Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction
|
|
- Shon Harrington
- 6 years ago
- Views:
Transcription
1 INFORMED DECISIONS IN ACUTE MYELOID LEUKEMIA: BEYOND MORPHOLOGY AND CYTOGENETICS Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction Arati V. Rao Clinical Research, Hematology-Oncology, Gilead Sciences, Inc., Foster City, CA 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. Learning Objectives To review methods for assessing patient fitness by using available evidence that may guide the treatment of older patients with AML To recognize the importance of an individualized treatment approach outside of simple chronological age, along with the importance of clinical trials in this demographic accounting for the heterogeneity of both tumor biology and patient characteristics Introduction Acute myeloid leukemia (AML), the most common acute leukemia, is a disease of older adults, presenting at a median age of 68 years. Older patients are generally undertreated, and although selected older adults may benefit from intensive therapies, as a group, they experience increased treatment-related mortality and morbidity, have lower complete remission (CR) rates, are more likely to relapse, and have decreased survival. 1 Age-related outcome disparities are attributed to both tumor and host characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronological age alone. Patients can be matched with the right therapy with the help of both disease-specific risk factors (eg, karyotype and genetic mutations) and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. 2 Patient profiles, treatment patterns, and outcomes among elderly AML patients The most recent big data analysis consisted of a retrospective cohort analysis of primary AML patients older than age 66 years in the Surveillance, Epidemiology, and End Results (SEER) Medicare database from 2000 to In all, 3327 patients (40%) received chemotherapy within 3 months of diagnosis. The patients who received therapy were more likely to be younger, male, and married and were less likely to have secondary AML and poor performance indicators and comorbidity score compared with their untreated counterparts. In multivariate analysis (MVA), the 30-day mortality was 33% lower for the treated (9%) compared with the untreated (31%) group. Both intensive and hypomethylating agent (HMA) therapies compared with no therapy led to a significant survival benefit. In addition, younger Medicare patients were noted to have a survival benefit with allogeneic hematopoietic stem cell transplantation (HSCT). That study confirmed what has been known in the literature for at least the last 2 decades regarding AML in the elderly: that despite a known survival benefit with antileukemic therapy, about 60% of elderly AML patients remain untreated after diagnosis. However, treatment rates increased over the time period of the study from 35% in 2000 to 50% in Another similar analysis of treatment patterns, survival, and costs in elderly patients with primary AML used SEER data between 1997 and In that study, 43% of the 4058 patients received chemotherapy, and 57% received supportive care only. Among patients who received chemotherapy, 69% died within 1 year, and median survival was 7.0 months. Among patients who received supportive care only, 95.0% died within 1 year, and median survival was 1.5 months. Patient age and Charlson Comorbidity Index (CCI) score were directly proportional to receipt of chemotherapy and mortality. The mean all-cause health care cost per older AML patient was $96 078, the largest component of which was utilization of inpatient care and services (76.3%). Conflict-of-interest disclosure: The author is an employee of and has equity ownership in Gilead Sciences. Off-label drug use: None disclosed. Hematology
2 Another single-center study compared the direct costs of decitabine and conventional induction therapy in patients with AML (age older than 60 years) by using a semi-markov model that compiled survival and cost data. 5 The estimated cost of a direct hospital stay of 1 day was ~$2100, and the cost of an infusion clinic visit was ~$524. The cost-effectiveness was assessed by using an incremental costeffectiveness ratio. The expected cost was nearly the same in both groups, with $ for patients receiving cytarabine plus daunorubicin vs $ for patients who received decitabine alone. The incremental cost-effectiveness ratio per quality-adjusted life year with decitabine was $ It is important to note that the data accounted for re-induction therapy with idarubicin, fludarabine, cytarabine, and granulocyte colony-stimulating factor and consolidation therapy with 4 cycles of high-dose cytarabine. Quality of life in elderly AML patients Quality of life (QOL) is another very important outcome for the older AML patient, and it has been addressed in several studies. One study investigated the association between baseline QOL and physical function (PF) with short-term treatment outcomes in 239 adult and elderly AML patients treated with intensive chemotherapy (IC). 6 Sixty-day mortality, intensive care unit admission, and CR occurred in 9 (3.7%), 15 (6.3%), and 167 (69.9%) patients, respectively. QOL and PF at presentation were not predictive of 60-day mortality, intensive care unit admissions, or CR rates. Findings were similar when patients age 60 years or older were examined, thus suggesting that QOL at presentation in an elderly AML patient is likely a result of the disease itself and may not reflect the prediagnosis QOL. Another study from the same institution recruited 237 patients (97 were older than age 60 years) to study whether survivors of AML in remission after IC achieved significant improvements in QOL, fatigue, and PF over time. 7 One-year survival was 60% in older patients, and for patients in remission, global QOL, fatigue, certain physical performance measures, and daily function improved significantly over time. Clearly, choosing the right older AML patient for therapy on the basis of disease biology and host-related factors is becoming more important and may lead to better patient outcomes along with a decrease in health care related costs. Value of performance status in AML Performance status (PS) tools, such as Karnofsky performance status (KPS) or Eastern Cooperative Oncologic Group (ECOG) PS, are central to cancer care and to attempts to quantify the general wellbeing of patients with cancer to determine whether they can receive chemotherapy safely. Good PS is defined as a KPS $80% or an ECOG PS,2. In AML, age at diagnosis and ECOG PS correlate with 30-day induction mortality as demonstrated in a now landmark trial by the Southwest Oncology Group. 8 In that study (n 5 968), patients with ECOG PS of 0 had a 30-day mortality of 11% to 15% irrespective of age (ie, 56 to 65 years or older than 75 years). However, the mortality rate was 50% in patients older than age 75 years with ECOG PS 2 and was 82% for those with ECOG PS 3. Assessing PS is extremely subjective, and it is not always synonymous with functional status. Functional status is defined as the level of autonomy individuals have in their daily activities. The Activity Daily Living (ADL) scale and Instrumental Activity of Daily Living (IADL) scale are complementary tools that have been widely validated to measure functional status. In 1 small study of elderly AML patients (n 5 63), it was demonstrated that impairment according to the IADL scale was the single most predictive variable for median survival, even higher than age and unfavorable cytogenetics. 9 Thus, measuring function according to the IADL scale adds information to the KPS and may aid in identifying vulnerable patients. In addition to PS, another important factor that affects treatment decision making in older patients is comorbidity. Comorbidity is typically measured by using standardized indices to assess burden and severity of diseases; the most commonly used indices are the CCI and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI). 10,11 One study that used SEER claims that data from 5480 AML patients (median age, 78 years) demonstrated that although half of all patients had a favorable CCI score of 0, the score progressively worsened with age. 12 Patients age 65 to 69 years with a CCI score of 0 received leukemia therapy more than 3 times more often than patients age 80 years or older with the same CCI score. A recent single-institution study analyzed AML patients receiving IC between 2002 and 2009: 144 patients age 60 years or older and 133 patients younger than age 60 years. 13 Older patients had a worse survival and a higher comorbidity burden (CCI score $1, 58% vs 26%; P,.001). Prevalent comorbid conditions differed by age (diabetes, 19.2% vs 7.5%; cardiovascular disease, 12.5% vs 4.5% for older vs younger patients, respectively). The CCI was not independently associated with overall survival (OS) or 30-day mortality in either age group. Interestingly, among older patients, diabetes was associated with higher 30-day mortality (33.3% vs 12.0% in diabetic vs nondiabetic patients; P 5.006). After, controlling for age, cytogenetic, and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 times in older patients receiving IC. The HCT-CI is used in the transplant setting and has been studied in AML patients. 11 In 1 study of 177 patients age 60 years or older who received induction chemotherapy, the HCT-CI scores of 0, 1 to 2, and $3 corresponded to early death rates of 3%, 11%, and 29%, respectively and OS of 45, 31, and 19 weeks, respectively. 14 In another study of 92 AML patients age 80 years or older who had AML, 64% were treated intensively with a variety of regimens. 15 In that population of very elderly AML patients, the CCI and the HCT- CI had similar predictive ability for outcome in both groups. Thus, screening for comorbidities should be considered routine clinical practice and should be included in clinical trials as part of the inclusion and exclusion criteria. Integration of PS and comorbidity with other host-related factors may provide a better understanding of the AML patient as a whole and help individualize therapy for this patient population. Prognostic models and risk assessment Clinical trial data have been used to create algorithms to improve risk stratification of elderly AML patients. A variety of prognostic models have provided a wide range of estimates for early mortality (16% to 71%), CR (12% to 91%), and 3-year survival (3% to 40%) in older AML patients who receive intensive induction therapy One model for predicting OS identified age, karyotype, NPM1 mutational status, white blood cell count, lactate dehydrogenase levels, and CD4 expression as risk factors, and it categorized patients into 4 groups, with 3-year OS ranging from 3% to 40%. 16 Another model derived from.1000 intensively treated patients identified cytogenetic risk group, white blood cell count, secondary AML, PS, and age as predictors of OS. 17 One Web-based model predicting remission rates and induction mortality used clinical and laboratory variables (body temperature, age, hemoglobin, platelet count, secondary leukemia or antecedent hematologic disease, fibrinogen, and lactate dehydrogenase) and predicted CR rates ranging from 12% to 91%. 18 To predict 8-week induction mortality for patients age 70 years or older, another model included age 80 years or older, complex cytogenetics, ECOG PS.1, and creatinine.1.3 mg/dl. 19 Patients with risk factors of 0, 1, 2, and $3 had 8-week mortality rates of 16%, 31%, 340 American Society of Hematology
3 Table 1. Domains for cancer-specific comprehensive geriatric assessment Domain with measure No. of items Description Functional status MOS physical health 10 Measures limitations in a wide range of physical functions from bathing and dressing to vigorous activities such as running Instrumental Activities of Daily Living (subscale of the OARS) 7 Measures ability to complete activities required to maintain independence in the community (ie, preparing meals, shopping, making telephone calls, managing money) 1 Global indicator of patient function determined by the health care professional on a scale of 0 to 100 Karnofsky performance status (rated by the health care professional) No. of falls in the last 6 months 1 No. of times patient has fallen in the last 6 months Timed up and go 1 Performance-based measure of functional status: amount of time it takes for seated patient to rise from a chair, walk 10 feet, walk back, and sit down MOS social activities 4 Measures ability to participate in social activities and degree to which health status limits normal social activities Comorbid medical conditions Physical health section (subscale of the OARS) 15 List of comorbid illnesses and the degree to which they impair daily activities; patient can add additional comorbid illnesses not listed; rating of eyesight and hearing Psychological state Hospital Anxiety and Depression Scale 14 Measures of anxiety and depression Social support MOS social support survey: emotional information and tangible subscales 12 Perceived availability of social support Nutritional status Body mass index 1 Weight and height Percent unintentional weight loss in the past 6 months 1 Unintentional weight loss in last 6 months/baseline body weight Cognition Blessed Orientation-Memory-Concentration test 6 Gross measure of cognitive function Medications Comprehensive list of medications 1 List of medications including prescribed, herbal, and overthe-counter MOS, Medical Outcomes Study; OARS, Older Americans Resources and Services [Program]. 55%, and 71%, respectively. Although each of these models provides the treating oncologist with valuable information and aids decision making, they all rely on tumor characteristics and chronological age. None of these models incorporate the functional, cognitive, or psychosocial factors that are integral to aging. In addition, none of these models are designed to address end points that perhaps are relevant to older AML patients: QOL, days of hospitalization, PF, and rehabilitation or long-term care requirements. Comprehensive geriatric assessment: the case for the obvious Comprehensive geriatric assessment (CGA) is a tool used by geriatricians to assess functional status, comorbidity, cognition, social support system, nutrition, and medication use. 20 Results from the CGA can help oncologists predict outcomes and select appropriate therapy for their patients. CGA can also help identify and follow up on symptoms in older patients that can affect QOL. The first studies of CGA in older patients with cancer have been around for more than a decade. 20,21 Each domain within the CGA has been shown to predict morbidity and mortality in community-dwelling older adults (Table 1). Dependence for ADLs and IADLs is predictive of mortality in geriatric oncology, and the incidence of ADL and IADL deficiencies is higher for older patients with cancer than for agematched controls. The geriatrics literature supports the use of a directly observed assessment of PF to assess the risk of falls and identify vulnerability in older patients who may otherwise seem fit. 22,23 Other geriatric issues like polypharmacy, weight loss, cognitive disorders, depression, and social isolation can increase the risk of adverse events from chemotherapy in the older patient with cancer. A recent systematic review evaluated the value of geriatric assessment (GA) in elderly patients with hematologic malignancies in 15 studies; 3 of those studies were in AML patients. 24 The median age of patients was 73 years, and despite generally good PS, the prevalence of geriatric impairments was high. Geriatric impairments were noted in IADLs in 55%, nutritional status in 67%, cognitive Hematology
4 capacities in 83%, and objectively measured physical capacity in 100% of patients, all associated with a shorter OS in a relevant proportion of studies. Comorbidity, physical capacity, and nutritional status were more significantly and frequently predictive of toxicity and mortality than were age and PS. Table 2 summarizes 3 studies of CGA in older patients with AML One multi-institution study (n 5 195; median age, 71 years) assessed patients age 60 years or older with myelodysplastic syndrome and AML who were grouped according to treatment intensity (nonintensive, n 5 107; IC/HSCT, n 5 75) and who underwent GA. 25 GA consisted of 8 instruments that evaluated ADLs, depression, mental functioning, mobility, comorbidities, KPS, and QOL. Patients who received IC/HSCT were younger and significantly less often affected by geriatric symptoms. To focus on a homogenous cohort and to avoid the confounding effect of treatment, the authors conducted the GA only in patients who were not treated intensively (n 5 107). After MVA, a prognostic model was created that included disease-related factors such as poor risk cytogenetics and bone marrow blasts along with GA/QOL factors such as KPS, ADL, and fatigue; and it was noted that these factors were independently associated with OS in patients who received nonintensive therapy. Three GA variables (KPS, ADL, and fatigue) were used to create a risk score that correlated with OS. Patients who were low risk (0 risk features), intermediate risk (1 to 2 features), or high risk (all 3 features) had a median OS of 774, 231, or 51 days, respectively (P,.001). Another study in 101 patients age 65 years or older with newly diagnosed AML explored whether GA variables in addition to known prognostic factors predicted mortality. 26 Baseline comorbidity score, difficulty with strenuous activity, and pain were independent prognostic factors for greater risk of death after MVA that included the cytogenetic risk group. They remained independent predictors, even in the subset of patients with baseline ECOG PS 0 to 1, confirming the notion that GA adds value to traditional PS measurement. Is GA feasible in the inpatient setting? This question was answered by a small pilot study in 54 AML patients age 60 years or older who were receiving induction chemotherapy. 27 Ninety-three percent of this cohort completed the entire GA battery (ie, the modified Mini- Mental State Examination, Center for Epidemiologic Studies Depression Scale, Distress Thermometer, Pepper Assessment Tool for Disability [self- reported ADLs], instrumental ADLs, mobility questions, the Short Physical Performance Battery [SPPB, which includes timed 4-minute walk, chair stands, standing balance], grip strength, and HCT-CI) in a mean time of minutes. Interestingly, in this study, for the 38 patients who rated their PS as good (ie, ECOG #1), impairments in individual GA measures ranged from 23.7% to 50%. This pilot exploratory study highlighted two poignant issues. First, patients with more aggressive tumor biology had more depressive symptoms and poorer self-reported PF, which may reflect the emotional and physical consequences of rapidly progressive symptoms. Second, a broad range of cognitive, psychological, and physical function was found despite stratification according to cytogenetic risk group. The same authors further evaluated the predictive value of GA on OS in older AML patients (n 5 74; median age, 70 years) admitted to the inpatient service for IC. 28 Pretreatment GA included evaluation of cognition, depression, distress, PF (self-reported and objectively measured), and comorbidity. Objective PF was assessed using the SPPB (timed 4-minute walk, chair stands, standing balance) and grip strength. OS was significantly shorter for participants who screened positive for impairment in cognition and objectively measured PF after adjusting for several other patient and disease-related factors. In addition, the study highlighted the importance of GA and noted that SPPB was a better predictor of treatment outcome than recalled functional status, which supports the investigation of interventions to target physical vulnerability. Despite all this emerging data, there is no firm recommendation regarding which GA should be incorporated into clinical practice, at what time points during the treatment trajectory GA should be performed, and how to use that information to have a positive impact on the patient. Although GA can be conducted by a nurse or physician extender, it is time-consuming and requires additional personnel to perform. Will consultations based on GA findings have an impact on survival and QOL? If elderly AML patients who have poor PF are referred to physical therapy, or patients with underlying depression are offered psychotherapy, or patients with weight loss are referred to a nutritionist, will these recommendations lead to better outcome and lower mortality? These are all important questions that need to be addressed in future clinical trials. At this time, there is no evidence from a formal randomized controlled trial that compares induction therapy with IC to an HMA in the elderly patient with AML. In addition, there is no consensus on the role, choice, or value of postremission therapy in this patient population. Figure 1 provides a general algorithm on how the treating oncologist may combine measures of GA and AML biology 28 to aid in treatment decision making, but readers should be cautioned to make thoughtful choices for each elderly AML patient they encounter. Biomarkers of fitness: evaluating the physiologic reserve The elderly AML patient who commits to IC, HMA, or allogeneic HSCT has several reasons for a progressive decline in functional reserve that may lead to significant morbidity and mortality. Figure 2 illustrates how the interaction between the older host, underlying AML, and treatment effects can lead to loss of homeostasis and mortality. CGA can provide information on the general health status of individuals but is far from perfect as a prognostic or predictive tool for individual patients. Are there genomic and proteomic markers of aging that can help predict fitness in an elderly AML patient? 29 It is well known that aging is associated with numerous events at the molecular, cellular, and physiological levels that increase susceptibility to carcinogens, promote carcinogenesis, and decrease protective mechanisms. 30 In addition, cellular senescence, loss of function of tumor suppressor genes, and excessive exposure of the cell to oxidative stress can also lead to a similar response to that observed with replicative exhaustion, resulting in a permanently growth-arrested senescent status. 31 Telomere length and telomerase activity, gene expression of aging related genes, and plasma microrna expression are all potential biomarkers of aging. 32 Lymphocyte senescence, 33 and thus aging of the immune system, is reflected by increased messenger RNA expression of the cell cycle regulator p16 INK4a. In addition, inflammaging (ie, inflammation in the process of aging) has been well studied in AML, and activation of pro-inflammatory cytokines (eg, interleukin-6 [IL-6], tumor necrosis factor a [TNF-a], and IL-8) and chemokines can alter the disease course, affect the bone marrow microenvironment, and play a deleterious role in the progression of AML. 34 The geriatric host is particularly vulnerable as these cytokines and chemokines are also implicated in the development of frailty, fatigue, and declining cognitive function. One study has examined the relationship between circulating cytokines and 342 American Society of Hematology
5 Table 2. Studies in older AML adults using CGA Reference Disease and no. of patients Therapy Variables Outcomes: impact on OS Clinical Disease Treatment CGA variables Risk groups OS P 25 MDS (n 5 63) AML (n 5 132) Non-IC* (n 5 120); IC (n 5 65) BM blast.20%, cytogenetics, HCT-CI $3 KPS,80, impaired ADLs (Barthel index.100), high fatigue score (EORTC QLQ- C30 $50) Low risk (0 risk features) Intermediate risk (1 to 2 risk features) High risk (3 risk features) 744 d 231 d 51 d, AML (n 5 74) IC Hemoglobin, age, sex, ECOG PS, cytogenetics Prior MDS Cognitive impairment (CI) (Modified MMSE, 77), impaired PF (SPPB,9) CI vs no CI 5.2 vs 15.6 mo.002 Impaired PF vs 6 vs 16.8 mo.018 not impaired PF 26 AML (n 5 101) Non-IC* (n5 65); IC (n 5 35) Age.72 y, ECOG PS.1, cytogenetics, HCT-CI.1 Secondary AML CR; allogeneic HSCT Strenuous activity difficulty, pain (more often vs less often) Less vs more difficulty with strenuous activity 11.8 vs 4.4 mo,.001 Less vs more pain 1.3 vs 4.1 mo,.002 HCT-CI score 11.8 vs 4.4 mo,.001 #1 vs.1 BM, bone marrow; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30; MDS, myelodysplastic syndrome; MMSE, Mini-Mental State Examination. *Non-IC includes best supportive care, HMAs such as decitabine and azacitidine, and other agents such as single-agent 6-mercaptopurine. Hematology
6 Figure 1. Proposed algorithm for treating the elderly AML patient. 3MS, 100-point Modified Mental State Examination. cancer-related fatigue in 74 older AML patients before and after the first cycle of induction chemotherapy. 35 Plasma levels of 13 cytokines were measured via electrochemiluminescence. At baseline, clinically significant correlations were seen between TNF-a and fatigue. Over time, correlations with fatigue were noted with TNF-a, and the chemokine interferon-inducible protein 10 (IP-10). The European Organisation for Research and Treatment of Cancer (EORTC) Elderly Task Force (ETF) has initiated an aging biomarker program. Biological material will be collected in patients participating in EORTC-ETF clinical trials. Candidate biomarkers cover different aspects of the biology of aging and include leukocyte telomere length, p16 INK4a expression in T lymphocytes, immunosenescence markers, oxidative stress markers, circulating inflammatory mediators, genetic variability in aging- and longevity-related genes, and microrna expression. The purpose of this program is to evaluate the feasibility of this approach and validate the ability of this panel of candidate aging biomarkers to determine a person s biological age, provide important information on life expectancy, and determine the reserve capacities of patients as well as their chance of tolerating therapy or the risk of suffering severe toxicity. Future directions: exercise as an intervention and the concept of biological age It is evident that older AML patients benefit from therapy, be it IC, HMA, or even an allogeneic HSCT. How we assess fitness for the type of therapy prescribed is paramount. CGA, a time-tested measure adopted from geriatricians, clearly helps predict for OS in older patients with AML by identifying vulnerable patients as elucidated in the studies by Klepin et al. 28 There are several mechanisms by which impaired physical performance may lead to worse survival in AML 344 American Society of Hematology
7 Figure 2. Interaction between host, disease, and treatment-related factors. IFN-g, interferon gamma. and these include long periods of therapy leading to inactivity and immobility, increased risk of infectious complications, falls, and accelerated deconditioning that prohibits delivery of consolidation therapy needed for cure. The advice to rest and avoid intensive exercises is still common practice and is given, partly because of severe anemia and thrombocytopenia in this patient population. Exercise during and after chemotherapy could decrease risks associated with low physical performance at presentation and potentially improve outcomes. A Cochrane Database Systematic Review of aerobic exercise in adults with hematologic malignancies included 9 randomized controlled trials that involved 818 participants. 36 There were a fair number of AML studies, and the authors concluded that there is no evidence for differences in mortality between the exercise and control groups. Physical exercise added to standard care can improve QOL, especially physical functioning, depression, and fatigue. Currently, the evidence is inconclusive regarding anxiety, physical performance, adverse events, and serious adverse events. In the AML population, there have been a few small trials. One small pilot study of 40 patients age 40 years or older concluded that a home-based exercise program for posttreatment AML patients can be safely delivered with reasonable recruitment and high retention. 37 However, feasibility was hampered by low adherence. Another study enrolled 24 older adults with a mean age of 65 years who were hospitalized for AML chemotherapy. 38 Patients were enrolled in a 4-week exercise intervention that included stretching, walking, and strength exercises. Feasibility measures included recruitment, retention, and number of exercise sessions. Unlike the home-based exercise program, this inpatient exercise program demonstrated that 87.5% of participants completed baseline measures, 70.8% attended $1 exercise sessions, and 50.0% completed postintervention assessment. Among baseline characteristics, only higher physical performance was associated with a greater number of exercise sessions attended, and postintervention QOL and depressive symptoms improved as a result of the exercise. CGA in older AML patients leads to the discovery of a broad range of cognitive and psychological issues, and prior knowledge of this may have an impact on issues such as understanding and signing an informed consent for a clinical trial, timing and use of steroids as premedication, aiding caregivers, and the proactive use of psychotherapy and antidepressants. One study has demonstrated the utility of a clinico-genomic assessment of PS. 39 The authors used clinically annotated microarray data (messenger RNA expression from marrow leukemic blasts) from 2 data sets with 377 AML patients (GSE1159 and GSE12417). A frailty profile was developed by using a set of previously characterized gene sets and pathways that define the following cytokines: IL-6, IL-1, IL-2, TNF-a, and C-reactive protein. The frailty profile was then queried in the 377 AML patients and by unsupervised clustering methods, two cohorts (n 5 58) that represented extremes of survival (cohort 1: median survival, 4.9 months; cohort 2: median survival, 46.3 months; P,.001) were identified. OS for these 58 AML patients, based on clinical ECOG PS only, was not statistically significant (14 months for ECOG PS 0 to 1 and 8.8 months for ECOG PS 2 or greater; P 5.29). The authors further stratified these patients into 3 risk groups: low, intermediate, and high risk depending on a cohort based on its frailty profile and ECOG PS. This combined analysis revealed that low-risk patients (cohort 2 Hematology
8 plus ECOG PS 0 to 1) had a statistically significantly higher survival of 56.1 months compared with intermediate-risk (9.85 months) and high-risk (8.35 months) patients; P This suggests that gene expression for cytokines from leukemic blasts does add information to a subjective clinical parameter such as the ECOG PS. Conclusions AML is a very heterogeneous malignancy and although the response rates to chemotherapy have increased over the past 3 decades, this improvement has been limited to patients age 65 to 74 years. Survival rates have not improved in patients age 75 years or older, and in the oldest old (the fastest growing segment of the US population [ie, patients age 85 years or older]), the survival rates are the lowest with no improvement over time. 40 Because the population is aging, we expect an increase in the incidence of AML. We hope that we can move past using only chronological age and instead use functional age and biological age to tailor the right therapy for each AML patient. In the future, clinical trials in elderly AML patients should perhaps be geriatricized to account for the heterogeneity of AML biology and the aging patient, and in addition, end points for trials should include outcomes addressing QOL, maintenance of independence, and use of health care services. Correspondence Arati V. Rao, Gilead Sciences, Inc., 333 Lakeside Dr, Foster City, CA 94404; arati.rao@gilead.com. References 1. National Cancer Institute. SEER Stat Fact Sheets: Acute Myeloid Leukemia. Bethesda, MD Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015;125(5): Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015; 94(7): Meyers J, Yu Y, Kaye JA, Davis KL. Medicare fee-for-service enrollees with primary acute myeloid leukemia: an analysis of treatment patterns, survival, and healthcare resource utilization and costs. Appl Health Econ Health Policy. 2013;11(3): Batty N, Wiles S, Kabalan M, et al. Decitabine is more cost effective than standard conventional induction therapy in elderly acute myeloid leukemia patients [abstract]. Blood. 2013;122(21). Abstract Timilshina N, Breunis H, Brandwein JM, et al. Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML? Ann Oncol. 2014;25(4): Alibhai SM, Breunis H, Timilshina N, et al. Quality of life and physical function in adults treated with intensive chemotherapy for acute myeloid leukemia improve over time independent of age. J Geriatr Oncol. 2015; 6(4): Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107(9): Wedding U, Röhrig B, Klippstein A, Fricke HJ, Sayer HG, Höffken K. Impairment in functional status and survival in patients with acute myeloid leukaemia. J Cancer Res Clin Oncol. 2006;132(10): Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11): Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8): Etienne A, Esterni B, Charbonnier A, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer. 2007;109(7): Tawfik B, Pardee TS, Isom S, et al. Comorbidity, age, and mortality among adults treated intensively for acute myeloid leukemia (AML). J Geriatr Oncol. 2016;7(1): Giles FJ, Borthakur G, Ravandi F, et al. The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. Br J Haematol. 2007;136(4): Harb AJ, Tan W, Wilding GE, et al. Treating octogenarian and nonagenarian acute myeloid leukemia patients predictive prognostic models. Cancer. 2009;115(11): Röllig C, Thiede C, Gramatzki M, et al; Study Alliance Leukemia. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood. 2010;116(6): Wheatley K, Brookes CL, Howman AJ, et al; United Kingdom National Cancer Research Institute Haematological Oncology Clinical Studies Group and Acute Myeloid Leukaemia Subgroup. Prognostic factor analysis of the survival of elderly patients with AML in the MRCAML11andLRFAML14trials.Br J Haematol. 2009;145(5): Krug U, Röllig C, Koschmieder A, et al; German Acute Myeloid Leukaemia Cooperative Group; Study Alliance Leukemia Investigators. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet. 2010;376(9757): Kantarjian H, Ravandi F, O Brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116(22): Hurria A, Gupta S, Zauderer M, et al. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer. 2005;104(9): Hurria A, Cirrincione CT, Muss HB, et al. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB J Clin Oncol. 2011;29(10): Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305(1): Studenski S, Perera S, Wallace D, et al. Physical performance measures in the clinical setting. J Am Geriatr Soc. 2003;51(3): Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy a systematic review. Leuk Res. 2014;38(3): Deschler B, Ihorst G, Platzbecker U, et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98(2): Sherman AE, Motyckova G, Fega KR, et al. Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9): Klepin HD, Geiger AM, Tooze JA, et al. The feasibility of inpatient geriatric assessment for older adults receiving induction chemotherapy for acute myelogenous leukemia. J Am Geriatr Soc. 2011;59(10): Klepin HD, Geiger AM, Tooze JA, et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood. 2013;121(21): Falandry C, Gilson E, Rudolph KL. Are aging biomarkers clinically relevant in oncogeriatrics? Crit Rev Oncol Hematol. 2013;85(3): Pallis AG, Hatse S, Brouwers B, et al. Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging? J Geriatr Oncol. 2014;5(2): Campisi J, Andersen JK, Kapahi P, Melov S. Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol. 2011;21(6): Townsley DM, Dumitriu B, Young NS. Bone marrow failure and the telomeropathies. Blood. 2014;124(18): Coppé JP, Rodier F, Patil CK, Freund A, Desprez PY, Campisi J. Tumor suppressor and aging biomarker p16(ink4a) induces cellular senescence 346 American Society of Hematology
9 without the associated inflammatory secretory phenotype. J Biol Chem. 2011;286(42): Nipp RD, Rao AV. Performance status in elderly patients with acute myeloid leukemia: exploring gene expression signatures of cytokines and chemokines. J Gerontol A Biol Sci Med Sci. 2015;70(6): Fung FY, Li M, Breunis H, Timilshina N, Minden MD, Alibhai SM. Correlation between cytokine levels and changes in fatigue and quality of life in patients with acute myeloid leukemia. Leuk Res. 2013;37(3): Bergenthal N, Will A, Streckmann F, et al. Aerobic physical exercise for adult patients with haematological malignancies. Cochrane Database Syst Rev. 2014;11(11):CD Alibhai SM, O Neill S, Fisher-Schlombs K, et al. A pilot phase II RCT of a home-based exercise intervention for survivors of AML. Support Care Cancer. 2014;22(4): Klepin HD, Danhauer SC, Tooze JA, et al. Exercise for older adult inpatients with acute myelogenous leukemia: A pilot study. J Geriatr Oncol. 2011;2(1): Rao A, Acharya C, Cohen HJ, Rizzieri D, Potti A. A clinico-genomic model of performance status in acute myeloid leukemia [abstract]. J Clin Oncol. 28:15s, 2010 (suppl). Abstract Thein MS, Ershler WB, Jemal A, Yates JW, Baer MR. Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer. 2013;119(15): Hematology
OF LIFE AMONG OLDER ADULTS WITH HEMATOLOGIC MALIGNANCIES
GERIATRIC ASSESSMENT AND QUALITY OF LIFE AMONG OLDER ADULTS WITH HEMATOLOGIC MALIGNANCIES Daneng Li, MD Assistant Clinical Professor Medical Oncology & Therapeutics Research Erin Kopp M.S.N, A.C.N.P-B.C.,
More informationGetting Fit for Transplant. Thuy Koll, MD Assistant Professor Division of Geriatrics Department of Internal Medicine
Getting Fit for Transplant Thuy Koll, MD Assistant Professor Division of Geriatrics Department of Internal Medicine No Disclosures. Objectives Describe frailty in transplant Discuss the role of physical
More informationBackground CPX-351. Lancet J, et al. J Clin Oncol. 2017;35(suppl): Abstract 7035.
Overall Survival (OS) With Versus in Older Adults With Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia (taml): Subgroup Analysis of a Phase 3 Study Abstract 7035 Lancet JE, Rizzieri D, Schiller
More informationNew treatment strategies in myelodysplastic syndromes and acute myeloid leukemia van der Helm, Lidia Henrieke
University of Groningen New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia van der Helm, Lidia Henrieke IMPORTANT NOTE: You are advised to consult the publisher's version
More informationAssessing older patients with hematological malignancies
Assessing older patients with hematological malignancies Alfonso J. Cruz Jentoft Servicio de Geriatría Hospital Universitario Ramón y Cajal Madrid, Spain Is old = frail? 45 days old 2,000 years old 4,600
More informationN Engl J Med Volume 373(12): September 17, 2015
Review Article Acute Myeloid Leukemia Hartmut Döhner, M.D., Daniel J. Weisdorf, M.D., and Clara D. Bloomfield, M.D. N Engl J Med Volume 373(12):1136-1152 September 17, 2015 Acute Myeloid Leukemia Most
More informationGeriatric Assessment to Improve Outcomes for Older Adults with Cancer
Geriatric Assessment to Improve Outcomes for Older Adults with Cancer Allison Magnuson, DO Assistant Professor of Medicine University of Rochester Medical Center Objectives Appreciate the demographics
More informationSingle Technology Appraisal (STA) Midostaurin for untreated acute myeloid leukaemia
Single Technology Appraisal (STA) Midostaurin for untreated acute myeloid leukaemia Response to consultee and commentator comments on the draft remit and draft scope (pre-referral) Please note: Comments
More informationGeriatric screening tools in older patients with cancer
Geriatric screening tools in older patients with cancer Pr. Elena Paillaud Henri Mondor hospital, Créteil, France University Paris-Est Créteil CONFLICT OF INTEREST DISCLOSURE I have the following potential
More informationIntegrating Geriatrics into Oncology Care
Integrating Geriatrics into Oncology Care William Dale, MD, PhD Chief, Geriatrics & Palliative Medicine Director, Specialized Oncology Care & Research in the Elderly (SOCARE) Clinic University of Chicago
More informationCorporate Medical Policy. Policy Effective February 23, 2018
Corporate Medical Policy Genetic Testing for FLT3, NPM1 and CEBPA Mutations in Acute File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_flt3_npm1_and_cebpa_mutations_in_acute_myeloid_leukemia
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 3,800 116,000 120M Open access books available International authors and editors Downloads Our
More informationDr. Joyita Banerjee PhD Scholar Dept. of Geriatric Medicine AIIMS, New Delhi, India
IMPORTANCE OF COMPREHENSIVE GERIATRIC ASSESSMENT IN CANCER IN ELDERLY AN INDIAN PERSPECTIVE Dr. Joyita Banerjee PhD Scholar Dept. of Geriatric Medicine AIIMS, New Delhi, India INTRODUCTION - Cancer in
More informationAcute Myeloid Leukemia
Acute Myeloid Leukemia Pimjai Niparuck Division of Hematology, Department of Medicine Ramathibodi Hospital, Mahidol University Outline Molecular biology Chemotherapy and Hypomethylating agent Novel Therapy
More informationRemission induction in acute myeloid leukemia
Int J Hematol (2012) 96:164 170 DOI 10.1007/s12185-012-1121-y PROGRESS IN HEMATOLOGY How to improve the outcome of adult acute myeloid leukemia? Remission induction in acute myeloid leukemia Eytan M. Stein
More informationReference: NHS England 1602
Clinical Commissioning Policy Proposition: Clofarabine for refractory or relapsed acute myeloid leukaemia (AML) as a bridge to stem cell transplantation Reference: NHS England 1602 First published: TBC
More informationPERFORMANCE AFTER HSCT Mutlu arat, md ıstanbul bilim un., dept. hematology ıstanbul, turkey
PERFORMANCE AFTER HSCT Mutlu arat, md ıstanbul bilim un., dept. hematology ıstanbul, turkey Joint Educational Meeting of the EBMT Severe Aplastic Anaemia, Late Effects and Autoimmune Diseases Working Parties
More informationScottish Medicines Consortium
Scottish Medicines Consortium azacitidine 100mg powder for suspension for injection (Vidaza ) No. (589/09) Celgene Ltd 05 March 2010 The Scottish Medicines Consortium (SMC) has completed its assessment
More informationWhat is New in Geriatric Oncology: The Medical Oncology Perspective. Arti Hurria, MD Director, Cancer and Aging Research Program City of Hope
What is New in Geriatric Oncology: The Medical Oncology Perspective Arti Hurria, MD Director, Cancer and Aging Research Program City of Hope Cancer Incidence in the U.S. Between 2010 and 2030, cancer incidence
More information22th March Endpoints and their relevance to older people: Cancer and Palliative Care and work of EORTC. Ulrich Wedding
22th March 2012 Endpoints and their relevance to older people: Cancer and Palliative Care and work of EORTC Elderly Task Force EORTC, Brussels University of Jena, Germany Department of Palliative Care
More informationComorbidities in Multiple Myeloma
Comorbidities in Multiple Myeloma Michel Delforge, MD, PhD University Hospital Leuven Leuven, Belgium COMy, Bangkok 12 may 2014 Comy Meeting, Bangkok, 12 may 2014 Disclosures Advisory board: Janssen,
More informationCytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia
Acute Myeloid Leukemia Articles Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia Bruno C. Medeiros, 1 Megan Othus, 2,3 Min Fang, 3,4 Frederick R. Appelbaum,
More informationTreating for Cure or Palliation: Difficult Decisions for Older Adults with Lymphoma
Treating Frail Adults With Common Malignancies: Best Evidence to Personalize Therapy Treating for Cure or Palliation: Difficult Decisions for Older Adults with Lymphoma Raul Cordoba, MD, PhD Lymphoma Unit
More information4/26/2012. Laura Grooms, MD Assistant Professor Geriatric Medicine Department of Family and Geriatric Medicine University of Louisville April 20, 2012
Laura Grooms, MD Assistant Professor Geriatric Medicine Department of Family and Geriatric Medicine University of Louisville April 20, 2012 Laura Grooms, MD Assistant Professor Geriatric Medicine Department
More informationRehabilitation of the Older Cancer Patient. Lodovico Balducci, M.D. Moffitt Cancer Center Tampa, Florida
Rehabilitation of the Older Cancer Patient Lodovico Balducci, M.D. Moffitt Cancer Center Tampa, Florida Rehabilitation of the older cancer patient Is cancer treatment effective in older individuals? Chronologic
More informationBiologic vs physiologic age in the transplant candidate
BONE MARROW TRANSPLANT: UNDERSTANDING AND IMPROVING THE RISK-BENEFIT RATIO Biologic vs physiologic age in the transplant candidate Andrew S. Artz Section of Hematology/Oncology, Department of Medicine,
More informationWorkshop I: Patient Selection Current indication for HCT in adults. Shinichiro Okamoto MD, PhD Keio University, Tokyo, Japan
Workshop I: Patient Selection Current indication for HCT in adults Shinichiro Okamoto MD, PhD Keio University, Tokyo, Japan Factors to Take into Account with Recommending HCT Patient & disease factors
More informationImproving the Survivorship of Older Adults with Cancer Using Geriatric Assessment
Improving the Survivorship of Older Adults with Cancer Using Geriatric Assessment Deborah Bacon, RN,BSN Geriatric Oncology Clinical Nurse Coordinator James P Wilmot Cancer Institute Outline Geriatric assessment
More informationLeukemia. Andre C. Schuh. Princess Margaret Cancer Centre Toronto
Leukemia Andre C. Schuh Princess Margaret Cancer Centre Toronto AGENDA Ø Overview Ø Key News This Year Ø Key News out of ASH 2016 Sessions Abstracts Ø Canadian Perspective Ø Overview 2015- Stone, R. et
More informationThe SOCARE Model of Cancer Care for Older Adults: Building Infrastructure and Policies for Truly Personalized Cancer Care for an Aging Society
The SOCARE Model of Cancer Care for Older Adults: Building Infrastructure and Policies for Truly Personalized Cancer Care for an Aging Society William Dale, MD, PhD Michael M Davis Lecture Series University
More informationTREATMENT CONSIDERATIONS IN CLL/SLL AND FL. June 6, 2018
TREATMENT CONSIDERATIONS IN CLL/SLL AND FL June 6, 2018 0 PRESENTATION OVERVIEW IN CLL/SLL AND FL: Discuss key considerations that influence patient outcomes Highlight the importance of patients quality
More informationKEY WORDS: CRp, Platelet recovery, AML, MDS, Transplant
Platelet Recovery Before Allogeneic Stem Cell Transplantation Predicts Posttransplantation Outcomes in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome Gheath Alatrash, Matteo Pelosini,
More informationTreating Higher-Risk MDS. Case presentation. Defining higher risk MDS. IPSS WHO IPSS: WPSS MD Anderson PSS
Treating Higher-Risk MDS Eyal Attar, M.D. Massachusetts General Hospital Cancer Center eattar@partners.org 617-724-1124 Case presentation 72 year old man, prior acoustic neuroma WBC (X10 3 /ul) 11/08 12/08
More informationEvolving Targeted Management of Acute Myeloid Leukemia
Evolving Targeted Management of Acute Myeloid Leukemia Jessica Altman, MD Robert H. Lurie Comprehensive Cancer Center of Northwestern University Learning Objectives Identify which mutations should be assessed
More informationCLINICAL STUDY REPORT SYNOPSIS
CLINICAL STUDY REPORT SYNOPSIS Document No.: EDMS-PSDB-5412862:2.0 Research & Development, L.L.C. Protocol No.: R115777-AML-301 Title of Study: A Randomized Study of Tipifarnib Versus Best Supportive Care
More informationGeriatrics and Cancer Care
Geriatrics and Cancer Care Roger Wong, BMSc, MD, FRCPC, FACP Postgraduate Dean of Medical Education Clinical Professor, Division of Geriatric Medicine UBC Faculty of Medicine Disclosure No competing interests
More informationQuality of life beyond 6 months after diagnosis in older adults with acute myeloid leukemia
Critical Reviews in Oncology/Hematology 69 (2009) 168 174 Quality of life beyond 6 months after diagnosis in older adults with acute myeloid leukemia Shabbir M.H. Alibhai a,b,d,e,, Marc Leach a, Vikas
More informationShould lower-risk myelodysplastic syndrome patients be transplanted upfront? YES Ibrahim Yakoub-Agha France
Should lower-risk myelodysplastic syndrome patients be transplanted upfront? YES Ibrahim Yakoub-Agha France Myelodysplastic syndromes (MDS) are heterogeneous disorders that range from conditions with a
More informationDisrupting the Cell Cycle to Treat AML and MDS Rodman & Renshaw Conference
CYC 682 Disrupting the Cell Cycle to Treat AML and MDS Rodman & Renshaw Conference September 2014 Disclaimer This presentation contains forward-looking statements within the meaning of the safe harbor
More informationLAM 20-30% Cristina Papayannidis, MD, PhD DIMES, Istituto di Ematologia L. e A. Seràgnoli Università di Bologna
LAM 20-30% Cristina Papayannidis, MD, PhD DIMES, Istituto di Ematologia L. e A. Seràgnoli Università di Bologna FAB CLASSIFICATION OF MYELODYSPLASTIC SYNDROME Subtype % Blood Myeloblasts Bone Marrow Myeloblasts
More informationDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; 2 Sunesis Pharmaceuticals, Inc, South San Francisco
Phase I/II Study of Vosaroxin and Decitabine in Newly Diagnosed Older Patients with Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) Naval Daver 1, Hagop Kantarjian 1, Guillermo
More informationNew Approaches to Evaluate And Optimize Older Patients for Transplant (Allogeneic)
New Approaches to Evaluate And Optimize Older Patients for Transplant (Allogeneic) Andrew S. Artz, MD, MS Associate Professor of Medicine Clinical Director, Hematopoietic Cellular Therapy Program University
More informationNational Horizon Scanning Centre. Decitabine (Dacogen) for myelodysplastic syndrome. April 2008
Decitabine (Dacogen) for myelodysplastic syndrome April 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be
More informationFrailty in Older Adults. Farshad Sharifi, MD, MPH Elderly Health Research Center
Frailty in Older Adults Farshad Sharifi, MD, MPH Elderly Health Research Center 1 Outlines Definition of frailty Significance of frailty Conceptual Frailty Models Pathogenesis of frailty Management of
More informationAcute myeloid leukemia: prognosis and treatment. Dimitri A. Breems, MD, PhD Internist-Hematoloog Ziekenhuis Netwerk Antwerpen Campus Stuivenberg
Acute myeloid leukemia: prognosis and treatment Dimitri A. Breems, MD, PhD Internist-Hematoloog Ziekenhuis Netwerk Antwerpen Campus Stuivenberg Patient Female, 39 years History: hypothyroidism Present:
More informationTreating acute myeloid leukemia in older adults
ACUTE MYELOID LEUKEMIA IN THE ELDERLY PATIENT Treating acute myeloid leukemia in older adults Eunice S. Wang 1 1 Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY Acute
More informationAML in elderly. D.Selleslag AZ Sint-Jan Brugge, Belgium 14 December 2013
AML in elderly D.Selleslag AZ Sint-Jan Brugge, Belgium 14 December 2013 AML is predominantly a disease of the elderly incidence 2 3/100.000 SEER Cancer Statistics, National Cancer Institute, USA 2002 2006
More informationRisk stratification in the older patient; what are our priorities?
Risk stratification in the older patient; what are our priorities? Sonja Zweegman MD PhD Amsterdam The Netherlands Negative impact of age on survival Meta-analysis of European trials (MP vs MPT, VMP vs
More information39% Treated. 61% Untreated. 33% UnRx. 45% UnRx. 59% UnRx. 80% UnRx
AML in the Elderly สน น ว ส ทธ ศ กด ช ย งานประช มว ชาการกลางป สมาคมโลห ตว ทยาแห งประเทศไทย คร งท 53 25-26 ต ลาคม 2561 ณ โรงแรมเลอ เมอร เด ยน เช ยงใหม จ งหว ดเช ยงใหม 33% UnRx 45% UnRx 59% UnRx 80% UnRx
More information[ NASDAQ: MEIP ] Analyst & Investor Event December 8, 2014
[ NASDAQ: MEIP ] Analyst & Investor Event December 8, 2014 Forward-Looking Statements These slides and the accompanying oral presentation contain forward-looking statements. Actual events or results may
More informationBio-Path Announces Clinical Update to Interim Analysis of Phase 2 Prexigebersen Trial in Acute Myeloid Leukemia
Bio-Path Announces Clinical Update to Interim Analysis of Phase 2 Prexigebersen Trial in Acute Myeloid Leukemia Interim Data Update from Phase 2 Study Demonstrates Meaningful Clinical Improvement with
More informationThe Changing Face of MDS: Advances in Treatment
Thank you very much again for listening to me. We are going to be talking now in terms of therapy of MDS or The Changing Face of MDS Advances in Treatment. My name is Guillermo Garcia-Manero. I am a Professor
More informationIII. AML IN OLDER ADULTS: ARE WE LISTENING?
III. AML IN OLDER ADULTS: ARE WE LISTENING? Mikkael A. Sekeres, MD, MS* AML is a disease of older adults. In the US, the median age is 68 years and the age-adjusted population incidence is 17.6 per 100,000
More informationWhat is frailty and why it is important
What is frailty and why it is important Tony Moran North West Knowledge and Intelligence Team Cancer Outcomes Conference 2013 Contents Definitions of frail and frailty Prevalence and measurement Use in
More informationHCT for Myelofibrosis
Allogeneic HSCT for MDS and Myelofibrosis Sunil Abhyankar, MD Professor Medicine, Medical Director, Pheresis and Cell Processing University of Kansas Hospital BMT Program April 27 th, 213 HCT for Myelofibrosis
More informationManagement of the Frail Older Patients: What Are the Outcomes
Management of the Frail Older Patients: What Are the Outcomes Professor Edwina Brown Imperial College Renal and Transplant Centre Hammersmith Hospital, London Increasing prevalence of old old on RRT RRT
More informationHEMATOLOGIC MALIGNANCIES BIOLOGY
HEMATOLOGIC MALIGNANCIES BIOLOGY Failure of terminal differentiation Failure of differentiated cells to undergo apoptosis Failure to control growth Neoplastic stem cell FAILURE OF TERMINAL DIFFERENTIATION
More informationSafety and Efficacy of Venetoclax Plus Low-Dose Cytarabine in Treatment-Naïve Patients Aged 65 Years With Acute Myeloid Leukemia
Safety and Efficacy of Venetoclax Plus Low-Dose Cytarabine in Treatment-Naïve Patients Aged 65 Years With Acute Myeloid Leukemia Abstract 102 Wei AH, Strickland SA, Roboz GJ, Hou J-Z, Fiedler W, Lin TL,
More informationStem cell transplantation in elderly, but fit multiple myeloma patients
Stem cell transplantation in elderly, but fit multiple myeloma patients Mohamad MOHTY, MD, PhD Clinical Hematology and Cellular Therapy Dpt. Université Pierre & Marie Curie, Hôpital Saint-Antoine INSERM
More informationConcomitant WT1 mutations predicted poor prognosis in CEBPA double-mutated acute myeloid leukemia
Concomitant WT1 mutations predicted poor prognosis in CEBPA double-mutated acute myeloid leukemia Feng-Ming Tien, Hsin-An Hou, Jih-Luh Tang, Yuan-Yeh Kuo, Chien-Yuan Chen, Cheng-Hong Tsai, Ming Yao, Chi-Cheng
More informationmidostaurin should be extended to patients who are deemed fit to receive intensive induction and consolidation, regardless of age.
midostaurin should be extended to patients who are deemed fit to receive intensive induction and consolidation, regardless of age. perc deliberated on the toxicity profile of midostaurin and noted that
More informationUpdate: Chronic Lymphocytic Leukemia
ASH 2008 Update: Chronic Lymphocytic Leukemia Improving Patient Response to Treatment with the Addition of Rituximab to Fludarabine-Cyclophosphamide ASH 2008: Update on chronic lymphocytic leukemia CLL-8
More informationMyelodysplasia/Myeloproliferative Neoplasms (MDS/MPN) Post-HCT Data
Instructions for Myelodysplasia/Myeloproliferative Neoplasms (MDS/MPN) Post-HCT Data (Form 2114) This section of the CIBMTR Forms Instruction Manual is intended to be a resource for completing the Myelodysplasia/Myeloproliferative
More informationSuppor&ve care in older adults with haematological malignancies
Suppor&ve care in older adults with haematological malignancies Never too old the important role of exercise in older adults with caner Annual Mee&ng MASCC / ISOO, Vienna, June 29 th, 2018 Reinhard STAUDER
More informationBiol Blood Marrow Transplant 19 (2013) 429e434
Biol Blood Marrow Transplant 19 (2013) 429e434 Pilot Study of Comprehensive Geriatric Assessment (CGA) in Allogeneic Transplant: CGA Captures a High Prevalence of Vulnerabilities in Older Transplant Recipients
More informationSummary of Key AML Abstracts Presented at the European Hematology Association (EHA) June 22-25, 2017 Madrid, Spain
Summary of Key AML Abstracts Presented at the European Hematology Association (EHA) June 22-25, 2017 Madrid, Spain EHA 2017 ANNUAL MEETING: ABSTRACT SEARCH PAGE: https://learningcenter.ehaweb.org/eha/#!*listing=3*browseby=2*sortby=1*media=3*ce_id=1181*label=15531
More informationPre- Cardiac intervention. Dr. Victor Sim 26 th Sept 2014
Pre- Cardiac intervention Frailty assessment Dr. Victor Sim 26 th Sept 2014 Defining frailty Lacks consensus (Rockwood CMAJ 2005;173(5):489-95 Introduction) Some consider symptoms, signs, diseases and
More informationCytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia
Published Ahead of Print on December 19, 2014, as doi:10.3324/haematol.2014.117267. Copyright 2014 Ferrata Storti Foundation. Cytogenetic heterogeneity negatively impacts outcomes in patients with acute
More informationCharacteristics and Outcome of Therapy-Related Acute Promyelocytic Leukemia After Different Front-line Therapies
Characteristics and Outcome of Therapy-Related Acute Promyelocytic Leukemia After Different Front-line Therapies Sabine Kayser, * Julia Krzykalla, Michelle A. Elliott, Kelly Norsworthy, Patrick Gonzales,
More informationEnasidenib Monotherapy is Effective and Well-Tolerated in Patients with Previously Untreated Mutant-IDH2 Acute Myeloid Leukemia
Enasidenib Monotherapy is Effective and Well-Tolerated in Patients with Previously Untreated Mutant-IDH2 Acute Myeloid Leukemia Pollyea DA 1, Tallman MS 2,3, de Botton S 4,5, DiNardo CD 6, Kantarjian HM
More informationBasics in Geriatric Oncology. Ravindran Kanesvaran Consultant Medical Oncologist and Course Director National Cancer Centre Singapore
Basics in Geriatric Oncology Ravindran Kanesvaran Consultant Medical Oncologist and Course Director National Cancer Centre Singapore How did it start? Ongoing geriatric oncology service at NCCS ( the only
More informationCommunicating Treatment Options to Older Patients: Challenges and Opportunities
Communicating Treatment Options to Older Patients: Challenges and Opportunities Arti Hurria, MD Director, Cancer and Aging Research Program City of Hope National Medical Center Duarte, California, USA
More informationAcute Myeloid Leukemia: A Patient s Perspective
Acute Myeloid Leukemia: A Patient s Perspective Patrick A Hagen, MD, MPH Cardinal Bernardin Cancer Center Loyola University Medical Center Maywood, IL Overview 1. What is AML? 2. Who gets AML? Epidemiology
More informationSurvivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life
1 Survivorship After Allogeneic Stem Cell Transplantation: Monitoring, Management and Quality of Life Stephanie J. Lee, MD, MPH Fred Hutchinson Cancer Research Center April 16, 2016 (40 min) Hematopoietic
More informationLung Cancer in Older Adults.. Appropriate treatment?
Lung Cancer in Older Adults.. Appropriate treatment? Faculty Disclosure X No, nothing to disclose Yes, please specify: Dr Christopher Steer Border Medical Oncology Albury-Wodonga Inaugural Chair Geriatric
More informationBlast transformation in chronic myelomonocytic leukemia: Risk factors, genetic features, survival, and treatment outcome
RESEARCH ARTICLE Blast transformation in chronic myelomonocytic leukemia: Risk factors, genetic features, survival, and treatment outcome AJH Mrinal M. Patnaik, 1 Emnet A. Wassie, 1 Terra L. Lasho, 2 Curtis
More informationRisk-adapted therapy of AML in younger adults. Sergio Amadori Tor Vergata University Hospital Rome
Risk-adapted therapy of AML in younger adults Sergio Amadori Tor Vergata University Hospital Rome Pescara 11/2010 AML: treatment outcome Age CR % ED % DFS % OS %
More informationNational Horizon Scanning Centre. Azacitidine (Vidaza) for myelodysplastic syndrome. September 2007
Azacitidine (Vidaza) for myelodysplastic syndrome September 2007 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to
More informationAllogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms. Policy Specific Section:
Medical Policy Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Type: Medical Necessity and Investigational / Experimental Policy Specific Section:
More informationProblems related to the management of malignant hemopathies in older patients
Problems related to the management of malignant hemopathies in older patients Dr Marie Maerevoet Gent, 25 January 2013 BHS satellite symposium on Elderly Malignant Hemopathies in older patients - 33% of
More informationNeue zielgerichtete Behandlungsoptionen der neu diagnostizierten FLT3-positiven Akuten Myeloischen Leukämie (AML)
Neue zielgerichtete Behandlungsoptionen der neu diagnostizierten FLT3-positiven Akuten Myeloischen Leukämie (AML) Prof. Hartmut Döhner Klinik für Innere Medizin III, Universitätsklinikum Ulm Midostaurin
More informationDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; 2 Sunesis Pharmaceuticals, Inc, South San Francisco
Phase I/II Study of Vosaroxin and Decitabine in Newly Diagnosed Older Patients with Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) Naval Daver 1, Hagop Kantarjian 1, Guillermo
More informationBiological Correlates of Frailty in Older Heart Failure Patients
Biological Correlates of Frailty in Older Heart Failure Patients Dalane W. Kitzman, MD Professor of Internal Medicine: Cardiovascular Medicine and Geriatrics Kermit Glenn Phillips II Chair in Cardiology
More informationSystemic Treatment of Acute Myeloid Leukemia (AML)
Guideline 12-9 REQUIRES UPDATING A Quality Initiative of the Program in Evidence-Based Care (PEBC), Cancer Care Ontario (CCO) Systemic Treatment of Acute Myeloid Leukemia (AML) Members of the Acute Leukemia
More informationStem cell transplantation for patients with AML in Republic of Macedonia: - 15 years of experience -
Stem cell transplantation for patients with AML in Republic of Macedonia: - 15 years of experience - R E S E A R C H A S S O C I A T E P R O F. D - R Z L A T E S T O J A N O S K I Definition Acute myeloid
More informationIntroduction to Hematopoietic Stem Cell Transplantation
Faculty Disclosures Introduction to Hematopoietic Stem Cell Transplantation Nothing to disclose Jeanne McCarthy-Kaiser, PharmD, BCOP Clinical Pharmacist, Autologous Stem Cell Transplant/Long- Term Follow-Up
More informationHow the Treatment of Acute Myeloid Leukemia is Changing in 2019
How the Treatment of Acute Myeloid Leukemia is Changing in 2019 Guido Marcucci, M.D. Director, Gehr Family Center for Leukemia Research Chair, Dept. Hematologic Malignancies Translational Science City
More informationAIH, Marseille 30/09/06
ALLOGENEIC STEM CELL TRANSPLANTATION FOR MYELOID MALIGNANCIES Transplant and Cellular Therapy Unit Institut Paoli Calmettes Inserm U599 Université de la Méditerranée ée Marseille, France AIH, Marseille
More informationDonor Lymphocyte Infusion for Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant
Last Review Status/Date: September 2014 Page: 1 of 8 Malignancies Treated with an Allogeneic Description Donor lymphocyte infusion (DLI), also called donor leukocyte or buffy-coat infusion is a type of
More informationPDF of Trial CTRI Website URL -
Clinical Trial Details (PDF Generation Date :- Wed, 19 Dec 2018 02:45:15 GMT) CTRI Number Last Modified On 25/12/2017 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study
More informationInduction Therapy & Stem Cell Transplantation for Myeloma
Induction Therapy & Stem Cell Transplantation for Myeloma William Bensinger, MD Professor of Medicine, Division of Oncology University of Washington School of Medicine Director, Autologous Stem Cell Transplant
More informationNew drugs and trials. Andreas Hochhaus
New drugs and trials. Andreas Hochhaus Hadera I Oct 2018 Introduction ABL001 is a potent, specific inhibitor of BCR-ABL1 with a distinct allosteric mechanism of action BCR-ABL1 Protein Binds a distinct
More informationThe Role that Geriatricians Can Play in the Care of Older Patients with Cancer Across the Care Continuum
The Role that Geriatricians Can Play in the Care of Older Patients with Cancer Across the Care Continuum Holly M. Holmes, MD, MS Associate Professor and Division Director Geriatric and Palliative Medicine
More informationMinimal residual disease (MRD) in AML; coming of age. Dr. Mehmet Yılmaz Gaziantep University Medical School Sahinbey Education and Research hospital
Minimal residual disease (MRD) in AML; coming of age Dr. Mehmet Yılmaz Gaziantep University Medical School Sahinbey Education and Research hospital 1. The logistics of MRD assessment in AML 2. The clinical
More informationAcute Myeloid Leukemia Progress at last
Acute Myeloid Leukemia Progress at last Bruno C. Medeiros, MD September 9, 217 Introduction Mechanisms of leukemogenesis Emerging therapies in AML Previously untreated AML Relapsed and refractory patients
More informationPreoperative Assessment Guidelines in the Elderly
Preoperative Assessment Guidelines in the Elderly How Are They Helping? Mark R. Katlic, M.D., M.M.M. Chairman, Department of Surgery Director, Center for Geriatric Surgery Sinai Hospital Baltimore, Maryland
More informationNational Institute for Health and Care Excellence. Single Technology Appraisal (STA)
Single Technology Appraisal (STA) Gemtuzumab ozogamacin for untreated de novo acute myeloid leukaemia Response to consultee and commentator comments re-scope Please note: Comments received in the course
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 3,500 108,000 1.7 M Open access books available International authors and editors Downloads Our
More informationDr Kavita Raj Consultant Haematologist Guys and St Thomas Hospital
Dr Kavita Raj Consultant Haematologist Guys and St Thomas Hospital IPSS scoring system Blood counts Bone marrow blast percentage Cytogenetics Age as a modulator of median survival IPSS Group Median Survival
More informationIndication for unrelated allo-sct in 1st CR AML
Indication for unrelated allo-sct in 1st CR AML It is time to say! Decision of allo-sct: factors to be considered Cytogenetic risk status Molecular genetics FLT3; NPM1, CEBPA. Response to induction Refractoriness
More information