Normal variation of bone marrow B-cell precursors according to age - reference ranges for studies in myelodysplastic syndromes in Brazil.

BACKGROUND: Normal B lymphoid maturation occurs in bone marrow (BM) throughout life, but immature B-cell progenitors (BCPs) are more numerous in children than in adults. To assess the normal values according to age became important as BCPs are decreased in myelodysplastic syndromes and have been considered an important diagnostic and prognostic feature in these clonal disorders. METHODS: in a multicenter retrospective study from the Brazilian Group of Flow Cytometry we analyzed the variation of BCPs in normal BM according to age and technical peculiarities of each laboratory. We analysed of 45 BM donors and 89 cases examined for elucidation of transitory reactive cytopenias presenting a normal BM immunophenotyping. BCPs were enumerated as CD19+ /CD34+ /CD45dim /CD10+ cells (panel 1) or CD19+ /CD34+ /CD45dim cells (panel 2) among the total nucleated non-erythroid cells and as percentage of CD34+ cells. RESULTS: we included 134 cases. Panel 1 was applied in 88 cases and panel 2 was used in 46. Age range: 10 months to 89 years. In a multiple regression, % BCPs/total nucleated cells was an exponential function of age. Age explained alone 49.4% of the variance, while 'panel used' explained 1.8% and 'laboratory' explained 0.7%. Age explained only 24.9% of the variance of BCPs/CD34+ cells. CONCLUSIONS: in normal individuals, BM B-cell precursors varied mainly according to age, but were also dependent on technical peculiarities of operators and equipments. Analysis by phenotype and as percentage of total nucleated cells was more accurate and less susceptible to variation than evaluating % BCPs/total CD34+ cells. © 2017 International Clinical Cytometry Society.

Role of new Immunophenotypic Markers on Prognostic and Overall Survival of Acute Myeloid Leukemia: a Systematic Review and Meta-Analysis.

Despite technological advances, the prognosis and survival of acute myeloid leukemia (AML) adult patients remain low, compared with other hematologic malignancies. Some antigens detected by immunophenotyping may soon play a significant role in the pathophysiologic, prognostic, and overall survival (OS) rate of AML patients. Therefore, we conducted a systematic review and meta-analysis of PubMed, Scopus, Science Direct, Web of Science, and the Cochrane Library (using PRISMA guidelines). We analyzed 11 studies and 13 antigens, detected through the immunophenotyping of 639 patients. From them, twelve exhibited a negative impact with AML prognosis. The meta-analysis demonstrated a high expression of AML markers, which have been associated with a decrease in survival over 10 months (RR 2.55; IC 95%; 1.49-4.37) and over 20 months (RR 2.46; IC 95%; 1.75-3.45). Knowing that the expression of immunophenotypic markers, which are not used on a routine basis, might be able to influence disease behavior, looks promising. However, they have been associated with a poor prognosis as well as a decrease in survival. This may allow for different chemotherapeutical protocols, including future studies for new therapeutic targets.

Frequency of polycythemia in individuals with normal complete blood cell counts according to the new 2016 WHO classification of myeloid neoplasms.

INTRODUCTION: Polycythemia vera (PV) is a disorder characterized by clonal proliferation of myeloid cells and increased red blood cell mass. Recently, the revised 2016 WHO classification of myeloid neoplasms decreased the threshold levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new proposed cutoffs have remarkable overlap with the normal reference values reported and the clinical impact of these new cutoffs has not been widely assessed in the general population. METHODS: We retrospectively examined 248 839 patients with presumptively normal complete blood cell results, consecutively obtained in an outpatient setting. RESULTS: The proportion of men with Hb >165 g/L was 5.99%, Hct>49% was 2.4%, and Hb >165 g/dL or Hct>49% was 6.48%, while the proportion of women with Hb >160 g/L was 0.22%, Hct>48% was 0.11%, and Hb >160 g/L or Hct>48% was 0.28%. CONCLUSION: The isolated use of the proposed Hb/Hct levels as a definer of polycythemia may lead to a substantial increase in unnecessary diagnostic tests. In cases with borderline levels of hemoglobin, the diagnostic workup of PV should only be indicated in the presence of clinical and/or laboratorial features associated with MPN.

Diagnosis of chronic lymphoproliferative disorders by flow cytometry using four-color combinations for immunophenotyping: A proposal of the brazilian group of flow cytometry (GBCFLUX).

BACKGROUND: Multiparametric flow cytometry (MFC) is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purposes of the Brazilian Group of Flow Cytometry (GBCFLUX), the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country. Most laboratories in Brazil work with 4-fluorescence flow cytometers, which is why the GBCFLUX CLPD Committee has proposed 4-color monoclonal antibody (MoAb) panels. METHODS/RESULTS: Panels for screening and diagnosis in B, T and NK lymphoproliferative disorders were developed based on the normal differentiation pathways of these cells and the most frequent phenotypic aberrations. Important markers for prognosis and for minimal residual disease (MRD) evaluation were also included. The MoAb panels presented here were designed based on the diagnostic expertise of the participating laboratories and an extensive literature review. CONCLUSION: The 4-color panels presented to aid in the diagnosis of lymphoproliferative neoplasms by GBCFLUX aim to provide clinical laboratories with a systematic, step-wise, cost-effective, and reproducible approach to obtain an accurate immunophenotypic diagnosis of the most frequent of these disorders. © 2016 International Clinical Cytometry Society.

Does soy increase blood counts in myelodysplastic syndromes? / Será que a soja aumenta as contagens sanguíneas em síndrome mielodisplásica?

Myelodysplastic syndromes (MDS) are a group of clonal stem cell diseases characterized by ineffective hematopoiesis, bone marrow hyperproliferation, cytopenias in peripheral blood and risk of transformation into acute leukemia. We decided to investigate the effects of a soy concentrate on MDS patients based on the follow-up results of a 61 year-old Japanese female patient who was diagnosed with MDS and refractory cytopenia with multilineage dysplasia in 2003 (hemoglobin = 11g/dL; white blood cells count = 2,500/uL and platelets = 25,000/uL; marrow with mild dysplasia and normal karyotype; paroxysmal nocturnal hemoglobinuria was excluded). She started using soy as a dietary supplementation in May 2004 and presented a gradual increment in blood counts, achieving normalization approximately eight months afterwards. Among the soy components, the main compounds with anti-carcinogenic activity are the isoflavones (genistein and daidzein). Based on these lines of evidence, we proposed to administer daily a standard soy concentrate to 14 MDS out-patients for a minimum period of three months and maximum of 12 months, in an attempt to evaluate prospectively the possible increase in hemoglobin, neutrophils and platelet counts. A historical control group was used to compare results. The use of a soy concentrate in a standardized manner was associated with an increase in neutrophil and/or platelet counts in some cases, but spontaneous increments were also observed in historical controls. This preliminary study does not allow establishing a relation between soy supplementation and blood cell count increase.

As síndromes mielodisplásicas (SMD) são um grupo das doenças clonais de células-tronco caracterizado por hematopoese ineficaz, hiperproliferação de medula óssea, citopenias no sangue periférico e risco de transformação para leucemia aguda. Decidimos investigar os efeitos de um concentrado de soja em pacientes com SMD com base no fato de termos o seguimento de uma paciente japonesa, de 61 anos de idade, que foi diagnosticada em 2003 com SMD, citopenia refratária com displasia subtipo multilinhagens (hemoglobina = 11 g/dL; contagem de glóbulos brancos = 2.500/uL e plaquetas = 25.000/uL; medula com displasia leve e cariótipo normal; hemoglobinúria paroxística excluída), e que começou a usar a soja como suplemento alimentar em maio de 2004, apresentando gradual aumento da contagem das células sanguíneas, atingindo a normalização cerca de oito meses depois. Entre os componentes da soja, os principais compostos com propriedades anticarcinogênese são as isoflavonas (Ge nisteína e daidzeína). Com base nessas linhas de evidência, foi proposto oferecer diariamente um concentrado de soja padrão, por um período mínimo de três meses e máximo de doze meses, a 14 pacientes ambulatoriais, na tentativa de avaliar, prospectivamente, o possível aumento de hemoglobina, neutrófilos e plaquetas. Um grupo controle histórico foi utilizado para comparar os resultados. O uso de um concentrado de soja de forma padronizada foi associado ao aumento na contagem de neutrófilos e/ou de plaquetas em alguns casos, mas aumentos espontâneos também foram observados em controles históricos. Este estudo preliminar não permite estabelecer relação entre o uso de soja e o aumento na contagem sanguínea.