESUMO

Advances in molecular genetic sequencing techniques have contributed to the elucidation of previously unknown germline mutations responsible for inherited thrombocytopenia (IT). Regardless of age of presentation and severity of symptoms related to thrombocytopenia and/or platelet dysfunction, a subset of patients with IT are at increased risk of developing myeloid neoplasms during their life time, particularly those with germline autosomal dominant mutations in RUNX1, ANKRD26, and ETV6. Patients may present with isolated thrombocytopenia and megakaryocytic dysmorphia or atypia on baseline bone marrow evaluation, without constituting myelodysplasia (MDS). Bone marrow features may overlap with idiopathic thrombocytopenic purpura (ITP) or sporadic MDS leading to misdiagnosis. Progression to myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML) may be accompanied by progressive bi- or pancytopenia, multilineage dysplasia, increased blasts, cytogenetic abnormalities, acquisition of bi-allelic mutations in the underlying gene with germline mutation, or additional somatic mutations in genes associated with myeloid malignancy. A subset of patients may present with MDS/AML at a young age, underscoring the growing concern for evaluating young patients with MDS/AML for germline mutations predisposing to myeloid neoplasm. Early recognition of germline mutation and predisposition to myeloid malignancy permits appropriate treatment, adequate monitoring for disease progression, proper donor selection for hematopoietic stem cell transplantation, as well as genetic counseling of the affected patients and their family members. Herein, we describe the clinical and diagnostic features of IT with germline mutations predisposing to myeloid neoplasms focusing on mutations involving RUNX1, ANKRD26, and ETV6.


Assuntos
Doenças Genéticas Inatas , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Proteínas de Neoplasias , Trombocitopenia , Aloenxertos , Genes Dominantes , Aconselhamento Genético , Doenças Genéticas Inatas/sangue , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/terapia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Trombocitopenia/terapia
15.
Transfus Apher Sci ; 58(3): 326-331, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31047824

RESUMO

BACKGROUND: removal of incompatible red blood cells (RBCs) or plasma is usually required to avoid hemolysis during infusion of ABO incompatible bone marrow (BM) allogeneic transplants. This process often involves separation of buffy coat (BC) by centrifugation in automated devices. We have evaluated the Spectra Optia™ (Optia) apheresis system to determine its effectiveness in BC concentration, volume reduction and RBCs depletion of ABO-incompatible BM compared with our previous method using Cobe Spectra™ (Cobe). MATERIALS AND METHODS: 28 processes were performed with Optia and 52 with Cobe. We compared volume reduction, RBCs depletion, and recovery of total nucleated cells (TNCs), mononuclear cells (MNCs), CD34+ and CD3+ cells in the final product. Hematopoietic engraftment was ascertained. We used Saphiro-Wilks and Kolmorgorov- Smirnov tests to test normality and Mann-Whitney's U test to compare means between both groups. RESULTS: We found statistically significant differences favoring Optia versus Cobe in TNCs recovery (62% vs. 37%), CD34+ cell recovery (98 vs 84%), volume reduction (91 vs 84%), and RBCs depletion (99 vs. 97%), but not in processing time or time to engraftment. CONCLUSION: Optia achieves high RBCs and volume depletion of BM, while providing excellent CD34+ recovery in clinical routine. Some parameters compare favorably with Cobe Spectra.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Remoção de Componentes Sanguíneos , Transplante de Medula Óssea , Sobrevivência de Enxerto , Doadores de Tecidos , Aloenxertos , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Humanos , Masculino
16.
Pediatr Hematol Oncol ; 36(3): 161-172, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31037986

RESUMO

Human adenovirus (HAdV) is recognized as a serious pathogen after allogeneic hematopoietic stem cell transplantation (HSCT), causing morbidity and mortality. Currently, there is no universal agreement regarding routine HAdV surveillance after HSCT. We assessed the impact of HAdV weekly monitoring by polymerase chain reaction (PCR) on HAdV viremia rates and the risk factors that influence survival. Three-hundred and fifty-six pediatric allogeneic HSCT were done between 2007 and 2015. Until July 2011, HAdV testing was performed based on clinical suspicion (cohort 1, n = 175) and from August 2011, weekly blood-HAdV monitoring was done (cohort 2, n = 181) until day +100. Twenty-three patients (4 [2.3%] from cohort 1 and 19 [10.5%] from cohort 2, p = .001) were found with HAdV viremia and seven of them died. Both cohorts had a similar incidence of HAdV-associated mortality (3/175; 1.7% in cohort 1 and 4/181; 2.2% in cohort 2). Respiratory failure was the cause of death in all patients. Clinical symptoms appeared prior to or within 5 days of HAdV detection in cohort 2. In summary, weekly monitoring was associated with higher detection of HAdV. The study could not assess survival benefit due to small numbers of HAdV-positive cases. In many instances, symptoms occurred with the development of positive HAdV blood PCR results and hence, symptomatology could have triggered the test. Future studies are needed to provide data that help establishing a uniform approach for regular monitoring of HAdV post-transplant.


Assuntos
Infecções por Adenoviridae , Adenovírus Humanos , DNA Viral , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Infecções por Adenoviridae/sangue , Infecções por Adenoviridae/genética , Infecções por Adenoviridae/mortalidade , Adenovírus Humanos/genética , Adenovírus Humanos/metabolismo , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , DNA Viral/sangue , DNA Viral/genética , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Fatores de Risco , Viremia/sangue , Viremia/genética , Viremia/mortalidade
17.
Pediatr Blood Cancer ; 66(8): e27797, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31099154

RESUMO

BACKGROUND: Asparaginase is a critical component of lymphoblastic leukemia therapy, with intravenous pegaspargase (PEG) as the current standard product. Acute adverse events (aAEs) during PEG infusion are difficult to interpret, representing a mix of drug-inactivating hypersensitivity and noninactivating reactions. Asparaginase Erwinia chrysanthemi (ERW) is approved for PEG hypersensitivity, but is less convenient, more expensive, and yields lower serum asparaginase activity (SAA). We began a policy of universal premedication and SAA testing for PEG, hypothesizing this would reduce aAEs and unnecessary drug substitutions. PROCEDURE: Retrospective chart review of patients receiving asparaginase before and after universal premedication before PEG was conducted, with SAA performed 1 week later. We excluded patients who had nonallergic asparaginase AEs. Primary end point was substitution to ERW. Secondary end points included aAEs, SAA testing, and cost. RESULTS: We substituted to ERW in 21 of 122 (17.2%) patients pre-policy, and 5 of 68 (7.4%) post-policy (RR, 0.427; 95% CI, 0.27-0.69, P = 0.028). All completed doses of PEG yielded excellent SAA (mean, 0.90 units/mL), compared with ERW (mean, 0.15 units/mL). PEG inactivation post-policy was seen in 2 of 68 (2.9%), one silent and one with breakthrough aAE. The rate of aAEs pre/post-policy was 17.2% versus 5.9% (RR, 0.342; 95% CI, 0.20-0.58, P = 0.017). Grade 4 aAE rate pre/post-policy was 15% versus 0%. Cost analysis predicts $125 779 drug savings alone per substitution prevented ($12 402/premedicated patient). CONCLUSIONS: Universal premedication reduced substitutions to ERW and aAE rate. SAA testing demonstrated low rates of silent inactivation, and higher SAA for PEG. A substantial savings was achieved. We propose universal premedication for PEG be standard of care.


Assuntos
Antineoplásicos/administração & dosagem , Asparaginase/administração & dosagem , Hipersensibilidade a Drogas/prevenção & controle , Monitoramento de Medicamentos/métodos , Substituição de Medicamentos/normas , Neoplasias Hematológicas/tratamento farmacológico , Pré-Medicação/estatística & dados numéricos , Administração Intravenosa , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Asparaginase/efeitos adversos , Asparaginase/farmacocinética , Criança , Pré-Escolar , Feminino , Seguimentos , Neoplasias Hematológicas/sangue , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Distribuição Tecidual , Adulto Jovem
18.
Ann Biol Clin (Paris) ; 77(3): 281-286, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31115339

RESUMO

Extreme leukocytosis may lead to false hyperkalemia when blood samples are conveyed by pneumatic tube system (PTS). The aim of this study was to define whether even moderate leukocytosis and also non malignancy cells like neutrophils may influence potassium values after PTS transportation. MATERIALS AND METHODS: Uncentrifuged blood samples are sent to the local laboratory through PTS. Data were retrospectively collected from routine testing carried out on all specimens arrived in the laboratory between September 2017 and March 2018. Clinical chemistry testing is routinely performed using lithium-heparin tubes. When false hyperkalemia induced by leukocytosis is suspected, potassium measurement is then performed in serum (clotting activator tubes) or whole blood samples. The analysis was focused on samples with both leukocytosis (i.e., >15×109/L) and plasma potassium >5.0 mmol/L, before any corrective therapeutic measure to lower potassium levels was established. RESULTS: A total number of 18 samples were included in our analysis, 9 drawn from patients with hematologic malignancies and 9 without. In the 9 patients without hematologic malignancies (median leukocyte count, 20.4×109/L), the median potassium value was 5.4 mmol/L in plasma and 4.5 mmol/L in serum or whole blood. In the 9 patients with hematologic malignancies (median leukocyte count, 151.9×109/L; p <0.001), the median potassium value was 7.7 mmol/L in plasma and 4.3 mmol/L in serum or whole blood (median difference, 2.9 mmol/L; p <0.001). CONCLUSION: The results of our study suggest that even modest leukocytosis (i.e., around 15x109/L), which can be frequently encountered in clinical practice, may be associated with a significant variation of plasma potassium. This would lead us to conclude that plasma samples transportation by PTS should be avoided in patients with even mild leukocytosis.


Assuntos
Coleta de Amostras Sanguíneas/efeitos adversos , Ar Comprimido/efeitos adversos , Hiperpotassemia/diagnóstico , Leucocitose/diagnóstico , Fase Pré-Analítica/métodos , Transportes/métodos , Artefatos , Coleta de Amostras Sanguíneas/métodos , Estudos de Casos e Controles , Diagnóstico Diferencial , Reações Falso-Positivas , Neoplasias Hematológicas/sangue , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/etiologia , Inflamação/sangue , Leucocitose/sangue , Leucocitose/etiologia , Potássio/análise , Potássio/sangue , Fase Pré-Analítica/normas , Estudos Retrospectivos , Transportes/normas
19.
Exp Hematol ; 74: 25-32.e1, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31078634

RESUMO

Lipocalin-2 (LCN2) is an immunomodulatory protein holding major metabolic and immune functions. It is involved in several inflammatory processes and induced by cytokines of the interleukin-1 family known as contributors to the morbidity in graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). The possible role of LCN2 in predicting outcome and course of illness has never been elucidated in patients undergoing HSCT for hematologic malignancies. We conducted a prospective cohort study including 40 patients following autologous or allogeneic HSCT by collecting plasma samples at seven time points with respect to GVHD, relapse, and outcome. LCN2 levels were significantly increased in acute patients with GVHD compared with autologous and healthy controls (125.7 ng/mL vs. 65.9 and 71.4 ng/mL) and correlated with its severity. Similarly, LCN2 levels were significantly elevated in chronic GHVD compared with autologous and healthy controls (295.0 ng/mL vs. 54.9 and 76.5 ng/mL). Moreover, LCN2 correlated with mortality. The suspected role of LCN2 as a predictive parameter for outcome and prognosis needs to be further investigated.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Lipocalina-2/sangue , Doença Aguda , Adulto , Aloenxertos , Autoenxertos , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
20.
Acta Haematol ; 141(4): 245-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30965330

RESUMO

BACKGROUND: The incidence of venous thromboembolism (VTE) in haematological malignancies varies according to the type and grade of the disease and clinical variables, and there is a need to develop a tool to predict the occurrence of VTE in cancer patients at diagnosis to tailor prophylactic anticoagulation use during treatment. OBJECTIVE: To study the incidence of VTE in haematological malignancies and clarify whether vascular and inflammatory biomarkers could be used as predictors of VTE in those patients. METHODS: This was a prospective observational cohort study. Hypercoagulability and inflammatory biomarkers were assayed in a group of 171 patients with haematological malignancies at diagnosis. These markers included (1) coagulation and fibrinolysis activation markers (D-dimer, fibrinogen, antithrombin, plasminogen activator inhibitor 1), (2) endothelial and platelet activation markers (von Willebrand factor and soluble P-selectin), and (3) inflammatory markers (tumour necrosis factor αand interleukin 6). The end point was mortality or symptomatic VTE. RESULTS/CONCLUSION: The incidence of symptomatic VTE was 7%. None of the tested biomarkers showed statistical significance as predictors for the occurrence of VTE in haematological malignancies. However, there were statistically significant associations between the occurrence of VTE and central venous access device insertion, the prothrombin time, and the erythrocyte sedimentation rate. An ESR above 106.5 mm/h is associated with increased VTE occurrence.


Assuntos
Fibrinólise , Neoplasias Hematológicas/sangue , Ativação Plaquetária , Tromboembolia/sangue , Biomarcadores/sangue , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Inflamação/sangue , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboembolia/epidemiologia , Tromboembolia/etiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA