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.

scholarly journals Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 339-347 ◽  
Author(s):  
Arati V. Rao
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Patient Population ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
The Elderly ◽  
Future Research ◽  
Strongly Correlated ◽  
Patient Will ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a disease of the elderly, but less than half of these patients are offered therapy despite the evidence of better survival with treatment in this patient population. Assessing fit, vulnerable, and frail older adults with AML remains a challenge for the treating oncologist. A majority of AML patients are elderly and often have significant comorbidities, lack of social support, and older caregivers. Performance status (PS), a subjective measure of how a patient will tolerate cancer chemotherapy, has been strongly correlated with mortality in older AML patients. However, a large portion of older adults have poor PS as a result of their underlying AML, and these patients may end up being undertreated. Conversely, some patients with excellent PS unexpectedly end up with excessive toxicity and mortality. The treating physician thus needs a more objective and comprehensive method to differentiate patients along the fit-frail spectrum irrespective of their chronological age. For more than a decade, comprehensive geriatric assessment has been shown to improve routine oncology assessment by adding information about the functional, emotional, cognitive, and social status of older patients with cancer. In addition to the chronological and functional age, there is an attempt to quantify a patient’s biological age to aid in better decision making. This chapter attempts to review the clinical challenges of AML treatment in the elderly population and to highlight the current literature and future research required to be able to assess fitness and maximize therapeutic options in this heterogeneous patient population.

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.

Acute Myeloid Leukemia (AML). Diagnosis, Therapy and Outcome Results from Tawam Hospital. a Retrospective Review

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5254-5254
Author(s):  
Arif Alam ◽  
Ali Tahir ◽  
Masood H Syed ◽  
Sabir Hussain ◽  
Amar Lal ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Supportive Care ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
High Dose ◽  
Lost To Follow Up ◽  
Acute Myeloid

Abstract Introduction Acute Myeloid leukemia (AML) is a heterogeneous group of malignant disorders of myeloid hematopoetic cells. These cells have a maturation arrest in different stages of development leading to accumulation of immature cells. This gives rise to the different symptoms and signs of disease secondary to anemia, thrombocytopenia and neutropenia. The current WHO classification broadly divides AML into 4 main groups based on morphology, immunophenotyping, genetics and clinical features. These include AML with recurrent genetic abnormalities, AML with myelodysplasia related changes; therapy related AML and AML not otherwise specified (NOS). Therapeutically AML can be divided into 2 main groups; Acute promyelocytic leukemia (APML) and non APML. Methods Tawam Tumor registry was searched for patients with diagnosis of AML from January 2010 till December 2012. Patient records were then reviewed and data was collected. Results We identified 49 patients with pathologically confirmed diagnosis of AML. 19/49 patients were diagnosed with AML with recurrent cytogenetic, 5/49 with MDS related or therapy related and 25 with AML NOS Cytogenetic Analysis of this cohort of 49 patients with AML showed that 15 patients (30%) had APML with 15;17 translocation, 4 patients had 8;21 translocation, 5 had complex or poor risk cytogenetic while 13 had normal karyotype. In 12/49 patients Karyotyping failed due to growth failure. Status of FLT3 and NPM1 are not known for the entire cohort. Demographics The median age of the cohort was 38 years (range 20 to 84 years). Older adults (age 65 years or more) make a minority of this cohort (8%). Male to female ration was 3.5:1. Treatment In patients with Non APML Induction therapy was a combination of Cytarabine and Idarubicin for adults < 65 years of age and with good performance status. Older adults or adults with poor performance status or co-morbidities were either given hypomehtylating agents, Clofarabine or supportive care. Patients achieving complete remission (CR) were given consolidation with High Dose Cytarabine (HIDAC) as per CALGB protocol. Only a minority of patients were able to go for allogeneic stem cell transplantation in CR1 Patients with APML were treated with ATRA, Idarubicin/Mitoxantrone and Cytarabine as per PETHEMA protocol on a risk adjusted plan. This was followed by 2 year maintenance with ATRA, 6 MP and Methotrexate. Outcome of Treatment In non APML patients 62 % (17) achieved CR with induction therapy. Induction therapy failure was observed in 18 % (5) while there were 5 early deaths observed (during aplasia). 7 patients were treated with hypomethylating agents or best supportive care. Only 1patient was able to achieve CR (after cycle 4 of 5-azacitidine). Consolidation therapy was given to 17 patients achieving CR. With a median follow up of 15 months (range 9-24 months) 9 patients are alive and disease free while 17 patients have been lost to follow up. 8 out of these 17 patients were in remission at their last follow up. In APML patients the CR rate was 93%. There were no cases of induction failure and only 1 case of early death (7%) due to hemorrhage. With a median follow up of 17 months (range 11-41 months) 11 patients are in molecular CR while 3 have been lost to follow up. Conclusion This is the first analysis of patients who were diagnosed with AML in a tertiary care center in UAE. The results show that the median age of patients our cohort is low as compared to international reports (approximately 38 vs. 65 years). Older adults (> 65 years of age) make only a minority of the AML cohort in Tawam Hospital. Response to induction therapy is comparable to international standards (60-80%) for AML and > 90% for APML. We also report a twofold higher incidence of APML as compared to internationally reported data (30% vs.12%). This has a very significant diagnostic and therapeutic impact on the management of AML patients at our institute leading to increase vigilance and institution of ATRA at the earliest clinical suspicion of APML. Disclosures Alam: BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Hussain:BMS: Honoraria; Novartis: Honoraria. Lal:BMS: Honoraria; novartis: Honoraria.

scholarly journals Treating acute myeloid leukemia in older adults

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Eunice S. Wang
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Decision Making ◽  
Performance Status ◽  
Treatment Algorithm ◽  
Epidemiological Data ◽  
Long Term Treatment ◽  
Definitive Therapy ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a disease of older adults, with a median age of 67 years at presentation. In the past, only a third of older patients (defined as individuals older than 60-65 years of age) with AML received definitive therapy for their disease due to concerns about their overall fitness and potential treatment-related mortality. However, compelling epidemiological data have shown unequivocally that older AML patients up to 80 years old both tolerate and survive longer after therapy than their untreated counterparts. Current therapeutic options for elderly individuals with AML include intensive chemotherapy with a cytarabine and anthracycline backbone, hypomethylating agents (decitabine and azacitidine), low-dose cytarabine, investigational agents, and supportive care with hydroxyurea and transfusions. Over the last few years, there has been increasing debate regarding the appropriate therapeutic approach to take in older adults given the diversity of the geriatric patient population and heterogeneous AML disease biology. This article discusses how performance status, comorbidities, disease characteristics, quality of life concerns, and long-term treatment goals affect the selection of appropriate therapy for older adults with AML. Risks and benefits of each treatment approach based on the most recent medical literature are discussed. Finally, a treatment algorithm summarizing these data and incorporating geriatric assessment and molecular and cytogenetic markers predictive of therapeutic response is proposed to aid in the clinical decision-making process.

Performance status and comorbidities on outcome of hypomethylating therapy in older adults (≥60 years old) with acute myeloid leukemia.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 7058-7058
Author(s):  
Anju Chana ◽  
Laurie Ann Ford ◽  
Elizabeth A. Griffiths ◽  
James E. Thompson ◽  
Meir Wetzler ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Acute Myeloid

Multi-Site 11-Year Experience of Less-Intensive versus Intensive Therapies in Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Author(s):  
Mohamed Lotfy Sorror ◽  
Barry E Storer ◽  
Amir T. Fathi ◽  
Andrew M. Brunner ◽  
Aaron T Gerds ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prospective Cohort ◽  
Myeloid Leukemia ◽  
Retrospective Cohort ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Mortality Risks ◽  
Comorbidity Burden ◽  
Acute Myeloid

Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia, assuming they are better than intensive induction. Using an AML-composite model (AML-CM) that assigns higher scores to older age, increased comorbidity-burdens and adverse cytogenetic-risks, we defined three distinct prognostic groups, and within each, compared outcomes after less-intensive versus intensive induction therapies in a multicenter retrospective cohort (n=1292) treated at six institutions from 2008-2012 and a prospective cohort (n=695) treated at thirteen institutions from 2013-2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physicians' perceptions of cure. In the retrospective cohort, recipients of less-intensive therapies were older, had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks for mortality in AML-CM scores of 4-6, 7-9, and ≥10. Results were independent from receipt of allogeneic transplants and similar in those aged 70-79 years old. In the Prospective cohort, the two groups were similar in baseline QOL, geriatric assessment, and patients' outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS and chances of cure, mortality risks and QOL were similar. Less-intensive recipients had lessened length of hospitalization (LOH). Our studies question the survival or QOL, except LOH, benefits from less-intensive therapies in patients with AML, including those aged 70-79 years or with high comorbidity-burden. A randomized trial in older/medically infirm patients is needed to better assess the value of less-intensive, intensive, or a combination of both therapies. ClinicalTrials.gov #NCT01929408.

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.

New Strategies for the Treatment of Acute Myeloid Leukemia Including Antibodies and Other Novel Agents

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Martin S. Tallman
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Cytotoxic Agents ◽  
High Dose ◽  
Farnesyltransferase Inhibitors ◽  
Younger Adults ◽  
The Impact ◽  
Acute Myeloid

Abstract The prognosis for younger adults (≤ 55–60 years) with acute myeloid leukemia (AML) has improved during the last four decades. However, there has been little progress in the treatment of older adults. This disappointing observation is important because the median age of patients with AML is about 70 years. Approximately 60%–80% of younger adults with AML achieve complete remission (CR) with the cytotoxic agents cytarabine and an anthracycline such as daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only 30%–40% of such patients are alive and disease-free at 5 years. Among older adults, CR is achieved in 40%–55%, but there are very few long-term survivors. Many studies have evaluated the impact of alternative doses and schedules, as well as additional cytotoxic drugs, on the prognosis for this group of patients. The outcome has not improved substantially beyond that achieved with conventional doses of an anthracycline and cytarabine followed by high-dose cytarabine consolidation. Several factors identified at diagnosis can predict outcome. The most important of these is the karyotype of the leukemic cells. Another critical factor is the presence of transmembrane transporter proteins, which confer multidrug resistance and mutations in or overexpression of specific genes such as WT1, C/EBPα, BAX, and BCL-2/BAX ratio, BAALC, EVI1, KIT and FLT3. The development of specific agents directed at gene mutations, signal transduction pathways and unique cell surface antigens provide the foundation for new therapeutic strategies. Such agents include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance inhibitors, farnesyltransferase inhibitors, histone deacetylase and proteosome inhibitors, antiangiogenesis agents, FLT3 inhibitors, apoptosis inhibitors, and nucleoside analogs. All of these agents can potentially address the heterogeneous abnormalities in AML and significantly improve the outcome for patients.

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