Flow cytometric quantification of phagocytosis in acute myeloid leukemia

Phagocytosis was studied by flow cytometry (FCM) in 15 patients with acute myeloid leukemia (AML). The pattern of phagocytosis differed markedly between AML and controls. The percentage of phagocytosing AML leukocytes was below that of the controls (p < 0.01). The phagocytic capacity of a subpopulation of leukemic cells was diminished, but compensated by the phagocytosis of a few prey by each of many immature leukocytes. Phagocytosis by immature and mature AML leukocytes was receptor dependent, and both carried functional complement receptors. Attachment to the cell surface was not rate-limiting in phagocytosing AML leukocytes.     

The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a prognostic score

In acute myeloid leukemia (AML) patients, a variety of clinical and biologic parameters, including phenotype, have been examined for potential value in predicting treatment response and survival. The European Group for the Immunological Classification of Leukaemias (EGIL) has proposed that AML be defined immunologically by the expression of 2 or more of the following myeloid markers: myeloperoxidase, CD13, CD33, CDw65, and CD117. With regard to this classification, the prognostic significance of 21 antigens taken separately and with immunophenotypic subgroups were evaluated and compared with other clinical and biological variables in 177 adult AML patients. None of the antigens tested were associated with treatment outcome. In contrast, patients with blasts disclosing a full expression of panmyeloid phenotype (defined by the expression of all 5 myeloid markers) had a higher complete remission rate (P <. 0001) and differed significantly in disease-free survival (P =.02) and overall survival (P =.008) than patients whose cells expressed fewer than 5 of these markers. In multivariate analysis, only age, panmyeloid phenotype, performance status, and permeability glycoprotein activity influence treatment outcome. Cytogenetics was significant in univariate analysis but not in multivariate analysis, most likely because of the redundancy with panmyeloid phenotype and a higher sensitivity of immunophenotyping. Patients whose cells exhibit the panmyeloid phenotype appear to define a relatively homogeneous biological subset of AML. The 4 independent prognostic factors were used to create a prognostic score, defined by the number of factors present. This score permitted a stratification of patients with AML, thereby allowing for the consideration of innovative therapies to improve outcome in the poorer outcome groups.     

CD25 as an adverse prognostic factor in elderly patients with acute myeloid leukemia

Objectives: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated.

Methods: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry.

Results: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML. CD25 positivity was significantly correlated with an inferior complete remission (CR), event-free survival (EFS), and overall survival. Multivariate analysis showed CD25 positivity to be a significant prognostic predictor of CR and EFS. A regimen of low-dose cytarabine and aclarubicin combined with granulocyte-colony-stimulating factor (CAG) led to higher CR rates in the CD25-positive AML patients than intensive chemotherapies. CD25 expression was increased at relapse and in the development of leukemic status from myelodysplastic syndrome or myeloproliferative neoplasm.

Discussion: An effective treatment strategy for elderly patients with CD25-positive AML has not been established. Further studies are needed to evaluate the effect of a CAG regimen and allogenic stem cell transplantation in patients.

Conclusion: CD25 is an independent prognostic factor in elderly AML patients. Alternative therapies for CD25-positive elderly AML patients are needed.     

The prognostic value of hematogones in patients with acute myeloid leukemia

In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B‐lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse‐free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 ? 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 ? 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk‐adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566–570, 2016. © 2016 Wiley Periodicals, Inc.     

急性髓系白血病患者预后分组方式的探讨

目的 评价原发、初治急性髓系白血病(AML)患者诱导治疗后不同时间骨髓幼稚细胞比例对预后的影响.将细胞遗传学与诱导治疗后不同时间骨髓幼稚细胞比例相结合,提出新的AML患者预后分组方法.方法 回顾性分析1999年1月1日至2008年2月1日于我院住院的原发、初治AML患者(非M3型)105例,所有患者在诱导化疗结束时(T1)和(或)骨髓抑制期(T2)进行骨髓穿刺检查.有细胞遗传学资料的患者97例.结果 (1)T1或T2时间点105例行骨髓穿刺检查的患者,骨髓幼稚细胞<0.05者和≥0.05者相比,T1时间点完全缓解(CR)率分别为86.0%、47.4%,3年无复发生存(RFS)率分别为46.2%、21.6%,3年总生存率分别为49.7%、25.6%.T2时间点二者CR率分别为86.3%、41.4%,3年RFS率分别为52.4%、18.9%,3年总生存率分别为61.1%、35.2%,差异均有统计学意义.且T1和,12时间点骨髓幼稚细胞比例具有相关性.(2)将染色体核型预后中等组患者根据T1或T2时间点骨髓幼稚细胞比例分为二组:骨髓幼稚细胞<0.05者和≥0.05者.前者预后与良好组相近,后者预后与不良组相近.(3)多因素分析表明T1或12时间点骨髓幼稚细胞比例是AML患者的独立预后因素.T1时间点骨髓幼稚细胞比例可能较T2时间点骨髓幼稚细胞比例意义更大.结论 以0.05为界,T1或T2时间点骨髓幼稚细胞比例是原发、初治AML患者(非M3型)CR率、RFS、总生存的独立预后因素.将染色体核型与T1和(或)T2时间点骨髓幼稚细胞比例相结合分组,可进一步区分中等组患者,有助于评估预后和选择治疗方案.     

Flow cytometric quantification and immunophenotyping of leukemic stem cells in acute myeloid leukemia

Leukemic stem cells (LSCs) are root of clonal growth in acute myeloid leukemia (AML) and responsible for the propagation of leukemic blasts (LBs). LSCs are considered as CD34?+?CD38- population among LBs and often express as CD123, CD44, or CD184, which are rarely expressed on normal hematopoietic stem cells and could be the potential therapeutic targets. Using multi-color flow cytometry, we analyzed the proportions of CD34?+?CD38- LSCs and expression of CD123, CD44, and CD184 on LSCs in 63 patients with AML. The median proportion of LSCs was 1.3?% (0.0-33.1?%) at the time of diagnosis. Of all patients, 74.6?% of them had CD123-positive LSCs, all patients had CD44-positive LSCs, and 85.7?% had CD184-positive LSCs, respectively. The proportions of LSCs were significantly lower in the complete remission (CR) group compared with non-CR group (P?=?0.006). The lower proportions of LSCs in CR group indicated that measurement of the proportion of LSCs might be helpful to predict the prognosis of AML.     

Multidrug resistance as a potential prognostic indicator in acute myeloid leukemia with normal karyotypes

INTRODUCTION: Approximately 45% of adults with acute myeloid leukemia (AML) have normal karyotypes and therefore lack structural abnormalities that can assist in the localization and characterization of molecular defects. The current study attempted to evaluate the potential prognostic role of multidrug resistance (MDR), regarded as one of the potential prognostic factors for the outcome of overall AML, for AML with normal karyotypes. METHOD AND MATERIALS: A functional MDR assay was performed in pretreatment samples from AML patients with normal karyotypes. The complete remission (CR) rate, event-free survival (EFS), and overall survival (OS) were analyzed according to the MDR status and clinical prognostic factors for 88 patients with AML with normal karyotypes. RESULTS: MDR by efflux was expressed in 14 out of 48 evaluable patients (29%) but failed to identify the association with CR (p = 0.124). However, MDR was identified as an independent prognostic factor for EFS and OS (p = 0.013 and 0.046) together with the use of stem cell transplantation (p = 0.009 for EFS and 0.029 for OS) and the WBC count at presentation (p = 0.023 for EFS and 0.034 for OS). CONCLUSION: The functional MDR assay may provide information on the prognosis of AML patients with normal karyotypes, and it might be a possible guideline for risk-stratified treatment strategies in AML with normal karyotypes.     

Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients

Osteopontin (OPN) is a glycoprotein that is secreted by osteoblasts and hematopoietic cells. OPN suppresses the proliferation of hematopoietic stem cells in vitro and may regulate the hematopoietic stem cell pool. Increased serum OPN concentrations occur in chronic myeloid leukemia, multiple myeloma, and acute myeloid leukemia (AML). In the present study, we analyzed the prognostic impact of OPN in AML by investigating the expression and relevance of OPN in newly diagnosed AML patients from 2 large study groups (the German AML Cooperative Group and the Dutch-Belgian Hematology Oncology Cooperative group). IHC (n = 84), ELISAs of blood/BM sera (n = 41), and microarray data for mRNA levels (n = 261) were performed. Expression of OPN protein was increased in AML patients both in BM blasts (IHC) and in BM serum (ELISA) compared with healthy controls. Patients expressing high levels of OPN within the BM (IHC) experienced shortened overall survival (OS; P = .025). Multivariate analysis identified karyotype, blast clearance (day 16), and the level of OPN expression as independent prognostic factors for OS. This prompted us to analyze microarray data from 261 patients from a third cohort. The analysis confirmed OPN as a prognostic marker. In summary, high OPN mRNA expression indicated decreased event-free survival (P = .0002) and OS (P = .001). The prognostic role of OPN was most prominent in intermediate-risk AML. These data provide evidence that OPN expression is an independent prognostic factor in AML.     

Older patients with acute myeloid leukemia

Outcomes for older patients with acute myeloid leukemia have not improved over the last three decades, with only a small proportion of patients achieving long-term disease-free survival with standard induction chemotherapy. Older patients are more likely to have comorbidities, diminished functional reserve and other age-related issues, which decrease their tolerability to chemotherapy. Furthermore, the disease is frequently associated with poor-risk features, such as unfavorable cytogenetic abnormalities, antecedent hematologic disorders and expression of the multidrug resistant P-glycoprotein, which are associated with chemoresistant disease. Therefore, is it not only important to develop newer treatment modalities, but also to develop and validate prognostic models to help select the patients who are likely to benefit from and be suitable for intensive therapy, and reproducibly risk-stratify (based on disease biology) a relatively uniform group of older patients onto trials, so that the clinical significance of new therapeutic agents can be evaluated.     

Clinically useful prognostic factors in acute myeloid leukemia

The clinical outcome of acute myeloid leukemia (AML) is extremely variable, ranging from survival of a few days to cure. Different clinical and biological features at diagnosis have been reported as useful for the prediction of clinical outcome; however, in most AML cases induction therapy must be initiated as soon as possible, therefore, the possibility of stratifying patients at diagnosis is generally not taken into account, with the exception of acute promyelocytic leukemia in which morphology, immunophenotype, and molecular biology allow a rapid diagnosis and the adoption of specific therapy. As a consequence, prognostic factors in AML are more useful for the prediction of relapse, rather than for the stratification of induction therapy. Most relevant studies, based on large multicenter trials have definitively demonstrated that age and cytogenetics at diagnosis are the most important prognostic determinants for patients with AML. Early blast clearance after induction chemotherapy represents a further important factor of potential utility into clinical practice. Finally, biologic parameters, such as mutations of FLT3 and nucleophosmin, have been reported as useful for the prognostic categorization mainly in patients with intermediate cytogenetics and can also represent potential targets for new therapeutic agents.     

Clinical and prognostic values of TP53 mutation in patients with acute myeloid leukemia

正Objective To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML).Methods A retrospective analysis of265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was     

Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia

To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)-ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.