scholarly journals Integrating clinical features with genetic factors enhances survival prediction for adults with acute myeloid leukemia

2020 ◽  
Vol 4 (10) ◽  
pp. 2339-2350 ◽  
Author(s):  
Douglas R. A. Silveira ◽  
Lynn Quek ◽  
Itamar S. Santos ◽  
Anna Corby ◽  
Juan L. Coelho-Silva ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Sao Paulo ◽  
Survival Prediction ◽  
São Paulo ◽  
Data Set ◽  
Significant Difference ◽  
De Medicina ◽  
Acute Myeloid

Abstract The 2017 European LeukemiaNet 2017 acute myeloid leukemia (AML) risk stratification (ELN2017) is widely used for risk-stratifying patients with AML. However, its applicability in low- and middle-income countries is limited because of a lack of full cytogenetic and molecular information at diagnosis. Here, we propose an alternative for risk stratification (the Adapted Genetic Risk [AGR]), which permits cytogenetic or molecular missing data while retaining prognostic power. We first analyzed 167 intensively treated patients with nonacute promyelocytic leukemia AML enrolled in São Paulo, Brazil (Faculdade de Medicina da Universidade de São Paulo), as our training data set, using ELN2017 as the standard for comparison with our AGR. Next, we combined our AGR with clinical prognostic parameters found in a Cox proportional hazards model to create a novel scoring system (survival AML score, SAMLS) that stratifies patients with newly diagnosed AML. Finally, we have used 2 independent test cohorts, Faculdade de Medicina de Ribeirão Preto (FMRP; Brazil, n = 145) and Oxford University Hospitals (OUH; United Kingdom, n = 157) for validating our findings. AGR was statistically significant for overall survival (OS) in both test cohorts (FMRP, P = .037; OUH, P = .012) and disease-free survival in FMRP (P = .04). The clinical prognostic features in SAMLS were age (>45 years), white blood cell count (<1.5 or >30.0 × 103/μL), and low albumin levels (<3.8 g/dL), which were associated with worse OS in all 3 cohorts. SAMLS showed a significant difference in OS in the training cohort (P < .001) and test cohorts (FMRP, P = .0018; OUH, P < .001). Therefore, SAMLS, which incorporates the novel AGR evaluation with clinical parameters, is an accurate tool for AML risk assessment.

scholarly journals Prevalence of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD+) in de novo acute myeloid leukemia patients categorized according to cytogenetic risk

2009 ◽  
Vol 127 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Everson Augusto Krum ◽  
Mihoko Yamamoto ◽  
Maria de Lourdes Lopes Ferrari Chauffaille
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
De Novo ◽  
Sao Paulo ◽  
São Paulo ◽  
Cross Sectional ◽  
Internal Tandem Duplication ◽  
Acute Myeloid

CONTEXT AND OBJECTIVE: The mechanism involved in leukemogenesis remains unclear and more information about the disruption of the cell proliferation, cell differentiation and apoptosis of neoplastic cells is required. DESIGN AND SETTING: Cross-sectional prevalence study at the Discipline of Hematology, Hospital São Paulo, Universidade Federal de São Paulo. METHODS: We investigated FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD+) in 40 adult patients with de novo acute myeloid leukemia (AML), categorized according to cytogenetic results, from September 2001 to May 2005. RESULTS: Thirteen patients (32.5%) were classified as presenting the favorable karyotype, 11 patients (27.5%) as an intermediate group, 7 patients (17%) as an undefined group and 9 patients (22.5%) as the unfavorable group. FLT3/ITD+ was found in 10 patients (25%): 3 with FLT3/ITD+ and favorable karyotype; 4 with FLT3/ITD+ and intermediate karyotype; 2 with FLT3/ITD+ and undefined karyotype; and only 1 with FLT3/ITD+ and unfavorable karyotype. Among the patients without FLT3/ITD+, 10 presented favorable karyotype, 8 intermediate, 4 undefined and 8 unfavorable karyotype. The cytogenetic results showed no correlations between FLT3/ITD presence and the prognostic groups (P = 0.13). We found that 2 patients were still alive more than 24 months later, FLT3/ITD+ did not influence the patients' survival rate. CONCLUSION: We found the same frequency of AML with FLT3/ITD+ in both the favorable and intermediate prognosis groups. Only one patient presented AML, FLT3/ITD+ and unfavorable karyotype (the hypothetical worst clinical situation). Therefore, the prognostic advantage of favorable cytogenetics among patients with FLT3/ITD+ remains to be elucidated, for it to be better understood.

scholarly journals Hypomethylating Agent/Venetoclax Versus Intensive Chemotherapy in Relapsed or Refractory Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2322-2322
Author(s):  
Omer Hassan Jamy ◽  
Sarah Worth ◽  
Sravanti Rangaraju ◽  
Kimo Bachiashvili ◽  
Pankit Vachhani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
High Dose ◽  
University Of Alabama ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Background: Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have limited treatment options. Outside of clinical trials and in the absence of a targetable mutation, there is no consensus on an optimal treatment regimen. Venetoclax (Ven), combined with hypomethylating agents (HMA) such as azacitadine (Aza) or decitabine (Dec), is approved as frontline treatment for elderly or unfit patients with AML. HMA/Ven is also being used frequently in the salvage setting. However, outcomes of HMA/Ven compared to IC for patients with r/r AML are largely unknown. Methods: We conducted a retrospective study to compare outcomes of adult patients (>18y) with r/r AML treated with either HMA/Ven or IC at the University of Alabama at Birmingham. Patients treated with HMA/Ven were matched in a 1:1 ratio to patients receiving IC following a hierarchal algorithm based on age, ELN risk stratification, time to relapse (primary refractory/<6m vs. ≥6m) and line of therapy. Treatment with HMA consisted of either Aza 75mg/m 2 for 7 days or Dec 20mg/m 2 for 5 days. Venetoclax was administered at an effective dose of 400mg daily for 21-28 days per cycle (dose adjusted for concomitant azole use). Results: There were 74 patients included in the analysis (HMA/Ven=37, IC=37). The baseline characteristics (Table 1) were well balanced with the exception of increased bone marrow blast percentage in the IC arm (59% vs. 39%, p=0.03). The median age of the IC and HMA/Ven groups was 56y (24-72y) and 63y (22-75y), respectively (p=0.06). Regimens in the IC arm included FLAG (n=16, 43%), FLAG-ida (n=11, 30%), CLAG-M (n=5, 14%), 7+3 (n=3, 8%), HiDAC (n=1, 2.5%) and MEC (n=1, 2.5%). In the HMA/Ven arm, 21 patients (57%) received Aza and 16 (43%) received Dec. The rate of complete remission (CR) was higher for IC (49% vs. 24%, p=0.02) whereas rate of CR with incomplete count recovery (CRi) was higher for HMA/Ven (35% vs. 8%, p=0.001) (Table 2). There was no difference in composite CR (CR+CRi) rates between the two arms (IC 57% vs. 59% HMA/Ven, p=0.8). Additionally, there was no difference in rate of refractory disease (27% vs. 27%, p=0.9) or 30-day mortality (IC 13% vs 11% HMA/Ven, p=0.6) between the two arms. More patients in the IC arm (41%), compared to the HMA/Ven (19%) arm proceeded to allogeneic stem cell transplantation (allo-sct) (p=0.04). The median overall survival (mOS) for the IC arm was 16m, compared to 8m for the HMA/Ven arm (p=0.1) (Figure 1). The mOS for patients with primary refractory/<6m relapse from remission was 10m for IC and 6m for HMA/Ven (p=0.4). The mOS for patients refractory to one cycle of intensive induction (7+3 in approximately 90% cases in both arms) was 20m for the IC arm and 5m for the HMA/Ven arm (p=0.03) (Figure 2). The mOS for patients relapsing ≥6m from remission was 15m for IC and 9m for HMA/Ven (p=0.5). There was no difference in survival based on age, ELN risk stratification or cytogenetics. Conclusion: Overall, there appears to be no significant difference in outcomes between IC and HMA/Ven for patients with r/r AML. Higher CR rates as well as ability to proceed to allo-sct are observed with IC. For patients refractory to the first cycle of intensive induction chemotherapy, a significant survival benefit was observed in those receiving IC compared to HMA/Ven. A second round of induction, preferably with a high-dose cytarabine based regimen, may provide better long term outcomes for these patients. Figure 1 Figure 1. Disclosures Vachhani: CTI BioPharma Corp: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Blueprint Medicines: Consultancy; Pfizer: Consultancy; Seattle Genetics: Research Funding; Astellas Pharma: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham: Current Employment; Jazz Pharmaceuticals: Consultancy.

scholarly journals Survival of patients diagnosed with subsets of lymphoid neoplasms and acute myeloid leukemia from 2000 to 2010 in the Vale do Paraíba, State of São Paulo: are we going the right way?

2012 ◽  
Vol 34 (2) ◽  
pp. 168-170
Author(s):  
Fernando Callera ◽  
Alvaro Azevedo Vital Brasil ◽  
Anna Raquel de Lima Casali ◽  
Carla Cecília Mulin ◽  
Evandro Secchi Rosa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Sao Paulo ◽  
São Paulo ◽  
Lymphoid Neoplasms ◽  
The Right ◽  
Acute Myeloid

scholarly journals The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings

2021 ◽  
Vol 8 ◽  
pp. 204993612110365
Author(s):  
Kundan Mishra ◽  
Suman Kumar ◽  
Sandeep Ninawe ◽  
Rajat Bahl ◽  
Ashok Meshram ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Febrile Neutropenia ◽  
Burkholderia Cepacia ◽  
Myeloid Leukemia ◽  
Tertiary Care ◽  
Care Hospital ◽  
Significant Difference ◽  
The Mean ◽  
Acute Myeloid

Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p = 0.063). Thirteen patients (23.63%) died during the study period. Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. Conclusion: Infections continues to be a major cause of morbidity and mortality among AML patients.

scholarly journals Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rongqun Guo ◽  
Mengdie Lü ◽  
Fujiao Cao ◽  
Guanghua Wu ◽  
Fengcai Gao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Cell ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Significant Difference ◽  
Cell Phenotypes ◽  
Acute Myeloid

Abstract Background Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components. Methods Using a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the immune cell phenotypes, function, and developmental trajectory of bone marrow (BM) samples from 16 AML patients and 4 healthy donors, but not AML blasts. Results We observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AML patients. We also identified several unique immune cell types including T helper cell 17 (TH17)-like intermediate population, cytotoxic CD4+ T subset, T cell: erythrocyte complexes, activated regulatory T cells (Treg), and CD8+ memory-like subset. Emerging AML cells remodels the BM immune microenvironment powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional immune effectors, expending immune-activated types, and promoting the formation of suppressive subsets. Conclusion Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.

Genomics of Acute Myeloid Leukemia Diagnosis and Pathways

2017 ◽  
Vol 35 (9) ◽  
pp. 934-946 ◽  
Author(s):  
Lars Bullinger ◽  
Konstanze Döhner ◽  
Hartmut Döhner
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Clinical Care ◽  
Clonal Expansion ◽  
Disease Classification ◽  
Disease Evolution ◽  
Myeloid Neoplasms ◽  
Increased Risk ◽  
Acute Myeloid

In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such mutations may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. In contrast, mutations involving NPM1 or signaling molecules (eg, FLT3, RAS) typically are secondary events that occur later during leukemogenesis. Genetic data are now being used to inform disease classification, risk stratification, and clinical care of patients. Two new provisional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been included in the current update of the WHO classification of myeloid neoplasms and AML, and mutations in three genes— RUNX1, ASXL1, and TP53—have been added in the risk stratification of the 2017 European LeukemiaNet recommendations for AML. Integrated evaluation of baseline genetics and assessment of minimal residual disease are expected to further improve risk stratification and selection of postremission therapy. Finally, the identification of disease alleles will guide the development and use of novel molecularly targeted therapies.

Analysis of Efficacy and Prognostic Factors of CLAG Treatment in Chinese Patients with Refractory or Relapsed Acute Myeloid Leukemia

2018 ◽  
Vol 141 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Li Wang ◽  
Jun Xu ◽  
Xiaolong Tian ◽  
Tingting Lv ◽  
Guolin Yuan
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Risk Stratification ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Remission Rate ◽  
Chinese Patients ◽  
Acute Myeloid

Background/Aims: The aim of this work was to investigate the efficacy and predictive factors of CLAG treatment in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients. Methods: Sixty-seven R/R AML patients were enrolled in this prospective cohort study and treated by a CLAG regimen: 5 mg/m2/day cladribine (days 1–5), 2 g/m2/day cytarabine (days 1–5), and 300 μg/day filgrastim (days 0–5). The median follow-up duration was 10 months. Results: A total of 57 out of 67 patients were evaluable for remission after CLAG therapy, of whom 57.9% achieved a complete remission (CR) and the overall remission rate was 77.2%. The median overall survival (OS) was 10.0 months, with a 1-year OS of 40.3 ± 6.0% and 3-year OS of 16.7 ± 5.7%. CR at first induction after the initial diagnosis was associated with a favorable CR. Age above 60 years, high risk stratification, second or higher salvage therapy, and bone marrow (BM) blasts ≥42.1% were correlated with an unfavorable CR. Secondary disease, age ≥60 years, high risk stratification, and second or higher salvage therapy were associated with worse OS. Patients developed thrombocytopenia (41, 61%), febrile neutropenia (37, 55%), leukopenia (33, 49%), neutropenia (18, 27%), and anemia (9, 13%). Conclusion: CLAG was effective and well tolerated for R/R AML. BM blasts ≥42.1%, age ≥60 years, high risk stratification, and second or higher salvage therapy were independent factors for a poor prognosis.

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