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Lay Summary: People who have advanced myelodysplastic syndromes (MDS) may live longer if they get a bone marrow transplant (BMT) instead of other therapies. However, only 15% of people with MDS actually get BMT. Experts say community physicians and transplant physicians should team up with insurance companies and patient advocacy groups to 1) spread this news about lifesaving advances in BMT, 2) ensure that everyone can afford health care, 3) provide emotional support for patients and families, 4) help patients and families get transportation and housing if they need to travel for transplant, and 5) improve care for people of under-represented racial and ethnic backgrounds., (© 2021 American Cancer Society.)

Background: The development of novel therapies for the myelodysplastic syndromes (MDS) is hampered by inadequate trial recruitment. Factors contributing to low trial accrual are incompletely understood., Methods: This study analyzed a pooled patient database from institutions of the US MDS Clinical Research Consortium to compare the characteristics of participants in interventional trials with those of patients who did not enroll in a trial., Results: Data were identified for 1919 patients with MDS, and 449 of these patients (23%) participated in an interventional clinical trial. The median age of all patients was 68 years, and 64% were male. Patients who participated in trials were significantly younger than nonparticipants (P = .014), and men were more likely to participate in a trial (71% of trial participants were male, whereas 61% of nonparticipants were; P < .001). Race and ethnicity were not associated with trial enrollment. Patients in more affluent ZIP codes had a higher participation rate (P < .001). Patients with intermediate- and high-risk disease according to the revised International Prognostic Scoring System were overrepresented (P = .004), and trial participants less frequently had treatment-related disease (P < .001). In multivariable analyses, participation in a clinical trial was associated with a reduced hazard of death (P = .004). Even at large referral centers, only a minority of patients with MDS enrolled in interventional trials., Conclusions: Restrictive trial eligibility criteria that exclude patients with MDS on account of age, comorbidities, or a history of another cancer are limit enrollment of MDS patients to clinical trials. Gaining insight into the barriers to trial accrual may help investigators and study sponsors to design trials that will accrue more rapidly and augment treatment options for patients with MDS., (© 2020 American Cancer Society.)

Background: Older adults with acute myeloid leukemia (AML) are often assumed to have poor outcomes after admission to the intensive care unit (ICU). However, little is known about ICU utilization and post-ICU outcomes in this population., Methods: The authors conducted a retrospective analysis for 330 patients who were 60 years old or older and were diagnosed with AML between 2005 and 2013 at 2 hospitals in Boston.They used descriptive statistics to examine the proportion of patients admitted to the ICU as well as their mortality and functional recovery. They used logistic regression to identify risk factors for in-hospital mortality., Results: Ninety-six patients (29%) were admitted to the ICU, primarily because of respiratory failure (39%), septic shock (28%), and neurological compromise (9%). The proportions of patients who survived to hospital discharge, 90 days, and 1 year were 47% (45 of 96), 35% (34 of 96), and 30% (29 of 96), respectively. At 90 days, 76% of the patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and 86% were in complete remission (CR) and/or continued to receive AML-directed therapy. In a multivariate analysis, a poorer baseline ECOG PS score (odds ratio, 2.76; P = .013) and the need for 2 or more life-sustaining therapies (ie, vasopressors, invasive ventilation, and/or renal replacement therapy; odds ratio, 12.4; P < .001) were associated with increased odds of in-hospital mortality., Conclusions: Although almost one-third of older patients with AML are admitted to an ICU, nearly half survive to hospital discharge with good functional outcomes. The baseline performance status and the need for 2 or more life-sustaining therapies predict hospital mortality. These data support the judicious use of ICU resources for older patients with AML., (© 2019 American Cancer Society.)

Despite few effective therapies, only a small percentage of patients diagnosed with myelodysplastic syndromes (MDS) in the United States are enrolled in prospective, interventional clinical trials. MDS-specific barriers to trial accrual include a high frequency of elderly patients with comorbid conditions, atypical disease features and uncertainty regarding the diagnosis (because other nonclonal processes also can cause dysplasia and cytopenias), a history of another nonmyeloid neoplasm resulting in therapy-related MDS, rapid disease recurrence after allogeneic stem cell transplantation, and an arbitrary division between MDS and acute myeloid leukemia. In addition, barriers to accrual that are common to other oncology populations, such as difficulty traveling to clinical trial enrollment sites and narrow trial eligibility criteria, also prevent patients with MDS from enrolling in studies. Collectively these barriers must be assessed systematically, and creative solutions are needed to improve outcomes for this needy patient population., (© 2018 American Cancer Society.)

Hypomethylating agents (HMAs) have changed the landscape of the management of patients with higher-risk myelodysplastic syndromes (HR-MDS). HMAs have improved hematopoiesis and quality of life and, in the case of azacitidine, prolonged survival in a large randomized trial. However, multiple real-life and registry analyses have demonstrated minimal survival gains at the population level after the approval of HMAs. Furthermore, the 24-month median survival observed with azacitidine in the landmark AZA-001 trial has not been replicated in population-based studies or in other clinical trials using azacitidine monotherapy arms. Herein, we critically review the accumulating data suggesting that the actual survival impact of HMAs, especially azacitidine, in patients with HR-MDS is significantly lower than what was observed in the AZA-001 trial and what often is quoted to patients, and discuss the potential explanations for this discrepancy. We also present the rationale for why front-line clinical trial enrollment should be always considered and discussed with every newly diagnosed patient with HR-MDS rather than defaulting to the routine use of HMAs. Finally, we review the challenges to wider-scale enrollment in front-line HR-MDS clinical trials and suggest solutions to accelerate this process with the ultimate goal of achieving a real and substantial change in the natural history of this aggressive malignancy. Cancer 2017;123:3662-3672. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Outcomes among older patients with acute lymphoblastic leukemia remain poor. This study sought to determine the efficacy of an intensified, multi-agent approach derived from a Dana-Farber consortium trial in younger adults for patients older than 50 years (trial identifier NCT00973752)., Methods: The primary endpoint was overall survival (OS) at 1 year. Patients received induction chemotherapy with vincristine, prednisone, doxorubicin, and pegylated asparaginase. Imatinib was incorporated for Philadelphia chromosome-positive disease. After induction, the first consolidation incorporated clofarabine. Patients in remission could proceed to allogeneic hematopoietic cell transplantation (HCT) after induction and consolidation I. Those not receiving HCT went on to receive central nervous system, consolidation II, and continuation phases of treatment., Results: Thirty patients were enrolled: 19 achieved a complete remission (CR) after induction and 1 achieved CR after consolidation I for a CR rate of 67%. Sixteen patients underwent HCT. The proportion surviving at 1 year was 63%, and this met the primary endpoint. The 2-year OS rate was 52% (n = 30), and the 2-year disease-free survival rate was 52% for patients achieving CR (n = 20). There was no survival advantage among those undergoing HCT. Therapy-related hyperbilirubinemia prompted adjustments and limitations to asparaginase dosing., Conclusions: Intensified chemotherapy can result in improved outcomes in comparison with historical data. Additional studies of similarly intensive regimens are warranted in this population. Cancer 2016;122:2379-2388. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Contract research organizations (CROs) represent a multibillion dollar industry that is firmly embedded in the contemporary clinical trial process. Over the past 30 years, and especially within the last decade, the reach of CROs has extended to service all phases of drug trials in an increasingly global research environment. The presence of CROs is particularly noticeable in medical oncology because of the large number of investigational compounds developed to treat cancer that are currently undergoing testing in human subjects. Although limited data are available with which to objectively define the effects that CROs have had on the clinical trial process, with the expansion of these organizations, several reports have called into question whether ethical and professional standards in research conduct are at times secondary to economic considerations. CROs can add considerable value to the clinical trial process, but difficulty communicating with CRO representatives and time spent answering trivial data queries generated by CROs are current obstacles for study site personnel interacting with CROs. Further study of the effect of the CRO industry on the clinical trial process is needed to ensure efficient data collection and patient safety while collaboratively developing novel therapies in an expedited fashion. Cancer 2016;122:1476-82. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: As the population ages, the prevalence of myelodysplastic syndromes (MDS) will increase, and many patients with MDS will require end-of-life (EOL) care. Little is known about the intensity of EOL care received by patients with these malignancies., Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database and standard EOL quality measures, we assessed the prevalence and predictors of intensive care unit (ICU) admission in the last 30 days of life, chemotherapy in the last 14 days of life, and hospice enrollment among MDS patients who were 65 years old or older and died between 2006 and 2011., Results: Of 6,955 patients, 28% were admitted to the ICU and 7% received chemotherapy near the EOL, while 49% enrolled in hospice. In multivariable models, patients dependent on red blood cell or platelet transfusions at the EOL were less likely to enroll in hospice (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.61-0.78). Nonwhite patients were less likely to enroll in hospice (OR, 0.77; 95% CI, 0.67-0.89) and more likely to be admitted to the ICU near the EOL (OR, 1.19; 95% CI, 1.03-1.38). Finally, the prevalence of hospice enrollment increased in later years (P < .001)., Conclusions: The intensity of EOL care for patients with MDS varies but is potentially suboptimal with respect to the traditional measure of hospice use. The lower odds of enrollment for transfusion-dependent patients suggest that the current hospice model, which largely disallows transfusions, may not be meeting the palliative needs of this population., (© 2016 American Cancer Society.)

Background: Health care utilization in older adults (age ≥60 years) with acute myeloid leukemia (AML) has not been well studied., Methods: We conducted a retrospective analysis of 330 consecutive older patients who were diagnosed with AML between May 1, 2005 and December 23, 2011, at 2 hospitals in Boston to examine their health care utilization and end-of-life care. Using multivariable logistic and linear regression models adjusting for covariates, we also compared health care utilization between patients who received intensive induction chemotherapy (n = 197; cytarabine/ anthracycline combination) versus nonintensive chemotherapy (n = 133; single-agent therapy)., Results: The median number of hospitalizations for the entire cohort was 4.2 (range, 1-18 hospitalizations). Patients who died spent a mean of 28.3% of their life after diagnosis in the hospital and 13.8% of their life attending outpatient clinic appointments. Although the majority of patients (87.9%) died during the 2-year follow-up period, a minority received palliative care (16.2%) or hospice (23.1%) services. Within 30 days of death, 84.5% of patients were hospitalized, and 61% died in the hospital. Among the patients who died, those who received intensive induction therapy (vs nonintensive therapy) spent 30% more of their life after diagnosis in the hospital (P < .0001) and were less likely to receive hospice services (odds ratio, 0.45; P = .05)., Conclusions: The current findings highlight the intensity of health care utilization among older patients with AML, regardless of treatment modality. Despite the poor prognosis, palliative care and hospice services are rarely used. Future work should study novel health care delivery models to optimize care throughout the course of illness and at the end of life., (© 2015 American Cancer Society.)

Background: The hypomethylating agents (HMAs) azacitidine and decitabine are most commonly used to treat patients with higher-risk myelodysplastic syndromes (MDS). To the authors' knowledge, the prognosis of patients with low-risk and intermediate-1-risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure has not been explored comprehensively., Methods: The clinical characteristics and treatment outcome of 438 patients with low-risk and intermediate-1-risk MDS who were treated with HMAs were retrospectively analyzed., Results: Using the International Working Group response criteria, the overall objective response to HMA was 35% with a median of 6 cycles of HMA administered, and the median response duration was 7 months. Only 7% of patients had disease that transformed into acute myeloid leukemia while receiving therapy. Of the 290 patients who were evaluable at the time of HMA failure, 77% remained in the lower-risk disease categories. On multivariate analysis, baseline neutropenia, intermediate-risk and poor-risk baseline karyotype, and lack of response to HMA were found to be independently associated with a higher risk of disease progression. With a median follow-up of 16 months, the median transformation-free survival and overall survival (OS) after HMA failure were 15 months and 17 months, respectively. On multivariate analysis, only The University of Texas MD Anderson Global Scoring System was found to be independently predictive of outcome, with patients with higher-risk categories having poor transformation-free survival (hazards ratio [HR], 1.5; P = .003) and OS (HR, 1.8; P = .002). The administration of salvage therapy was independently associated with better OS only (HR, 0.8; P = .01)., Conclusions: Outcomes of patients with lower-risk MDS after HMA failure are poor and the treatment of these patients remains an unmet medical need. OS is a reasonable primary endpoint for clinical studies targeting this population., (© 2014 American Cancer Society.)

Background: Previous studies have suggested that many patients with myelodysplastic syndromes (MDS) have an incomplete understanding of their disease, which may influence adherence to prescribed regimens and outcomes., Methods: To better understand physician and patient perceptions about MDS and MDS therapy, the authors conducted 2 surveys in February 2012: 1 for patients with MDS and 1 for health care professionals (HCPs) who cared for patients with MDS. Patient and HCP surveys consisted of 57 and 49 questions, respectively, assessing understanding of MDS, perceptions of specific treatments, barriers to treatment adherence, and treatment experience., Results: In total, 477 complete patient responses and 120 complete HCP responses were received. Among patient responders, 63% were aged ≥60 years, and 42% had received at least 1 disease-modifying therapy. Of the 61 physician responders, 57% practiced in an academic setting, and 43% practiced in the community; 71% of the 59 nonphysician HCPs worked in the community setting. Only 10% of patients agreed that MDS represented "cancer" compared with 59% of physicians and 46% of nonphysician HCPs (P < .001). Only 29% of patients reported that MDS was ever "curable" compared with 52% of physicians (P < .001). Physicians viewed the potential benefits of active therapy as greater than patients, but patients perceived the actual treatment experience more positively than physicians and differed from physicians in perceived reasons for stopping therapy., Conclusions: Physicians, nonphysician HCPs, and patients with MDS have disparate views of MDS characteristics and the value and limitations of treatments for MDS. Improved communication and education may increase understanding and achieve better treatment adherence and patient outcomes., (© 2014 American Cancer Society.)

Aims: Central sleep apnoea (CSA) and increased serum erythropoietin (EPO) concentration have each been associated with adverse prognosis in heart failure (HF) patients. The aim of this study was to examine the relationship between nocturnal hypoxaemia due to CSA and the serum EPO concentration in patients with HF., Methods and Results: Heart failure subjects (n = 33) and healthy controls (n = 18) underwent polysomnography (PSG) for diagnosis of CSA and identification and quantification of hypoxaemia. Blood collection for measurement of EPO was performed immediately post-PSG. For the analysis, HF subjects were dichotomized into subgroups defined by the presence or absence of CSA and by HF severity. Multivariate analyses were performed to evaluate the relationships of hypoxaemia and advanced HF to EPO concentration. Mean EPO concentration was 62% higher for HF subjects with CSA than for healthy controls (P = 0.004). The magnitude of nocturnal hypoxaemia was significantly and positively related to EPO concentration (r = 0.45, P = 0.02). Advanced HF was also significantly and positively related to EPO concentration (r = 0.43, P = 0.02). On multivariate analysis, the presence of combined nocturnal hypoxaemia and advanced HF yielded greater correlation to EPO concentration than either factor alone (r = 0.57, P = 0.04 and P = 0.05, respectively). Linear regression demonstrated that the combination of New York Heart Association Class and CSA was strongly associated with EPO concentration (P < 0.0001)., Conclusion: In non-anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.