scholarly journals AML Risk Stratification Models Utilizing ELN-2017 Guidelines and Additional Prognostic Factors:  A SWOG Report

2020 ◽  
Author(s):  
Era L Pogosova-Agadjanyan ◽  
Anna Moseley ◽  
Megan Othus ◽  
Frederick R. Appelbaum ◽  
Thomas R. Chauncey ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Validation Cohort ◽  
Performance Status ◽  
Independent Set ◽  
Prognostic Models ◽  
Acute Myeloid

Abstract Background The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice.Methods In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, N = 185) who received intensive chemotherapy. Models were validated in an independent set of similarly treated patients (validation cohort, N = 166).Results Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age < 55). Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models, which excluded results for ASXL1, CEBPA, RUNX1 and TP53, demonstrated a limited overall contribution to risk stratification across the entire population, given the low frequency of mutations and confounding risk factors.Conclusions While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification.

scholarly journals Geriatric perspective: how to assess fitness for chemotherapy in acute myeloid leukemia

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Heidi D. Klepin
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Functional Decline ◽  
Improve Risk Stratification ◽  
Therapeutic Decisions ◽  
Comorbidity Burden ◽  
Acute Myeloid

Abstract Characterizing “fitness” in the context of therapeutic decisions for older adults with acute myeloid leukemia (AML) is challenging. Available evidence is strongest in identifying those older adults who are frail at the time of diagnosis by characterizing performance status and comorbidity burden. However, many older adults with adequate performance status and absence of major comorbidity are “vulnerable” and may experience clinical and functional decline when stressed with intensive therapies. More refined assessments are needed to differentiate between fit and vulnerable older adults regardless of chronologic age. Geriatric assessment has been shown to add information to routine oncology assessment and improve risk stratification for older adults with AML. This review highlights available evidence for assessment of “fitness” among older adults diagnosed with AML and discusses future treatment and research implications.

Comparison of Outcome and Prognosis of 248 Elderly Patients with Acute Myeloid Leukemia Treated with Standard-Dose or Low-Intensity Induction Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2540-2540
Author(s):  
Jianda Hu ◽  
Yi Chen ◽  
Xiaoyun Zheng ◽  
Zhihong Zheng ◽  
Ting Yang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Performance Status ◽  
Low Intensity ◽  
Induction Cycle ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a disease of older adults, with a median onset age at about 65-70 years. The treatment outcome of AML appears to be poorer with the age increasing, in part due to the poor performance status, concomitant end-organ dysfunction, higher incidence of unfavorable cytogenetic findings, frequent involvement of a more immature leukemic precursor clone, multidrug resistance mediated by MDR1/P-glycoprotein, and the presence of antecedent hematopoietic disorders. Treatment of elderly patients with AML remains highly challenging and controversial. The overall survival rates at 5-year of ≥ 60 years old AML patients are still less than 20% by now. At present, standard-dose induction chemotherapy using a cytarabine plus idarubicin(IA regimen) or daunorubicin (DA regimen) was considered by most to be the most effective upfront AML induction therapy. However, there are still quite a number of elderly patients could not tolerate because of poor performance status and complications. Therefore, low-intensity chemotherapy, including CAG regimen, which combine low-dose cytarabine, aclacinomycin and granulocyte colony-stimulating factor(G-CSF), was used for those were not appropriate for receiving standard-dose chemotherapy. Here we retrospectively analyzed the outcome and prognosis of elderly patients with AML treated with standard-dose or low-intensity induction therapy. 248 elderly patients with acute myeloid leukemia(AML) who received standard-dose or low-intensity induction therapy were enrolled in this retrospective clinical study, 186 patients in standard-dose group with 144 in IA and 42 in DA, 62 cases in low-intensityCAG group. The maininclusion criteria included age ≥ 60 years old, ECOG performance status ≤ 2, without severe complication of heart, liver, kidney or other important organ. The patients received standard-dose or low-intensity induction regimen according to their performance status and patient preference. 144 patients received IA regimen(idarubicin 10mg/m2/d ,d1-3; cytarabine 100mg/m2, q12h, d1-5 or 7), 42 patients received DA regimen(daunorubicin 60mg/m2/d, d1-3; cytarabine 100mg/m2 q12h, d1-5 or 7), and 62 patients received CAG regimen (cytarabine 10mg/m2 q12h, d1-14; aclacinomycin 20mg qd, d1-4; G-CSF 200ug/m2 qd, d0-14, or until bone marrow recover). The median survival time was 9.2 months. 1-year , 3-year and 5-year overall survival(OS) were 42.2%, 18.9% and 13.5%, respectively. After first induction cycle, complete remission(CR) rate was 49.3% in IA group, 35.7% in DA group and 32.3% in CAG group (P = 0.046). The median OS for IA, DA and CAG group were 10.0 months, 9.7months and 7.5 months, respectively. The early mortality of induction therapy and recurrence rate of three regimens showed no difference. IA could improve the long term survival compared to CAG and DA, with 3-year OS: 23.5%,15.9% and 8.3%, respectively; 5-year OS: 19.4%, 6.3%, and 0, respectively (P<0.01). The 67.0% patients relapsed within 24 months, with median relapse time of 8.4 months, 14.6 months and 8.3 months for IA, DA and CAG regimen, respectively. Moreover, Kaplan-Meier analysis showed that 7 parameters were adverse prognostic factors for OS, including age ≥ 70 years old, poor ECOG performance status, unfavorable cytogenetics, non-remission after first induction cycle, white blood cell (WBC) counts ≥ 50×10^9/L, percentage of bone marrow (BM) blast ≥ 80% and higher lactic dehydrogenase (LDH) . Multivariable analysis identified non-remission after first induction cycle (HR = 6.141, 95%CI: 3.585-10.52, P = 0.000) and LDH ≥ 490 IU/L(HR = 1.001, 95%CI: 1.000-1.001, P = 0.000) as independent significantly prognostic factors for OS. In conclusion, Our present data showed that standard-dose IA regimen could improve CR rate and prolong the survival time compared to low-intensity CAG regimen, and CAG regimen still has a certain therapeutic effect for those unfit for intensive chemotherapy. Recurrence is still a serious problem for those who do not receive Allo-HSCT for consolidation after CR. All prognostic factors should be considered before induction therapy to make sure the patients receive the best individualized treatment. Disclosures No relevant conflicts of interest to declare.

Sarcopenia and Adipopenia Are Independent Prognostic Factors in Patients with Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4953-4953
Author(s):  
Nobuhiko Nakamura ◽  
Yuhei Shibata ◽  
Takuro Matsumoto ◽  
Hiroshi Nakamura ◽  
Junichi Kitagawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adipose Tissue ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Ct Images ◽  
The Impact ◽  
Acute Myeloid

Abstract Background: The response to treatment and overall survival of patients with acute myeloid leukemia (AML) are heterogeneous. A number of prognostic factors related to patient and tumor characteristics have been described for AML, including age, performance status, and karyotype. The depletion of skeletal muscle (sarcopenia) and adipose tissue (adipopenia) are known to be associated with unfavorable prognosis in patients with some malignant diseases including lymphoma. Here, we studied the impact of sarcopenia and adipopenia on clinical outcomes of adult AML. Patients and Methods: We retrospectively analyzed 70 patients with adult AML (age ≥ 18 years) who received chemotherapy at Gifu University Hospital between December 2004 and September 2014. Skeletal muscle and adipose tissue were measured by the analysis of CT images at the L3 level before treatment. CT images were analyzed using SliceOMatic version 4.3 software (TomoVision, Montreal, QB, Canada), which enables specific tissue demarcation using previously reported Hounsfield unit (HU) thresholds. The CT HU thresholds were -29 to 150 for skeletal muscles and -190 to -30 and -50 to -150 for subcutaneous and visceral adipose tissue, respectively. These values were normalized for stature in order to calculate skeletal muscle index (SMI, cm2/m2) and adipose tissue index (ATI, cm2/m2). Results: Median age at diagnosis was 57 years (18-84 years), with 37 males and 33 females. SMI was significantly higher in male than female patients (P &lt; 0.001). ATI was significantly higher in patients aged 60 years and over than in those under 60 years (P &lt; 0.05). The sex-specific cut-offs for the SMI and ATI were determined by ROC curve analysis. Thirty-five (50%) and 31 (44%) patients were defined as sarcopenia and adipopenia, respectively. Sarcopenia and adipopenia did not significantly differ among various FAB subtypes or cytogenetic risk profiles. The rate of patients with poor performance status (ECOG ≥ 2) was significantly higher in the sarcopenic group (80% vs 45%, P &lt; 0.05), whereas not in the adipopenic group (40% vs 47%). With a median follow-up of 33.5 months, the 3-year overall survival (OS) in the sarcopeniac group was 34% compared with 74% in the non-sarcopenic group (P &lt; 0.001, Figure 1A) and 32% in the adipopenic group compared with 72% in the non-adipopenic group (P &lt; 0.005, Figure 1B). In a multivariate analysis, sarcopenia (HR = 2.84, CI = 1.08-8.08, P &lt; 0.05) and adipopenia (HR = 2.85, CI = 1.19-7.24, P &lt; 0.05) remained predictive of OS. Conclusion: Sarcopenia and adipopenia are independent prognostic factors in patients with AML. Evaluation of skeletal muscle and adipose tissue depletion by CT imaging is a useful objective tool to predict patient outcomes, but a larger prospective study is needed to confirm this effect. Figure 1. Overall survival according to sarcopenic (A) and adipopenic (B) status. Figure 1. Overall survival according to sarcopenic (A) and adipopenic (B) status. Disclosures No relevant conflicts of interest to declare.

New Prognostic Markers in Acute Myeloid Leukemia: Perspective from the Clinic

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 47-55 ◽  
Author(s):  
James M. Foran
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Prognostic Markers ◽  
Performance Status ◽  
Response To Therapy ◽  
Proteomic Profiling ◽  
New Targets ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a disease with marked heterogeneity in both response to therapy and survival. Cytogenetics, age, and performance status have long determined prognosis and therapy. The advent of molecular diagnostics has heralded an explosion in new prognostic factors, including gene mutations in KIT, FLT3 (Fms-like tyrosine kinase 3), NPM1 (nucleophosmin 1), and CEBPA (CCAAT enhancer-binding protein-α). Microarray technology can now identify unique gene expression signatures associated with prognosis. Similarly microRNA expression, single nucleotide polymorphism arrays, and DNA methylation signatures have recently described important new prognostic subgroups of AML, and are contributing to our understanding of AML disease biology. Combined with proteomic profiling, these technologies have helped identify new targets and signaling pathways, and may soon help to identify individual patients likely to benefit from specific therapies, including allogeneic hematopoietic cell transplantation. In summary, new clinical and molecular prognostic markers have begun to significantly improve our understanding of AML biology. We are now close to a time when we will be able to use these prognostic factors and technologies to identify new targets for therapy and to determine who may benefit from that therapy, and ultimately change how we treat individual patients with AML.

Results of Intensive Chemotherapy in 998 Patients Aged 65 Years or Older with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome - Predictive Prognostic Models for Outcome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1846-1846
Author(s):  
Elias Jabbour ◽  
Hagop Kantarjian ◽  
Susan O’Brien ◽  
Jorge Cortes ◽  
Francis Giles ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Multivariate Analyses ◽  
Survival Rates ◽  
Mortality Rates ◽  
Prognostic Models ◽  
Intensive Chemotherapy ◽  
Elderly Aml ◽  
Acute Myeloid

Background. Elderly patients (age ≥ 65 years) with acute myeloid leukemia (AML) have a poor prognosis. AML-type therapy results are often derived from studies in younger patients and may not apply to elderly AML. Many investigators and oncologists advocate, at times, only supportive care or frontline single agents, phase I–II studies, low intensity regimens, or “targeted” therapies. Baseline expectations for outcomes of elderly AML with “standard” AML-type therapy are not well defined. Study Aims. To develop prognostic models for complete response (CR), induction (8-week) mortality, and survival rates in elderly AML, which define expectations with standard AML type therapy. Patients and Methods. 998 patients age ≥ 65 years with AML or high-risk myelodysplastic syndrome (≥ 10% blasts) treated with intensive chemotherapy between 1980 and 2004 were analyzed. Univariate and multivariate analyses of prognostic factors used standard methods. Results. The overall CR rate was 45% and induction mortality 29%. Multivariate analyses identified consistent independent poor prognostic factors for CR, 8-week mortality, and survival. These included age ≥ 75 years, unfavorable karyotypes (often complex), poor performance (3–4 ECOG), longer duration of antecedent hematologic disorder, treatment outside the laminar airflow room, and abnormal organ functions. Patients could be divided into: 1) a favorable group (about 20% of patients) with expected CR rates above 60%, induction mortality rates below 10%, and 1-year survival rates above 50%; 2) an intermediate group (about 50% of patients) with expected CR rates of 50%, induction mortality rates of 30%, and 1-year survival rates of 30%; and 3) an unfavorable risk group (about 25% to 30% of patients) with expected CR rates of less than 20%, induction mortality rates above 50%, and 1-year survival rates of less than 10%. Conclusions. Prognostic models were developed for elderly patients with AML, which may assist in therapeutic and investigational decisions.

scholarly journals Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a Multi-Gene Panel and Nomogram Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Li-Xin Wu ◽  
Hao Jiang ◽  
Ying-Jun Chang ◽  
Ya-Lan Zhou ◽  
Jing Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Validation Cohort ◽  
Low Risk ◽  
Training Cohort ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myeloid

BackgroundApproximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.MethodsIn this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method.ResultsAt least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P &lt;0.001 in training cohort; 87.5% vs. 18.2%, P =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% vs. 32.6%, P &lt;0.001), survival (96.9% vs. 63.6%, P =0.001) and CIR (7.2% vs. 65.8%, P &lt;0.001) in high-risk patients but not low-risk patients (LFS, 77.4% vs. 88.9%, P =0.424; survival, 83.9% vs. 95.5%, P =0.173; CIR, 11.7% vs. 11.1%, P =0.901).ConclusionsOur study indicated that biCEBPA mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in biCEBPA mutant-positive CN-AML patients.

scholarly journals Sarcopenia and adipopenia are independent prognostic factors in patients with acute myeloid leukemia

2015 ◽  
Vol 26 ◽  
pp. vii84
Author(s):  
Nobuhiko Nakamura ◽  
Takuro Matsumoto ◽  
Yuhei Shibata ◽  
Junichi Kitagawa ◽  
Nobuhiro Kanemura ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Acute Myeloid

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.

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