Special Issue "Treatment of Older Adults with Acute Myeloid Leukemia"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2018)

Special Issue Editor

Guest Editor
Dr. Roland B. Walter

Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
Associate Professor of Medicine, Department of Medicine/Division of Hematology, University of Washington School of Medicine
Adjunct Associate Professor, Department of Epidemiology, University of Washington School of Public Health, 1100 Fairview Ave N, D2-190 Seattle, WA 98109-1024, USA
Website | E-Mail
Phone: +1-206-667-3599
Fax: +1-206-667-6519
Interests: acute myeloid leukemia; antibody-based immunotherapy; CD33; clinical trials; measurable (“minimal”) residual disease; predictive modeling

Special Issue Information

Dear Colleagues,

Curative-intent treatment algorithms with multi-agent chemotherapy and, often, hematopoietic cell transplantation are well-established for children, adolescents, and younger adults with acute myeloid leukemia (AML). However, with a median age of close to 70 years at diagnosis, AML primarily affects older adults. In these individuals, it is much less clear which treatment strategy optimizes the quantity and/or quality of life. Particular challenges the clinician faces in this patient population include increased therapeutic resistance and reduced tolerance to intensive therapies, especially when co-morbidities are present. The presumption that risks are not commensurate with potential benefits may explain why a large portion of older adults with AML never receives disease-directed therapy—despite data indicating that outcomes are improved if essentially all of these patients are given AML therapy. This Special Issue will focus on various aspects of the care of older adults with AML, including the decision-making process regarding most appropriate therapy (e.g., assessment of the fitness for AML therapy, determination of treatment intensity, and choice of “investigational” versus “standard” treatment), available and emerging intensive and non-intensive chemotherapy and transplant options, approaches to monitor treatment effects over time, quality of life considerations, and supportive care demands.

 

Dr. Roland B. Walter
Guest Editor

Manuscript Submission Information

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Keywords

  • acute myeloid leukemia
  • chemotherapy
  • geriatric assessment
  • hematopoietic cell transplantation
  • investigational therapy
  • measurable (“minimal”) residual disease
  • quality of life
  • supportive care
  • treatment intensity

Published Papers (9 papers)

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Review

Open AccessReview Current Therapeutic Results and Treatment Options for Older Patients with Relapsed Acute Myeloid Leukemia
Cancers 2019, 11(2), 224; https://doi.org/10.3390/cancers11020224
Received: 22 January 2019 / Revised: 5 February 2019 / Accepted: 10 February 2019 / Published: 14 February 2019
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Abstract
Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit [...] Read more.
Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate–high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients’ characteristics or physicians’ attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as “promising” in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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Open AccessReview Autologous Transplantation for Older Adults with AML
Cancers 2018, 10(9), 340; https://doi.org/10.3390/cancers10090340
Received: 13 July 2018 / Revised: 17 September 2018 / Accepted: 17 September 2018 / Published: 19 September 2018
Cited by 2 | PDF Full-text (838 KB) | HTML Full-text | XML Full-text
Abstract
While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are [...] Read more.
While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients. However, prospective studies in older AML patients assessing the benefit of autologous HCT compared to chemotherapy consolidation or allogeneic transplantation are lacking. Consequently, clinicians face the dilemma that there is considerable ambiguity on the most appropriate consolidation treatment for older AML patients in CR1. This review highlights the possible role of autologous HCT for consolidation in older AML patients reaching CR1 after induction treatment. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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Open AccessReview Bridging Strategies to Allogeneic Transplant for Older AML Patients
Cancers 2018, 10(7), 232; https://doi.org/10.3390/cancers10070232
Received: 7 May 2018 / Revised: 27 June 2018 / Accepted: 6 July 2018 / Published: 11 July 2018
Cited by 2 | PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
Treatment options for older patients with intermediate or high-risk acute myeloid leukemia (AML) remain unsatisfactory. Allogeneic stem cell transplantation, the treatment of choice for the majority of younger AML patients, has been hampered in elderly patients by higher treatment related mortality, comorbidities and [...] Read more.
Treatment options for older patients with intermediate or high-risk acute myeloid leukemia (AML) remain unsatisfactory. Allogeneic stem cell transplantation, the treatment of choice for the majority of younger AML patients, has been hampered in elderly patients by higher treatment related mortality, comorbidities and lack of a suitable donor. With the higher availability of suitable donors as well as of reduced intensity conditioning regimens, novel low intensity treatments prior to transplantation and optimized supportive care, the number of older AML patients being successfully transplanted is steadily increasing. Against this background, we review current treatment strategies for older AML patients planned for allogeneic stem cell transplantation based on clinical trial data, discussing differences between approaches with advantages and pitfalls of each. We summarize pre-treatment considerations that need to be taken into account in this highly heterogeneous older population. Finally, we offer an outlook on areas of ongoing clinical research, including novel immunotherapeutic approaches that may improve access to curative therapies for a larger number of older AML patients. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
Open AccessFeature PaperReview Geriatric Assessment in Older Patients with Acute Myeloid Leukemia
Cancers 2018, 10(7), 225; https://doi.org/10.3390/cancers10070225
Received: 14 June 2018 / Revised: 3 July 2018 / Accepted: 5 July 2018 / Published: 6 July 2018
Cited by 1 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health [...] Read more.
The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
Open AccessFeature PaperReview Role of Minimal (Measurable) Residual Disease Assessment in Older Patients with Acute Myeloid Leukemia
Cancers 2018, 10(7), 215; https://doi.org/10.3390/cancers10070215
Received: 2 May 2018 / Revised: 18 June 2018 / Accepted: 18 June 2018 / Published: 26 June 2018
Cited by 2 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text
Abstract
Minimal (or measurable) residual (MRD) disease provides a biomarker of response quality for which there is robust validation in the context of modern intensive treatment for younger patients with Acute Myeloid Leukemia (AML). Nevertheless, it remains a relatively unexplored area in older patients [...] Read more.
Minimal (or measurable) residual (MRD) disease provides a biomarker of response quality for which there is robust validation in the context of modern intensive treatment for younger patients with Acute Myeloid Leukemia (AML). Nevertheless, it remains a relatively unexplored area in older patients with AML. The lack of progress in this field can be attributed to two main reasons. First, physicians have a general reluctance to submitting older adults to intensive chemotherapy due to their frailty and to the unfavourable biological disease profile predicting a poor outcome following conventional chemotherapy. Second, with the increasing use of low-intensity therapies (i.e., hypomethylating agents) differing from conventional drugs in mechanism of action and dynamics of response, there has been concomitant skepticism that these schedules can produce deep hematological responses. Furthermore, age dependent differences in disease biology also contribute to uncertainty on the prognostic/predictive impact in older adults of certain genetic abnormalities including those validated for MRD monitoring in younger patients. This review examines the evidence for the role of MRD as a prognosticator in older AML, together with the possible pitfalls of MRD evaluation in older age. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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Open AccessReview Immunosenescence and Immunotherapy in Elderly Acute Myeloid Leukemia Patients: Time for a Biology-Driven Approach
Cancers 2018, 10(7), 211; https://doi.org/10.3390/cancers10070211
Received: 14 May 2018 / Revised: 9 June 2018 / Accepted: 19 June 2018 / Published: 22 June 2018
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Abstract
Acute myeloid leukemia (AML) is a disease, which mainly affects the elderly population. Unfortunately, the prognosis of patients aged >65 years is dismal, with 1-year overall survival approaching 10% with conventional therapies. The hypothesis of harnessing the immune system against cancer, including leukemia, [...] Read more.
Acute myeloid leukemia (AML) is a disease, which mainly affects the elderly population. Unfortunately, the prognosis of patients aged >65 years is dismal, with 1-year overall survival approaching 10% with conventional therapies. The hypothesis of harnessing the immune system against cancer, including leukemia, has been postulated for a long time, and several clinical attempts have been made in this field. In the last years, we increased our knowledge about the interplay between AML and immune cells, but no major improvement has been translated, up to now, from bench to bedside. However, the outstanding results coming from the modern immuno-oncology trials with new drugs have granted a new interest for immunotherapy in AML. Accordingly, the elderly population represents an ideal target, given the low percentage of patients eligible for allogeneic stem cell transplant. With that in mind, in the era of immunotherapy, we consider immunosenescence as the optimal background to start investigating a biology-driven approach to AML therapy in the elderly. By taking into account the physiological age-related changes of immune response, more personalized and tailored use of the new drugs and strategies harnessing the immune system against AML, has the potential to increase their efficacy and impact on clinical outcomes. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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Open AccessReview Evolving Treatment Strategies for Elderly Leukemia Patients with IDH Mutations
Cancers 2018, 10(6), 187; https://doi.org/10.3390/cancers10060187
Received: 21 April 2018 / Revised: 23 May 2018 / Accepted: 4 June 2018 / Published: 6 June 2018
Cited by 4 | PDF Full-text (640 KB) | HTML Full-text | XML Full-text
Abstract
Acute myeloid leukemia (AML) is a debilitating and life-threatening condition, especially for elderly patients who account for over 50% of diagnoses. For over four decades, standard induction therapy with intensive cytotoxic chemotherapy for AML had remained unchanged. However, for most patients, standard therapy [...] Read more.
Acute myeloid leukemia (AML) is a debilitating and life-threatening condition, especially for elderly patients who account for over 50% of diagnoses. For over four decades, standard induction therapy with intensive cytotoxic chemotherapy for AML had remained unchanged. However, for most patients, standard therapy continues to have its shortcomings, especially for elderly patients who may not be able to tolerate the complications from intensive cytotoxic chemotherapy. New research into the development of targeted and alternative therapies has led to a new era in AML therapy. For the nearly 20% of diagnoses harboring a mutation in isocitrate dehydrogenase 1 or 2 (IDH1/2), potential treatment options have undergone a paradigm shift away from intensive cytotoxic chemotherapy and towards targeted therapy alone or in combination with lower intensity chemotherapy. The first FDA approved IDH2 inhibitor was enasidenib in 2017. In addition, IDH1 inhibitors are in ongoing clinical studies, and the oral BCL-2 inhibitor venetoclax shows preliminary efficacy in this subset of patients. These new tools aim to improve outcomes and change the treatment paradigm for elderly patients with IDH mutant AML. However, the challenge of how to best incorporate these agents into standard practice remains. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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Open AccessReview Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia
Cancers 2018, 10(6), 179; https://doi.org/10.3390/cancers10060179
Received: 1 May 2018 / Revised: 30 May 2018 / Accepted: 1 June 2018 / Published: 4 June 2018
Cited by 1 | PDF Full-text (526 KB) | HTML Full-text | XML Full-text
Abstract
Acute myeloid leukemia (AML) is a disease that affects adults aged 65 years and above, and survival in this population is poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for these patients but is underutilized due to frequent comorbidities and [...] Read more.
Acute myeloid leukemia (AML) is a disease that affects adults aged 65 years and above, and survival in this population is poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for these patients but is underutilized due to frequent comorbidities and perceived higher risk of treatment-related mortality and non-relapse mortality. Increasing data supports the utility of allo-HCT in fit older patients after intensive chemotherapy resulting in improvement of outcomes. With the development of reduced intensity and non-myeloablative conditioning regimens that are associated with lower rates of treatment-related toxicity and mortality, this has allowed more older patients with AML to receive allo-HCT. In this review, we provide some guidance on appropriate selection of older patients as transplant candidates, benefits and risks associated with allo-HCT, conditioning regimen choice, and stem cell transplant sources as they relate to the conduct of stem cell transplantation in older patients. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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Open AccessFeature PaperReview Beyond the Edge of Hypomethylating Agents: Novel Combination Strategies for Older Adults with Advanced MDS and AML
Cancers 2018, 10(6), 158; https://doi.org/10.3390/cancers10060158
Received: 24 April 2018 / Revised: 19 May 2018 / Accepted: 21 May 2018 / Published: 24 May 2018
Cited by 1 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text
Abstract
Higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) of the elderly exhibit several commonalities, including first line treatment with hypomethylating agents (HMA) like azacitidine (AZA) or decitabine (DAC). Until today, response to treatment occurs in less than 50 percent of patients, and [...] Read more.
Higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) of the elderly exhibit several commonalities, including first line treatment with hypomethylating agents (HMA) like azacitidine (AZA) or decitabine (DAC). Until today, response to treatment occurs in less than 50 percent of patients, and is often short-lived. Moreover, patients failing HMA have a dismal prognosis. Current developments include combinations of HMA with novel drugs targeting epigenetic or immunomodulatory pathways. Other efforts focus on the prevention of resistance to HMA using checkpoint inhibitors to enhance immune attack. This review focuses on recent advances in the field of HMA-based front-line therapies in elderly patients with myeloid diseases. Full article
(This article belongs to the Special Issue Treatment of Older Adults with Acute Myeloid Leukemia)
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