Incidence Of Acute Myeloid Leukemia Research Articles

Allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia

The incidence of acute myeloid leukemia (AML) significantly increases with age. Most AML patients are elderly and rarely receive curative treatment. Even those who eventually achieve complete remission have a grim prognosis due to the high risk of relapse. In elderly patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases the probability of prolonged survival compared to standard treatment. The decision as to whether to refer a patient for transplantation must be preceded by a careful risk assessment based on the patient’s remission status, comorbidities, and type of available donor. Although allo-HSCTs are routinely performed in the seventh decade of life, they are not common in those aged over 70. In recent years, the results of allo-HSCT in the elderly have improved, mainly thanks to refined conditioning regimen techniques and better supportive care. It can be anticipated that with growing data on allogeneic transplants in older AML patients, the proportion of this population among transplant recipients will continue to rise.

Incidence of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Patients With Inflammatory Bowel Disease and the Impact of Thiopurines on Their Risk.

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are rare myeloid clonal disorders that commonly affect the elderly population and have poor prognosis. There are limited data on the risk of AML/MDS among patients with inflammatory bowel disease (IBD), especially on the impact of thiopurines (TPs). We conducted a retrospective cohort study among patients with IBD from Veteran Affairs data set. The exposure of interest was TP exposure: (i) never exposed to TPs, (ii) past TP use (discontinued >6 months ago), (iii) current TP use with a cumulative exposure of <2 years, and (iv) current TP use with a cumulative exposure of ≥2 years. The outcome of interest was a composite outcome of incident diagnosis of AML and/or MDS. Cox regression was used to estimate the adjusted and unadjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for AML/MDS risk associated with TP use defined as a time-varying exposure. Among 56,314 study patients, 107 developed AML/MDS. The overall incidence of AML/MDS in the IBD population was 18.7 per 100,000 patient-years. The incidences among those never exposed to TPs, past users of TPs, current users of TPs with a cumulative exposure of <2 years, and current users of TPs with a cumulative exposure of ≥2 years were 17.0, 17.7, 30.4, and 30.3 per 100,000 patient-years, respectively. In multivariable Cox regression analysis, compared with never exposed to TPs, current use of TPs was associated with increased risk (adjusted HR 3.05; 95% CI 1.54-6.06, P = 0.0014 for current use of TPs with a cumulative exposure of <2 years and adjusted HR 2.32; 95% CI 1.22-4.41, P = 0.0101 for current use of TPs with a cumulative exposure of ≥2 years), whereas past TP exposure was not. Among patients with IBD, current TP use was associated with an increased risk of AML/MDS, which reverts to baseline after discontinuation of TP use.

P53 Downregulation-Based Strategy to Protect Genomic Integrity from Radiation Therapy

Background: Activation of p53 is one of major pathways by which DNA damaging agents (DDA) such as radiation and chemotherapy cause toxicity in normal tissues and it induces a cascade of events that eventually leads to cell senescence or cell death. We have reported that a brief pretreatment with low dose arsenic (LDA), by temporarily and reversibly downregulating p53 at the time of treatment with DDA, reduces the normal tissue toxicity without compromising tumor response to treatment. This protective effect is selective to normal tissues, as it requires functional p53. Though not every cancer cell has detectable p53 mutations, essentially every cancer cell has dysfunctional p53. Therefore most cancer cells will not be protected by this strategy. Genomic instability and inability to repair DNA damage from DDA in the hematopoietic stem cells have been attributed to the development of therapy-induced myelodysplastic syndrome (tMDS) and acute myeloid leukemia (AML). We have also been studying the effect of LDA on the genome in the setting of cancer therapy. We have reported that LDA pretreatment significantly reduces radiation-induced DNA double strand breaks (DSBs) and apoptosis in normal cells both in-vitro and in-vivo. Persistent DNA damage such as DSBs can trigger genomic instability and can be prevented by proper DNA repair. Our previous work using comet assay to quantify DNA damage after radiation has indicated that DNA repair capacity is enhanced by LDA pretreatment. A role for LDA in maintaining genomic integrity has been implicated in our in-vitro studies, where we found that LDA protected telomeres from enhanced erosion by DDA in Concanavalin A-activated normal human lymphocytes, and that LDA reduced spontaneous and radiation-induced mutations in mouse embryonic stem cells. Yet, whether this p53 downregulation-based strategy helps genome maintenance during cancer treatment using DDA has not been investigated in-vivo. CBA/Ca mice have 15-25% incidence of AML after 3 Gy of total body ionizing radiation (IR). About 95% of mice that develop radiation-induced AML (rAML) have a deletion on chromosome 2 encompassing the PU.1 gene. Since PU.1 deletion is a critical contributor to and a useful surrogate marker for leukemogenesis in the murine rAML model, we tested a hypothesis whether pretreatment with LDA before IR helps maintain genomic integrity by evaluating bone marrow cells for PU.1 gene deletion. Method: One hundred twenty mice were randomized into four groups: PBS+sham IR (control), LDA+sham IR, PBS+IR and LDA+IR. Prior to sham or 3 Gy of IR, CBA/Ca mice were injected with either PBS or LDA intraperitoneally at the dose of 0.4mg/kg for 3 days. At 7, 30 and 180 days after radiation, bone marrow cells were collected from femurs and fixed with Carnoy's Fixative. To assess the effect of LDA on PU.1 gene deletion, fluorescence in-situ hybridization (FISH) assay was performed. An ATTO550 labeled PU.1 probe was designed and used to detect deletions that occur in 2qE1 and involve the PU.1 gene locus, as well as two 6-FAM labeled probes for centromere and telomere respectively. Four to five hundred cells were analyzed for each mouse. Statistical significance was determined from a two-way analysis of variance in log units using SAS Version 9.4. Result: We successfully established the FISH assay that can specifically detect the PU.1 gene not only in metaphase cells but also in interphase cells. As shown in the figure, mice in the LDA+IR group have significantly fewer bone marrow cells exhibiting PU.1 gene deletion compared with PBS+IR group at all three time points examined (Day 7: 2±1.2% vs 3.7±2.6%, P=0.047; Day 30: 1.9±1.1% vs 3.2±1.9%, P=0.040; Day 180: 2.8±1.0% vs 5.6±3.5%, P=0.014). LDA treatment alone has a negligible effect on PU.1 loss as compared to the control group. Conclusion: Our result suggests that LDA pretreatment protects genomic integrity following IR treatment in-vivo. As the development of rAML is a multi-step process, the impact of LDA pretreatment on the actual incidence of secondary malignancy needs further validation in animal models. The genome-protective effect of LDA that we have revealed supports its potential use as a strategy to reduce the development of radiation-induced secondary malignances such as MDS and AML. Disclosures Ha: Protectum Oncology: Current Employment, Current equity holder in private company.

Prospective Population-Based Analysis of Characteristics and Therapy Options in AML: The Case of Catalonia (PERIS Project)

Introduction:Acute myeloid leukemia (AML) real-world incidence has been investigated in a limited number of European countries such as Sweden, Denmark and a few others. These prospective population-based analyses give a more precise idea of AML as a health problem than registry data from cooperative groups or other sources, that usually include selected cases as part of research studies and/or therapy trials. In October 2016, the Autonomous Government of Catalonia funded a project (PERIS SLT002/16/00433) to prospectively collect all AML cases from our territory. Objective:To investigate the incidence, characteristics and treatment decisions in all consecutive AML patients diagnosed in Catalonia between January 2017 and December 2019. Methods:Inclusion criteria were diagnosis of AML according the WHO 2016 criteria, both primary and secondary (APL excluded) with an age &amp;gt;18 years. The project was disseminated to all hospitals from Catalonia regardless of their size, having at least one hematologist. A specific informatics tool was implemented for remote reporting of the cases. All data were anonymized. In parallel, a circuit for centralized bio banking of patients' samples was designed. The database included the main clinical, laboratory data as well as the initial therapeutic approach. Cases included in our CETLAM group cooperative studies were automatically linked to the trial database for collecting detailed information. Statistical analyses were performed with R packages. Results:Assuming an incidence of AML of 4 cases per 100,000 inhabitants (based on previous reported data from others), we expected 912 cases during three years in the 7,6 million population of Catalonia. Our prospective registry included 750 consecutive AML patients, 82% of the expected cases. The remaining 18% could be explained by the exclusion of APL, age below 18 years, or underreporting. Seventy percent of patients (n=527) were diagnosed and treated in the 5 large University Hospitals from Barcelona and the two adjacent cities (Badalona and Hospitalet). Table 1 shows the main characteristics of the patients. Among the 390 patients up to 70 years, 272 (70%) were enrolled in the CETLAM AML-12 protocol that included intensive chemotherapy (ICT) and risk adapted hematopoietic cell transplantation (HCT). Forty-one additional patients (11%) in this age group received other ICT in different clinical trials. A remaining 73 patients (20%) were treated with other intensive or non-intensive approaches outside trials. In the group of 360 patients older than 70 years only a 33% (n= 119) were treated under the risk-adapted CETLAM AML-16 protocol for elderly AML patients. This trial included ICT as in the CETLAM-12 in case of favorable genetic features; this was received by 13 of the 119 patients (11%) enrolled. The remaining patients of CETLAM-16 were treated with low-intensity chemotherapy (oral fludarabine, subcutaneous (SC) cytarabine and G-CSF or azacytidine) and 97 additional elderly patients were included in other clinical trials mostly with targeted and hypomethylating agents (27%). Other active therapies outside trials (usually low-intensity) were administered in 50 additional patients (14%) whereas the remaining 94 patients (26%) only received supportive measures (transfusions, hydroxyurea, antibiotics, palliation, or no treatment), because of one or more of the following: advanced age, poor AML features or severe clinical condition. Overall survival (OS) of the whole series at 2 years was 31±2% (CI: 27-35). Patients younger than 70 years had a 2-year OS of 47±3% (CI: 41-53) compared to 11±3% (CI: 7-17) for those above 70 years (p&amp;lt;0.001) (Image 1). Conclusions:This prospective study is highly representative of the diagnosis and treatment of AML in Catalonia. The median age at diagnosis was 70 years. Of note, 81% of patients up to 70 years were enrolled in ICT trials. The proportion of patients in trials in the elderly group was lower although still remarkable (60%). In this advanced age group, a 26% of patients were treated with supportive measures only. Despite the high inclusion rate in clinical trials, only one third of newly diagnosed AML patients have the probability to survive at 2 years, with a dismal outcome in those above 70 years. Therefore, the investigation of novel and more effective treatments remains mandatory. This series will be detailed and updated during the meeting. Disclosures Salamero: Pfizer:Consultancy;Jazz Pharmaceuticals:Consultancy, Honoraria;Daichii Sankyo:Honoraria;Novartis:Consultancy, Honoraria;Celgene:Consultancy, Honoraria.Olivera:BAYER:Consultancy;Pfizer:Consultancy, Speakers Bureau;Daiichi Sankyo:Consultancy, Speakers Bureau;Boehringer Ingelheim:Consultancy, Speakers Bureau.Sureda Balari:Celgene:Consultancy, Honoraria;Merck Sharpe and Dohme:Consultancy, Honoraria, Speakers Bureau;Sanofi:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;Gilead/Kite:Consultancy, Honoraria;Janssen:Consultancy, Honoraria;Incyte:Consultancy;Roche:Honoraria;BMS:Speakers Bureau;Celgene/Bristol-Myers Squibb:Consultancy, Honoraria;Takeda:Consultancy, Honoraria, Speakers Bureau.Ribera:Pfizer, Amgen:Research Funding;Pfizer, Amgen, Ariad, Novartis:Consultancy, Speakers Bureau.Sierra:Jazz Pharmaceuticals:Research Funding;Pfizer:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Daiichi Sankyo:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead-Kite:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Annual Healthcare Resource Utilization and Costs in US Patients Diagnosed with Relapsed Acute Myeloid Leukemia

Introduction: Acute myeloid leukemia (AML) is a malignant form of bone marrow cancer commonly diagnosed in older adults. The age-adjusted incidence of AML in the USA is 4.3 per 100,000, with a median age of 68 years at diagnosis. Once diagnosed, treatment options include intensive chemotherapy to induce remission followed by post-remission therapies, including stem cell transplantation, repeated rounds of intensive chemotherapy to achieve durable disease control, or supportive care. Prognosis following relapse is poor with a median survival of 8-10 months. While previous studies have shown that much of this time following relapse is spent in an inpatient or outpatient setting, few studies have looked at the frequency and costs of this healthcare utilization. This study examined annual healthcare resource utilization and associated costs incurred in patients diagnosed with relapsed AML. Methods: A retrospective analysis was conducted in the Premier Healthcare Database, a nationally representative, all-payer hospital administrative database containing more than 1 billion inpatient and hospital-based outpatient encounters. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for AML in relapse, the study identified adult patients during the period from January 1, 2016 to March 31, 2019. The date of the first encounter with a relapse diagnosis served as the index date. Patients were followed from index date to inpatient death, one year post-relapse, or end of study period (September 30, 2019). Unadjusted descriptive analyses were performed to describe patient demographics, hospital characteristics, and comorbid conditions, as well as outcomes of interest, including outpatient treatment days, inpatient and intensive care unit (ICU) admissions, and associated costs. Results: A total of 2,290 patients were identified for inclusion in the study. Mean age was 61.2 years (median 65.0 years) and 46.9% were female. Healthcare coverage was Medicare (51.2%), commercial insurance (29.1%), Medicaid (13.8%), or other (5.9%). Mean Charlson Comorbidity Index was 4.02 (SD 2.66) and common comorbidities were diabetes (31.0%), congestive heart failure (19.5%), and chronic obstructive pulmonary disease (19.0%). Patients' length of follow-up varied: &amp;lt; 90 days (49.4%), ≥ 180 days (32.8%), and ≥ 360 days (16.8%). During the 1-year follow-up period, patients were seen in the outpatient hospital treatment setting for a median of 7.0 (IQR 2-19) days. In addition to outpatient treatment, patients incurred a total of 1,798 inpatient hospitalizations (median 2.0 per patient, IQR 1-3), with a median length of stay (LOS) of 10.0 (IQR 6-19) days. Among hospitalized patients, 554 (30.8%) included an ICU admission with a median LOS of 3.0 (IQR 1-5) days per admission. Median cost per day for outpatient treatment was $1,039 (IQR $487-2,305) and patients incurred a median cost of $6,569 (IQR $1,872-23,542) in this setting. For hospitalizations, median cost of an inpatient stay was $21,592 (IQR $9,852-45,000). Cost of an ICU admission during a hospital stay was $13,348 (IQR $6,115-28,266). Hospital treatment costs incurred by this cohort of patients in the year following relapse totaled $169 million, of which 82% ($139 million) was attributable to the inpatient setting. Conclusions: After a relapse of AML, patients are commonly admitted to the hospital, oftentimes to the ICU, and incur substantial costs associated with treatment. These results suggest that cost savings could be realized with therapies that would forestall relapse and improve survival in patients with AML. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Knoth:Bristol Myers Squibb: Current Employment. Huggar:FibroGen: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company. Copher:Bristol Myers Squibb: Current Employment. Cao:Bristol Myers Squibb: Research Funding; Precision Xtract: Current Employment. Lipkin:Premier Inc.: Current Employment; Bristol Myers Squibb: Other: Premier Inc. received funding from BMS to conduct this research. Leblanc:UpToDate: Patents &amp; Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding.

Epidemiology of Acute Myeloid Leukaemia in New Zealand: A National Cancer Registry Analysis

Background: Acute myeloid leukaemia (AML) is a blood cancer characterised by the expansion of a malignant myeloid progenitor. The estimated age-standardised incidence rate in many western countries has remained static over the last 2 decades at 3-4 per 100,000, whilst long-term survival has improved, especially for the younger individuals. However, disparities remain for the older individuals, people of ethnic minority background, and those who are more socio-economically deprived. Previous evaluation of population data from New Zealand has shown a similar pattern, but a more recent analysis has not been done. Here we present the incidence and long-term survival of patients with AML in New Zealand (NZ), using the New Zealand Cancer Registry (NZCR). Method: The NZCR was established in 1948 and it became mandatory by law to report all new cases of malignancy by 1994. We extracted all AML cases from the registry between 1 January 1997 and 31 December 2016. Cases with an ICD-10-CM code for acute myeloid leukaemia and its subtypes including acute promyelocytic leukaemia (e.g. C92.0) were included. Individuals residing overseas or without an address were excluded, and individuals with a diagnosis of acute promyelocytic leukaemia (APML) were analyzed separately. The socio-economic status of the individual was estimated based on their domicile area using the New Zealand 2013 Index of Deprivation (NZDep2013) which is a geographically based composite measure of deprivation. Overall survival was calculated from the date of diagnosis to the date of death or last follow-up (31 December 2016). Multivariable Cox-proportional hazard models were used to evaluate potential associations with survival time in NZ AML cases. Results: During this 20-year period, 154 cases of APML and 2876 cases of AML (excluding APML) were reported to the registry on individuals residing in New Zealand. Of the AML cases, 53% were male and the median age at the time of diagnosis was 67 (IQR 52-77), with a small positive correlation between year of diagnosis and age at diagnosis (Spearman's rho=0.05, p=0.009). The majority of cases (77%) were of European descent, 12% were New Zealand Maori, and 6% were Pacific Islanders. Individuals of European descent were significantly older at diagnosis compared to other ethnicities (median of 70 vs 51 for Maori, 56 for Pacific Islanders, and 58 for all other ethnicities, p&amp;lt;0.001). AML appeared to disproportionally affect those more socio-economically deprived, with 23% of cases reported in the most deprived 20% of the population, compared with only 16% of the cases in the least deprived 20%. The annual crude incidence remained stable during this period at an average of 3.42 per 100,000 (ranging from 2.57 to 4.29, figure 1), and was significantly higher in the older adults (figure 2). Age-standardised rates were lower (figure 1), with an average of 2.6 (range 1.9 to 3.4) cases per 100,000, and a small but significant average annual decrease over the study period. The estimated 1, 2, and 5-year survival for the entire cohort was 38%, 27%, and 22%, respectively. Age at diagnosis was a significant predictor of inferior survival, with a hazard ratio (HR) for all-cause mortality of 2.06, 3.95, 6.39 and 10.84 for the 50-59, 60-69, 70-79 and &amp;gt;80 age groups, respectively, compared to those aged &amp;lt;50. Shorter overall survival was also noted in individuals in the more socio-economically deprived 50% of the population (HR 1.13, 95% CI 1.03-1.23). Conclusion The incidence of AML in New Zealand has remained static in the last 2 decades, consistent with data from other western countries. Lower age-standardised rates and the small decrease in these observed over the study period are likely to reflect the increasingly and comparatively older population in NZ. Maori and Pacific Islanders appeared to present at a younger age than individuals of European descent. Age at diagnosis and socio-economic deprivation were shown to be an adverse prognostic factor for overall survival. Further in-depth analysis is required to determine the cause of these observations at a population level. Disclosures Chan: AbbVie:Membership on an entity's Board of Directors or advisory committees;Janssen:Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau;Celgene:Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company);Amgen:Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company);Roche:Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company).

Incidence and Outcome of Acute Myeloid Leukemia in Peru: An 11-Year Single Center Experience

Background: Acute myeloid leukemia (AML) is a highly heterogeneous disease with new cases commonly diagnosed in the elderly population. Despite advances in AML therapy, disease outcomes remain poor. Between 2010 and 2016, the reported 5-year overall survival in the U.S. was 28.7% (Source: NCI SEER 13 statistics). National based registries are vital to monitor the incidence, outcome and survivorship of AML patients. Therefore, we aim to explore the incidence and outcome of AML patients managed at the National Cancer Institute in Peru over the past decade. Methods: We conducted a retrospective analysis of all newly diagnosed AML patients seen at the National Cancer Institute (INEN) in Lima-Peru between January 2008 to December 2018. The INEN is the major governmental leukemia center providing care for about 60% of newly diagnosed AML patients in Peru. Patient eligibility screening was performed using the Flow Cytometry Core Lab Registry. We excluded patients with acute promyelocytic leukemia. Demographic and clinical characteristics were obtained from medical records. Place of birth and death records were confirmed using the Peruvian National Registry of Identification and Civil Status (RENIEC). Survival analysis was performed using Kaplan Meier and Log-rank tests. The cumulative 11-year AML incidence rate was calculated and plotted using a choropleth map of Peru. Results: A total of 1,499 newly diagnosed AML cases were identified and had sufficient data for analysis. Median age at diagnosis was 44 years (range: 0-92) with a female:male ratio of 0.9:1. Clinical characteristics and outcome are presented in Table 1. Twenty-two percent (n=324) of patients were older than 65 years-old at the time of diagnosis. Most patients (n=926, 62%) came from the coastal region of Peru, followed by the mountains (30%) and the rainforest (8%). The cumulative 11-year incidence rate according to geographical location is shown in Figure 1. Overall, the Peruvian hospital-based cumulative incidence rate was 4.79 AML cases per 100,000 habitants, with the highest incidence rate observed in Piura (a coastal city in Northern Peru) with 38 AML cases per 100,000 habitants. At a median follow up of 68 months, the global 5-year overall survival (OS) rate of AML cases seen in Peru was 16%. Worse survival rates were found in patients aged 66 years and older (5-year OS 3%, median survival time [MST] 2 months, p&amp;lt;0.001), followed by patients aged 46 to 65 years (5-year OS 9%, MST 2 months, p&amp;lt;0.001) (Figure 2). Better survival rates were observed in children and adolescents (5-year OS 43%, MST 18 months, p&amp;lt;0.001) and in patients coming from the rainforest of Peru (5-year OS 26%, MST 9 months, p&amp;lt;0.001) (Figure 2). No differences on survival were found when comparing by gender and year of diagnosis (Table 1). Conclusions: This is the first study describing the incidence and outcome of AML patients in Peru. In this large contemporary cohort, we found a cumulative 11-year incidence rate of 4.79 AML cases per 100,000 habitants, with an alarming high incidence of AML cases observed in the city of Piura which needs further epidemiological evaluation. Despite improvements in supportive care in the contemporary era, our inpatient mortality for adult patients with AML remains high particularly among older patients. Further analyses are warranted to examine predictors of AML-related deaths in Peru and to develop strategies that improve patient outcomes. Disclosures No relevant conflicts of interest to declare.

AML-116: Examining Healthcare Resource Utilization (HCRU) and Costs in US Patients Diagnosed with Relapsed Acute Myeloid Leukemia (AML)

Context AML is the most common form of acute leukemia in adults. The age-adjusted incidence of AML in the USA is 4.3/100,000 people, with median age of 68 years at diagnosis. Following diagnosis, treatment options include intensive induction chemotherapy to induce remission (followed by post-remission therapies, including high-dose cytarabine-based regimens and hematopoietic stem cell transplantation), less intensive induction treatment, or supportive care. Prognosis following relapse is poor, with median survival of 8–10 months; studies show much of this time is spent in inpatient or outpatient settings. Objective To examine HCRU, particularly inpatient hospitalizations and associated costs, in relapsed AML patients. Design A retrospective analysis was conducted using the Premier Healthcare Database, a hospital administrative database containing >1 billion inpatient and outpatient encounters in the USA. ICD-10-CM codes for AML in relapse-identified adult patients enrolled in the database between January 1, 2016 and March 31, 2019. The index date was the first relapse encounter date. Patients Patients were followed until inpatient death, or last inpatient discharge date/hospital-based outpatient visit, before the end of study period (September 30, 2019). Main outcome measures Demographics, comorbidities, inpatient and intensive care unit (ICU) admissions, length of stay (LOS), and costs. Results 2,290 patients were identified; mean age was 61.2 years (median 65.0) and 46.9% were female. Primary insurance coverage was Medicare (51.2%), commercial (29.1%), Medicaid (13.8%), or other (5.9%). Common comorbidities were diabetes (31.0%), chronic heart failure (19.5%), and chronic obstructive pulmonary disease (19.0%). Patient follow-up varied from Conclusions The results demonstrate the substantial HCRU burden and costs shouldered by patients and payers following diagnosis of relapsed AML. Though not assessed here, there is potential value in therapies that delay relapse and improve survival in AML patients. The study was supported by Bristol-Myers Squibb.

Outcomes and health care utilization of older patients with acute myeloid leukemia

BackgroundThe incidence of acute myeloid leukemia (AML) in older patients is increasing, but practice guidelines balancing quality-of-life, time outside of hospital and overall survival (OS) are not established. MethodsWe conducted a retrospective analysis comparing time outside hospital, OS and end-of-life care in AML patients ≥60 years treated with intensive chemotherapy (IC), hypomethylating agents (HMA) and best supportive care (BSC) in a tertiary hospital. ResultsOf 201 patients diagnosed between 2005 and 2015, 54% received IC while 14% and 32% were treated with HMA and BSC respectively. Median OS was significantly higher in patients treated with IC and HMA compared with BSC (11.5 versus 16.2 versus 1.3 months; p < .0001).Median number of hospital admissions for the entire cohort was 3 (1–17) and patients spent <50% of their life after the diagnosis in the hospital setting. Compared to BSC, IC (HR 0.27, p < .0001) and HMA therapy (HR 0.16, p < .0001) were associated with the lower likelihood of spending at least 25% of survival time in hospital.Although 66% patients were referred to palliative care, the interval between referral to death was 24 (1–971) days and 46% patients died in the hospital. ConclusionOlder patients with AML, irrespective of treatment, require intensive health care resources, are more likely to die in hospital and less likely to use hospice services. Older AML patients treated with disease modifying therapy survive longer than those receiving BSC, and spend >50% of survival time outside the hospital. These data are informative for counselling older patients with AML.

Abstract A04: Childhood cancer incidence among specific Asian and Pacific Islander populations in the U.S.

Abstract Background: We sought to explore variation in childhood cancer incidence rates among specific Asian and Pacific Islander (API) groups. Despite high genetic diversity in this region of the world, API groups in the United States are often combined into a single race/ethnic group. Methods: The Surveillance, Epidemiology, and End Results (SEER) Detailed Asian/Pacific Islander (2000-Centered) data was used for this analysis. Cancer diagnoses occurring between January 1998 to December 2002 from 14 SEER registries were included. Detailed racial/ethnic population data from the 2000 census was used to calculate incidence rates for individual races with at least 500,000 individuals. We also combined this data into groups based on geographic regions and genetic similarity, which included East Asia (China, Japan, Korea; n=377 cases), Southeast Asia (Vietnam, Laos, Cambodia; n=136 cases), Asian Indian/Pakistan (n=163 cases), Oceania (Guam, Samoa, Tonga; n=29 cases), and the Philippines (n=199 cases). Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated comparing each API regional group to non-Hispanic Whites (NHW), and each API regional group to East Asians. Results: Incidence rates among detailed Asian and Pacific Islander groups varied. Acute lymphoblastic leukemia (ALL) was significantly lower in children of SE Asian (IRR 0.59, 95% CI 0.42, 0.82) and Filipino (IRR 0.73, 95% CI 0.57, 1.00) descent compared to non-Hispanic Whites. Acute myeloid leukemia (AML) was more common among children from Oceania compared to NHW (IRR 3.44, 95% CI 1.63, 7.28). Central nervous system (CNS) cancers were less common among East Asian (IRR 0.74, 95% CI 0.58, 0.96), SE Asian (IRR 0.45, 95% CI 0.28, 0.73), and Filipino (IRR 0.48, 95% CI 0.32, 0.72) children compared to NHW. When comparing the incidence of cancers among API regions, few clear patterns emerged. The incidence of AML in children from Oceania was nearly four times that in East Asians (IRR 3.88, 95% CI 1.64, 9,.11), though roughly the same among all other regions. The incidence rates of ALL (IRR 0.63, 95% CI 0.41, 0.97) and malignant gonadal germ cell tumors (IRR 0.29 95% CI 0.08, 0.97) were lower in SE Asians compared to East Asians. Lymphoma was twice as common in Asian Indians/Pakistani children compared to East Asians (IRR 2.13, 95% CI 1.33, 2.29). Conclusions: The variation observed in cancer incidence patterns among these groups is important and may indicate differences in underlying etiology and/or exposure patterns. These findings highlight possible disparities in cancer incidence between specific API groups. Citation Format: Kristin J. Moore, Aubrey K. Hubbard, Lindsay A. Williams, Logan G. Spector. Childhood cancer incidence among specific Asian and Pacific Islander populations in the U.S. [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A04.

Abstract A06: Impact of cigarette smoke exposure on acute myeloid leukemia progression

Abstract Cigarette smoke is known to cause lung cancer but is also associated with increased incidence of leukemia. Acute myeloid leukemia (AML) is the most lethal form of leukemia, and patients who are or were smokers have increased risk of developing AML and have worse prognosis. There is also an increased incidence of AML in children whose parents smoked either during or after the pregnancy. It is currently unknown how cigarette smoke exposure (CSE) may be impacting leukemic progression or treatment efficacy in AML. Cigarette smoking increases levels of reactive oxygen species (ROS) in the tissue of smokers, including peripheral blood samples. Oxidative stress can alter epigenetic signaling, including DNA methylation. Oxidation of methylated DNA and oxidative lesions on DNA can alter normal DNA methylation patterns. Smokers have altered DNA methylation that can be retained decades after the cessation of the habit, and these changes can be found in the blood cells of smokers. Cigarette smoke condensate (CSC) treatment has also been seen to epigenetically prime nontransformed human bronchial cells for malignant transformation. These occurrences have been seen in the context of lung cancer and lung damage, but studies into other tissue damage have largely been overlooked. Thus, we hypothesize that CSE impacts leukemic progression and treatment in AML through these mechanisms. We have developed a model to study the impact of CSE on AML in mice. NOD-SCID mice are smoke exposed for two weeks prior to being engrafted with luciferase-labeled human AML cells. The CSE is performed in the SCIREQ Cigarette Smoking Robot, with 3R4F research cigarettes 5 days/week. We include experimental arms of smoking cessation (who stop once evidence of leukemic engraftment is detected) and continued smoking, to model patients who either stop or continue smoking upon diagnosis of AML. Leukemic burden is quantified through bioluminescent imaging throughout the experiment. From these models, we have observed that two weeks of CSE is sufficient to significantly increase (p-value&amp;lt;0.0001) early leukemic burden as compared to non-smoke exposed mice, in FLT3-ITD AML-bearing mice. Spleen samples revealed trends of increased levels of superoxides in the CSE mice. Currently, immunohistochemistry is being performed on collected organs to detect oxidative stress markers. Additionally, mouse spleen DNA underwent reduced representative bisulfide sequencing; the levels of DNA methylation in the mouse host cells and in the leukemia are compared between our CSE groups. This is the first description of CSE promoting leukemia growth in mouse model, which will enable the study of mechanistic aspects. This may help define if unique treatment strategies are needed for these patients. Citation Format: Yue Lu, Marcos Estecio, Marina Konopleva, Elias Jabbour, Joya Chandra, Mary Figueroa. Impact of cigarette smoke exposure on acute myeloid leukemia progression [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A06.

Demographic and pattern of childhood acute leukemia in Duhok, Kurdistan region of Iraq, 2009-2018

Background and objectives: Leukemia is a common childhood cancer, constituting more than 25% in many pop- ulations. The most frequent type of childhood leukemia is acute lymphoblastic leukemia. The aim of this study is to describe the annual incidence, rate and demographics of acute childhood leukemia and their patterns in Duhok, Kurdistan - Iraq, in the period from 2009 to 2018. Methods:It is a retrospective study that was conducted at Heevi Pediatric Teaching Hospital in Duhok. A total of 198 patients, who were diagnosed as new cases of acute leukemia and were less than 15 years of age in the past ten years (from 2009 to 2018), were included in this study. Demographic data and the presenting hematological values of acute leukemia, based on cytomorphologic characteristics of bone marrow leukemic blast cells, were studies. Results: Childhood acute leukemia represented about 40 % of the total percentage of cancers among children in Duhok. It was more predominant in boys (53.5%) than in girls (46.5%). The cases peaked at 2-10 years cohort (69.2%). The number of cases ranged from 17 cases in 2009 to 15 cases in 2018 and reached a peak of 31 cases in 2016. The most prevalent type of leukemia was Acute Lymphoblastic Leukemia (ALL) (161 cases, 81.6%), followed by Acute Myeloid Leukemia (37 cases, 18.4%). The overall annual incidence rate was 2.0 cases /100,000 per year. The yearly incidence rates of leukemia were 1.3 – 2.4 cases /100,000. The highest incidence rate was in Duhok center (2.4 cases /100,000) and Zakho (2.3 cases /100,000); however, the least incidence rate was in Amedi (1.3 cases /100,000). The incidence of ALL appears to be nearly fourfold higher than the incidence of Acute Myeloid Leukemia in different areas of Duhok. Conclusions:It was found that childhood acute leukemia had lower prevalence in Duhok, and the clinical hematological features were similar to that of other studies.

Role of epigenetic regulators in single-base substitution patterns in AML.

e19500 Background: Incidence of Acute Myeloid Leukemia (AML) increases with age, as does Clonal Hematopoiesis of indeterminate Potential (CHiP), wherein specific genes are mutated in healthy individuals. Single Base pair Substitutions (SBS) are associated with aging and AML, most commonly C&gt;T. G&gt;A transitions are found in a similar prevalence in all age groups, although the number of mutations are higher in older age groups and associated with therapy. Determining a pattern of SBS in leukemia that is distinct from aging has been a challenge. Methods: We performed mutational signature analysis on 10,152 mutations in 3,575 unique suspected AML patient bone marrow, peripheral blood, or FFPE tissue samples. Samples were evaluated using an all exon amplicon based 27 gene next generation sequencing panel. The cohort was divided into 5 groups based on age (0-14, 15-39, 40-54, 55-65, and &gt;65 years), as well as into three gene mutation groups 1) TET2 WT (n=7,479 mutations), 2) TET2/DNMT3A WT (n=6,701) and 3) TET2/DNMT3A WT with chromatin regulators WT (ASXL1, ATRX, BCOR, BCORL1, EZH2, PHF6, RAD21, SMC1A, SMC3, STAG2; n=3627 mutations). Results: Predominant SBS were C&gt;T (42.7%) and G&gt;A (59.0%) transitions across all age groups. The percentage of C&gt;T SBS increased with age: 0-14 years cohort (18.0% of cases; 1.5% of mutations) to &gt;65 years cohort (58.8% of cases; 39.6% of mutations). There was no significant change in the prevalence of G&gt;A mutations with age, however, the total number of mutations did increase with age (0-14 0.2% vs &gt;65 39.6%). In each of the gene mutation groups, the number of C&gt;T and G&gt;A total mutations decreases as TET2 MT (42.7% and 59.0%), TET2 WT (27.0% and 45.1%), TET2/DNMT3A WT (20.8% and 34.3%), and TET2/DNMT3A WT with WT chromatin regulators (10.1% and 25.5%). Conclusions: In this study, both the prevalence and number of mutations in AML patients increases with age for C&gt;T transitions, but for G&gt;A transitions only the number of mutations increases with age, consistent with previously reported studies. In this data set, by removing mutations in TET2, TET2 and DNMT3A, TET2 and DNMT3A with genes that regulate chromatin accessibility, the number of C&gt;T and G&gt;A transitions decreases in order of effect, with the chromatin modifiers having the largest effect. The effect of removing these mutations suggests a mechanism driving leukemogenesis whereby DNMT3A methylates cytosine, TET2 deaminates this methylated cytosine, and finally chromatin modifiers regulate accessibility to these methylation sites, thereby modulating downstream oncologic pathways.

Economic and Clinical Burden of Acute Myeloid Leukemia Episodes of Care in the United States: A Retrospective Analysis of a Commercial Payer Database.

In the United States, the incidence of acute myeloid leukemia (AML) has steadily increased over the last decade; in 2019, it was estimated that AML would affect 21,450 new patients and lead to 10,920 deaths. Detailed real-world cost estimates and comparisons of key AML treatment episodes, such as in high-intensity chemotherapy (HIC), low-intensity chemotherapy (LIC), hematopoietic stem cell transplantation (HSCT), and relapsed/refractory (R/R), are scarce in the commercially insured U.S. To examine health resource utilization (HRU), clinical burden, and direct health care costs across various AML treatment episodes in a large sample of commercially insured U.S. A retrospective cohort analysis was conducted. Patients with newly diagnosed AML were followed to identify the key active treatment episodes across the course of their disease. Data were obtained from 2 sources: IQVIA's Real-World Data (RWD) Adjudicated Claims Database - U.S. (formerly known as PharMetrics Plus), which comprises adjudicated claims for more than 150 million unique enrollees across the United States, and IQVIA Charge Detail Master Hospital Database, which has detailed data regarding services received in an inpatient setting. Calculation of all-cause HRU was based on physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Calculation of all-cause health care costs was based on total allowed costs and reported by the following cost components: physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Symptom and toxicity events were estimated via proxies such as diagnosis codes, procedures, and treatments administered. The final study sample consisted of 1,542 HIC-induction (HIC-I), 591 HIC-consolidation (HIC-C), 628 LIC, 1,000 patients with HSCT, and 707 patients with R/R AML. Total mean episode costs were highest in R/R episodes ($439,104), followed by HSCT ($329,621), HIC-I ($198,657), HIC-C ($73,428), and LIC ($53,081) episodes. Across all treatment episodes, hospitalization was the largest contributor to cost with mean hospitalization costs ranging from $308,978 in the R/R setting to $49,580 for patients receiving LIC; of these, costs related to intensive care unit admission were a noteworthy contributor. In patients with R/R AML and HSCT, expenditures related to pharmacy utilization averaged $24,640 and $12,203, respectively, and expenditures related to physician office visits averaged $10,926 and $6,090, respectively; these expenditures were much lower across other episodes. Across all categories of symptom and toxicity events, cardiovascular events was the only category of event that was a significant predictor of higher cost across all episodes. Symptom and toxicity events commonly associated with AML were associated with significantly increased costs, especially in R/R episodes. This resource utilization and direct health care cost analysis highlights the substantial economic burden associated with key AML treatment episodes in the United States, specifically during HIC-I, HSCT, and R/R episodes. This study was funded by Astellas Pharma. Astellas employees were involved in the study design, interpretation of data, writing of the manuscript, and the decision to submit the manuscript for publication. Pandya and Wilson are employees of Astellas Pharma U.S. Walsh was an employee of Astellas Pharma U.S. while the study was conducted. Chen, McGuiness, and Wade are employees of IQVIA, which received funding from Astellas Pharma U.S. Madeiros was employed at Stanford University while this study was conducted and received a consulting fee from Astellas for work on this study. Data discussed in this study were previously presented at the 59th Annual American Society for Hematology Meeting & Exposition, 2017; December 9-12, 2017; Atlanta, GA.

Oral adherence in adults with acute myeloid leukemia (AML): results of a mixed methods study.

The incidence of AML is increasing, in part due to an aging population. Since 2017, eight novel agents have been introduced, 6 of which are oral: midostaurin, enasidenib, ivosidenib, gilteritinib, glasdegib, and venetoclax. With an increase in oral medications (OMs), patients face associated side effects that accompany OMs, which often decreases adherence. We aimed to identify and summarize adherence to OMs in this population. Our mixed method design used focus groups (FG) and patient surveys. After IRB approval, 11 patients and 4 caregivers participated in 4 FGs. Themes from the FGs were used to develop a 37-item OMs adherence needs assessment. Participants were recruited and consented at three cancer centers to complete surveys (online, at the clinic, hospital, or from home). A total of 100 patients completed OMs survey. The number of pills to be taken was the most frequent and troublesome challenge. The most frequently reported interventions that would improve patient adherence were smaller pills, easier packaging, and scheduling assistance. Nearly 33% of patients indicated they skip OMs dose altogether when they forget to take it. Younger patients (< 65years) were more accepting of taking oral compared with intravenous medications (p = .03). This study represents the first assessment of OMs adherence in adults with AML. Findings provide the basis for further exploration of interventions to enhance and increase adherence to OMs regimens.

Acute Myeloid Leukemia in Patients Living with HIV Infection: Several Questions, Fewer Answers.

Both human immunodeficiency virus (HIV) infection and acute myeloid leukemia (AML) may be considered relatively uncommon disorders in the general population, but the precise incidence of AML in people living with HIV infection (PLWH) is uncertain. However, life expectancy of newly infected HIV-positive patients receiving anti-retroviral therapy (ART) is gradually increasing, rivaling that of age-matched HIV-negative individuals, so that the occurrence of AML is also expected to progressively increase. Even if HIV is not reported to be directly mutagenic, several indirect leukemogenic mechanisms, mainly based on bone marrow microenvironment disruption, have been proposed. Despite a well-controlled HIV infection under ART should no longer be considered per se a contraindication to intensive chemotherapeutic approaches, including allogeneic hematopoietic stem cell transplantation, in selected fit patients with AML, survival outcomes are still generally unsatisfactory. We discussed several controversial issues about pathogenesis and clinical management of AML in PLWH, but few evidence-based answers may currently be provided, due to the limited number of cases reported in the literature, mainly as case reports or small retrospective case series. Prospective multicenter clinical trials are warranted to more precisely investigate epidemiology and cytogenetic/molecular features of AML in PLWH, but also to standardize and further improve its therapeutic management.

Age-Related Co-Expression of BCOR and BCORL1 mRNA in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy caused by a variety of genetic abnormalities and epigenetic dysregulation. The incidence of AML is strongly related to age, with the highest incidence rates being in older adults. The loss of function mutations in BCOR and BCORL1 genes have been identified in AML. BCL6 corepressor (BCOR) and BCL6 corepressor like 1 (BCORL1) are important epigenetic regu-lators as a member of Polycomb repressive complex 1 (PRC1.1), involved in histone modification processes. We analyzed the BCOR and BCORL1 mRNA expression in 74 adult and 22 pediatric patients with AML by Real-Time quantitative PCR in this study. Our results indicated that both BCOR and BCORL1 mRNA expressions decrease with age (p = 0.009 and p = 0.008, respectively) and there is a positive correlation between BCOR and BCORL1 mRNA expression (p < 0.001). BCOR and BCORL1 mRNA expressions were not significantly different in both adult and pediatric patients with AML compared to control (p > 0.05). Our findings indicate that expression of BCOR and BCORL1 mRNA are down-regulated with age. The increase in AML incidence with age suggests that age-associated BCOR and BCORL1 down-regulation might potentially contribute to age-related epigenetic alterations and form a predisposing condition for the development of elderly AML.

Assessing Efficacy and Safety of Daunorubicin and Cytarabine Liposomal in Patients with Acute Myeloid Leukemia

Background. Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The median age of diagnosis is 67 years old, and it has unfavorable outcomes in older patients. Approximately one-third of patients are diagnosed after the age of 75. Thus, as the population continues to increase in age, the incidence of AML will continue to expand (NCCN guidelines: AML. Version 3.2019). The long term disease free survival (DFS) rates for patients &gt; 60 years of age is 5-15% whereas younger patients &lt; 60 years of age have a better DFS rate of up to 40% (Dohner H, et al. N Engl J Med. 2015). Recent advancements have been made in patients with AML, including the approval of daunorubicin and cytarabine liposomal (Vyxeos®) for the treatment of adults with 2 poor risk types of AML: newly diagnosed therapy related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Given the financial constraints of this new medication, our objective was to determine the safety and efficacy of daunorubicin and cytarabine liposomal in our adult patients with t-AML and AML-MRC at a single academic medical center. Methods. This was a single center, retrospective, chart review at Wake Forest Baptist Health (WFBH) Comprehensive Cancer Center from August 1, 2017 to November 1, 2018. Patients were selected via report generation if they had received at least one dose of daunorubicin and cytarabine liposomal during the study period. The initial induction dose of daunorubicin and cytarabine liposomal was 44 mg/m2 of daunorubicin and 100 mg/m2 cytarabine administered on days 1, 3, and 5 for up to 2 cycles to achieve remission. If a second induction was necessary, the same induction doses were given on days 1 and 3 only. The consolidation dose was 29 mg/m2 of daunorubicin and 65 mg/m2 of cytarabine on days 1 and 3 for up to 2 cycles. The primary endpoint was overall survival (OS). Secondary endpoints included event free survival (EFS), 30-day and 60-day mortality, complete remission (CR) and morphologic complete remission with incomplete blood count recovery (CRi), adverse drug reactions, and financial impact to the health system. Descriptive statistics were utilized for demographic data. Time to event data was analyzed using the Kaplan-Meier method. SPSS IBM and Microsoft Excel Software were utilized for data analysis. Results. A total of 37 AML patients were identified as receiving daunorubicin and cytarabine liposomal from August 2017 to November 2018. Of those 37 patients, 27 had AML-MRC and 10 had t-AML. The average patient was a 70 year old Caucasian male with an ECOG performance status of 1 and a Charlson Comorbidity Index of 6 (Table 1). The median OS was 10 months and EFS was 7 months. The 30-day mortality rate was 16% and 60-day mortality rate was 19%. Eighteen patients (49%) achieved a CR and 2 patients (5%) achieved a CRi. A subgroup analysis was conducted for prior hypomethylating agent (HMA) use, age &gt; 75 years old, &lt; 60 years old, molecular mutations including FLT3-ITD and TP53 mutations, and t-AML. Poorer outcomes were noted in patients &gt; age 75, prior HMA use, and the t-AML subgroups. Table 3 highlights the OS, 60-day mortality rate, transplant received and CR+CRi for each subgroup. The median time to platelet and absolute neutrophil count (ANC) recovery was 32 and 33 days, respectively. Eight patients (21.6%) proceeded to transplant post administration of daunorubicin and cytarabine liposomal. All patients experienced at least one adverse event with hematologic being the most commonly observed toxicity (Table 4). Most patients received induction therapy with daunorubicin and cytarabine liposomal in the inpatient setting whereas consolidation was predominantly administered in an outpatient encounter. Conclusions. Daunorubicin and cytarabine liposomal was considered an effective treatment option for patients with t-AML and AML-MRC with a CR+CRi rate of 54%. Younger patients (&lt; 60 years old) exhibited the greatest benefit with an OS of 12 months and 60 day mortality rate of 0%. However, poorer outcomes were demonstrated in elderly patients (&gt; 75 years old), patients with FLT3-ITD positive mutations, and patients with previous HMA use, with an OS less than 2 months in each subgroup and mortality rates ranging up to 60%. Thus, additional studies are necessary to determine the role of daunorubicin and cytarabine liposomal in these higher risk patient subgroups &gt; age 75, FLT3-ITD positive patients, and patients with previous HMA use. Disclosures Manuel: Novartis: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. Pardee:Rafael Pharmaceuticals: Consultancy, Research Funding; Karyopharm: Research Funding; Spherix Intellectual Property: Research Funding; Pharmacyclics/Janssen: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; CBM Bipharma: Membership on an entity's Board of Directors or advisory committees. Powell:Janssen: Research Funding; Rafael Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding.

The Relationship between Hospitalization and Patient-Reported Outcomes (PROs) in Patients with FLT3-Mutated (FLT3mut+) Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML): Results from the Phase 3 Admiral Study

The Relationship between Hospitalization and Patient-Reported Outcomes (PROs) in Patients with FLT3-Mutated (FLT3mut+) Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML): Results from the Phase 3 Admiral Study

In-Hospital Morbidity and Mortality Among Acute Myeloid Leukemia Patients Admitted for Hematopoeitic Stem Cell Transplants between 2002-2014

Introduction: Acute myeloid leukemia (AML) is a disease with poor overall prognosis, about 4.3 per 100,000 men and women per year are diagnosed with AML with a deaths rate of 2.8 per 100,000. The incidence of AML increases with age which leads to an older population with multiple comorbidities and inferior prognosis. Hematopoietic stem cell transplant (HCT) remains the standard of care in most intermediate and high-risk AML patients. However, HCT puts these patients at risk of severe cytopenia, opportunistic infections, acute graft versus host disease and financial stress, especially in the early phases of transplant. The purpose of this study is to identify the annual trends in in-hospital mortality and morbidity associated with patients with AML admitted for HCT and impact of comorbid conditions on the likelihood of death during admission. Method Data was collected from the National Inpatient Sample from the years of 2002 to 2014. Admissions for HCT for acute myeloid leukemia patients were identified using a procedural clinical classification software code for bone marrow transplants in combination with ICD 9 codes for acute myeloid leukemia. Annual trends in mortality, hospital length of stay, and costs of admission were assessed with a linear regression analysis. Univariate logistic regression analysis was used to test for associations between chronic medical conditions and mortality among these patients. Co-morbid conditions were identified using the Agency for Healthcare Research and Quality comorbidity measures for underlying chronic conditions in patients in 2013 to 2014. Results: Between and including the years of 2002 to 2014, a total weighted estimate of transplants for acute myeloid leukemias in the United States totaled 31,811 (N=6,102). Annual transplants increased from 1,761 in 2002 to 3,030 in 2014. In-hospital mortality decreased from 8.4% in 2002 to 4.8% in 2014 (p=0.02). The mean length of stay remained unchanged from 32.8 days in 2002 to 32.7 days in 2014. Costs of admission increased from $226,280 to $474,106. In-hospital mortality in the years 2013 and 2014 were most strongly associated with comorbid conditions of congestive heart failure (Odds ratio (OR)=5.93), weight loss (OR=4.32), coagulopathy (OR=3.84), liver cirrhosis (OR=3.41). Any two of these conditions increased the OR to 8.34. Conclusions: HCTs have traditionally been associated with high upfront including in-hospital mortality. Our data demonstrates that in the last two decades mortality has been reduced by almost 50% while the length of hospital stay has not changed. This could be related to improvements in supportive care and better selection of conditioning regimens for the patients. It also shows that the costs of hospitalization has doubled. Congestive heart failure, weight loss, underlying coagulopathy and liver cirrhosis are most strongly associated with worse outcomes with any combination of these further potentiating risk of death. Careful selection of patients with special attention to the pre-existing comorbidities is the key to improving early outcomes in HCT. Consideration should also be given to expanding infrastructure to perform outpatient transplants to bend the cost curve. Disclosures No relevant conflicts of interest to declare.