scholarly journals Evaluation of Early Discharge after Intensive Induction Chemotherapy in Adults with Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4043-4043
Author(s):  
Amanda Al-Bahou ◽  
Katherine A. Richter ◽  
Matthew Snyder ◽  
Sarah J. Rockwell ◽  
Seongseok Yun ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Hospital Readmission ◽  
Myeloid Leukemia ◽  
Early Discharge ◽  
Optimal Time ◽  
Hospital Days ◽  
Length Of Hospitalization ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) patients who require intensive induction chemotherapy are traditionally hospitalized for the duration of neutropenia to monitor for treatment-related toxicities. On average, AML patients are hospitalized for 33.7 days during first induction treatment (Sacks et al Clin Ther 2018). Prolonged hospitalizations are associated with substantial costs, increased risk for nosocomial infections, and significant declines in physical function and quality of life. Several studies have evaluated the impact of early discharge prior to neutrophil recovery, however current evidence has not clearly defined the ideal patient characteristics or described the optimal time post-induction to safely discharge patients. At our institution, we established a "STREAMLINE (Safe TRansition with Early-discharge in Acute Myeloid Leukemia INtensivE-induction) Protocol" to evaluate patients for early discharge following induction chemotherapy. Objective: To determine the optimal time after induction chemotherapy to safely discharge AML patients. Methods: Retrospective, single-institution review of adult AML patients who received intensive induction chemotherapy from January 1, 2017 to December 31, 2019. The STREAMLINE criteria for early discharge (Table 1) was retrospectively applied at discharge timepoint-1 (DT1) and discharge timepoint-2 (DT2). DT1 was defined as within 24 hours following completion of induction therapy and DT2 was defined as within 24 hours after performance of first bone marrow biopsy after induction therapy. Each patient served as his/her own control to compare actual length of hospitalization to the length of hospitalization if the patient had been discharged at DT1 and/or DT2. The primary outcome was number of hospital days saved if discharged at DT1 compared to DT2. Secondary outcomes included proportion of patients who met STREAMLINE criteria, incidence and time to first complication that would require hospital readmission for patients who met criteria, overall days of hospitalization, and overall survival at 30 and 60 days. Results: A total of 284 patients met inclusion criteria and were assessed for early discharge. Eighty-nine patients (31.3%) met the STREAMLINE criteria for early discharge with 51 (57.4%) at DT1, 19 (21.3%) at DT2, and 19 (21.3%) at DT1 and DT2. Baseline demographics of the study population are described in Table 2. Of the 195 patients (68.7%) ineligible for early discharge, 118 (60.5%) were ineligible due to an active medical issue or laboratory parameter not met, 60 (30.8%) due to age, 9 (4.6%) due to poor performance status, and 8 (4.1%) due to history or evidence of heart failure. The most common laboratory or active medical issues that led to ineligibility were the need for intravenous anti-infectives (34.9%), fever within 48 hours of discharge timepoint (29.3%), and transfusion dependence (24.5%). Study outcomes are summarized in Table 3. In the 70 patients who met STREAMLINE criteria at DT1, 60 (94.3%) experienced an event that would require hospital readmission (Figure 1). The most common were neutropenic fever (42.9%), proven infection (31.4%), and re-induction therapy (7.1%). The median time to readmission event was 6 days [interquartile range (IQR) 3-10]. Based on early discharge at DT1, median length of hospitalization was 26 days (IQR 19-33) with a median 6 days saved (IQR 2-9.8). In the 38 patients who met STREAMLINE criteria at DT2, 26 (68.4%) experienced an event that would require hospital readmission (Figure 1). The most frequent were neutropenic fever (28.9%), re-induction therapy (18.4%), and proven infection (13.2%). The median time to readmission event was 3 days (IQR 2-5). Based on early discharge at DT2, the median length of hospitalization was 25.5 days (IQR 22-40) with a median 3 days saved (IQR 1-5). Overall, early discharge at DT1 was predicted to save a total of 468 days compared to a total of 165 days at DT2. In all patients who met STREAMLINE criteria (n=89), overall survival at 30- and 60-days post-induction therapy was 100%. Conclusions: Early discharge at DT1 was predicted to save a greater number of hospital days compared to DT2, however DT1 was associated with higher readmission events. These findings suggest that early discharge is safe and feasible in AML patients who receive intensive induction therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

2021 ◽  
Vol 10 ◽  
pp. e2288
Author(s):  
Mahdiyar Iravani Saadi ◽  
Mani Ramzi ◽  
Aliasghar Karimi ◽  
Maryam Owjfard ◽  
Mahmoud Torkamani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Quantitative Polymerase Chain Reaction ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Before And After ◽  
Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

Early discharge after induction chemotherapy for acute myeloid leukemia: Safety outcomes and hospital readmissions.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 6532-6532
Author(s):  
Nikita V. Baclig ◽  
Sarah A. Buckley ◽  
Anna B. Halpern ◽  
Paul C. Hendrie ◽  
Mary-Elizabeth M. Percival ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Hospital Readmissions ◽  
Early Discharge ◽  
Safety Outcomes ◽  
Acute Myeloid

scholarly journals Peripheral Blood Blast Clearance As an Independent Predictor of Clinical Response and Outcomes in Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2684-2684
Author(s):  
Noa G. Holtzman ◽  
Firas El Chaer ◽  
Omer Ali ◽  
Ameet Patel ◽  
Maria R. Baer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcomes ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Total Leukocyte Count ◽  
Risk Category ◽  
The Absolute ◽  
Acute Myeloid

Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease that depends on precise risk-stratification for predicting outcomes and optimizing therapy plans. Despite the current clinical landscape of incorporating karyotype and mutations into prognostic models, chemosensitivity (or lack thereof) is usually not evaluated or appreciated until a patient undergoes a day 14 bone marrow (D14BM) evaluation during induction treatment. While the D14BM aspirate and biopsy are regularly used to predict achievement of CR versus need for further reinduction therapy, some have questioned its utility. Further, the invasive nature of the procedure leads to significant patient discomfort, anxiety, increased risk of complications (infections, bleeding, damage to surrounding tissues) and, at times, is not feasible due to a patient's critical state. Therefore, alternative criteria are needed to help risk-stratify these patients and predict treatment responses. We report here a single center analysis of the relationship between the rate of peripheral blood blast (PBB) clearance with cytotoxic induction therapy and clinical outcomes. Methods Patients diagnosed with AML (non-M3) with detectable PBB via manual differential or flow cytometry at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC) during 2007-2018 were identified. Only patients who underwent induction with a "7+3" regimen with cytarabine and an anthracycline (idarubicin or daunorubicin), or "7+3" plus a third agent, were included. Patient and disease characteristics, treatment courses, and clinical outcomes were collected. The absolute PBB count was calculated by percent PBB multiplied by total leukocyte count (103/mcL). PBB rate of clearance (PBB-RC) was defined as the percentage of the absolute PBB count at diagnosis that was cleared each day, on average, until clearance or D14 of induction chemotherapy. Patients were divided into three groups based on PBB-RC: high, if PBB-RC >30% (n=15); low, if PBB-RC <10% (n=16); and intermediate, if PBB-RC fell between 10-30% (n=133). Primary outcomes included D14BM status, achievement of complete remission (CR) with or without full count recovery, and overall survival (OS). Multivariate logistic regression and Cox proportional hazards models were conducted and adjusted for the disease risk category, age, sex, ethnicity, and use of leukapheresis or hydroxyurea. Cox models were also adjusted for allogeneic stem cell transplantation (SCT) status. Results Treatment-naive AML patients with PBB at diagnosis and who underwent cytotoxic induction therapy were identified (n=164). Patient characteristics are shown in Table 1. Sixty-eight percent of patients underwent induction with "7+3", and 28% with "7+3" with a third agent. Pre-induction leukoreduction included hydroxyurea (29%) and/or leukapheresis (12%). Most (68%) patients received only one course of induction; 18% received 2 courses, and 8% received ≥3. Chemoablation on D14BM was achieved in 70% of patients (n=113); 27% (n=45) had residual disease, and 4% (n=6) were indeterminate. CR was achieved in 74% of patients (n=121), 19 of which required ≥ 2 induction courses. Forty-one patients proceeded to SCT. Median OS was 18.5 months (range 0.5-122). Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR=1.97; 95% CI: 1.39-2.80, p<0.001). The adjusted area under the ROC curve of PBB-RC for predicting D14BM clearance was 0.72, with a positive predictive value (PPV) of high PBB-RC of 93% and negative PV (NPV) of low PBB-RC of 81%. PBB-RC was also significantly associated with CR (OR per 5% =2.08; 95% CI: 1.38-3.14, p<0.001). CR was achieved in all patients in the high PBB-RC group, while only 44% in the low PBB-RC group. PBB-RC was significantly associated with improved OS (HR per 5%=0.67; 95% CI: 0.52-0.85, Figure 1). Other factors associated with longer OS included favorable risk category (HR=0.03; 95% CI: 0.01-0.23) and SCT (HR=0.50; 95% CI: 0.26-0.95). African American patients had poorer OS adjusted for PBB-RC (HR=2.22; 95% CI: 1.16-4.25), while race was not associated with D14BM or CR rate. Conclusion PBB-RC during induction chemotherapy is predictive of achievement of CR and improved OS in AML. PBB-RC is also significantly associated with D14BM clearance and can therefore serve as a surrogate predictive marker for treatment response in AML patients with PBB at diagnosis. . Disclosures Emadi: NewLink Genetics: Research Funding.

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 479-485 ◽  
Author(s):  
Jacob M. Rowe ◽  
Donna Neuberg ◽  
William Friedenberg ◽  
John M. Bennett ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Growth Factor ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Gm Csf ◽  
Acute Myeloid

Abstract The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixty-two older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P = .03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate.

Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 3869-3876 ◽  
Author(s):  
Jeanne E. Anderson ◽  
Kenneth J. Kopecky ◽  
Cheryl L. Willman ◽  
David Head ◽  
Margaret R. O'Donnell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
P Value ◽  
Term Survival ◽  
Acute Myeloid

Complete remission and long-term survival rates are low for older adults treated for acute myeloid leukemia (AML). Because of favorable phase 2 data using mitoxantrone and etoposide, we conducted a phase 3 study (SWOG-9333) in which patients over 55 years of age with previously untreated AML were randomized to receive mitoxantrone (10 mg/m2 per day × 5) and etoposide (100 mg/m2per day × 5) [ME], or cytarabine (200 mg/m2 per day × 7) and daunorubicin (45 mg/m2 per day × 3) [AD] as induction therapy. The randomization was stratified by age, onset of leukemia, and multidrug resistance phenotype. Over a 4-year period, 328 eligible patients from 66 institutions were enrolled. The complete remission rate was 34% (95% confidence interval [CI] 26%-41%) for patients in the ME and 43% (CI 35%-51%) for patients in the AD treatment arm (one-tailedP value .96). The rates of resistant disease were 43% (CI 35%-51%) and 34% (CI 27%-42%), respectively, for the 2 treatment arms (one-tailed P value .95). The estimated overall survival at 2 years was 11% (CI 6%-15%) and 19% (CI 12%-25%) for patients randomized to ME and to AD induction therapy, respectively (one-tailed P value .99). After accounting for the independent prognostic factors associated with survival (karyotype, performance status, age, white blood cell count), exploratory analysis suggested there was a worse survival for patients who received ME compared with AD induction therapy (2-tailed P value .0066). We conclude that the results of our study do not demonstrate any benefit to the use of ME induction chemotherapy instead of AD in older patients with AML.

Incidence and Prognostic Factors for Infectious and Hemorrhagic Death in Patients with Acute Myeloid Leukemia: A Single-Centre Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4300-4300 ◽  
Author(s):  
Pau Montesinos ◽  
Guillermo Martin ◽  
Ninotchka Mendoza ◽  
Jesus Martinez ◽  
Federico Moscardo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Induction Failure ◽  
Acute Myeloid

Abstract INTRODUCTION: Death is as a common cause of remission induction failure in patients with acute myeloid leukemia (AML), mainly due to hemorrhage and infection. The relative incidence and chronology of each of these categories of induction failure, as well as their prognostic factors, have been investigated critically and in detail in rare studies only. OBJECTIVES: We report the incidence, chronology, and prognostic factors for induction death, analyzing separately hemorrhagic and infectious death, in a large series of 946 patients with AML who received induction therapy in a single institution over the last 30 years. PATIENTS AND METHODS: Adult patients were consecutively diagnosed of AML and started first induction chemotherapy in our institution. AML was classified according to the FAB criteria. Induction therapy consisted of the classic combination of cytarabine and anthracyclines (with or without a third agent) in 50% of patients, cytarabine plus adriamicine and thioguanine or vincristine in 17%, ATRA with chemotherapy in 9%, monochemotherapy with anthracycline in 7%, high dose cytarabine in 7%, and other regimens in 10%. Causes of induction death include the following categories: Infection, when death was due to a clinical, radiological or microbiologically documented infection, Hemorrhage, when a major bleeding occured in a vital organ (central nervous system, lungs). Gastrointestinal hemorrhage required massive melena or hematemesis accompanied by fall in blood pressure, and Other, i.e., any other cause not classified as infection or hemorrhage. RESULTS: From 1977 to 2007, 946 consecutive patients with diagnosis of AML received induction chemotherapy, 24% in the period 1 (1977–1986), 28% in the period 2 (1987–1993), 28% in the period 3 (1994–2000), and 20% in the period 4 (2001–2007). Median age was 55 years (range 13–83 years). One hundred and sixty-seven patients (18%) had antecedents of myelodysplastic/myeloprolipherative disease (10%) or other neoplasia (8%). Two hundred and thirty-seven patients (25%) died during induction therapy, 13% due to infection, 7% due to hemorrhage, 2% due to hemorrhage and infection, and 3% due to other causes. The induction mortality rates decreased gradually over the 4 periods (31% vs 24% vs 18% vs 18%), due to reduction of both hemorrhagic and non-hemorrhagic deaths. Overall, 42% of hemorrhagic deaths occurred within the first 10 days of induction therapy, whereas 86% of infectious deaths occurred after 10 days. In multivariate analysis, the following characteristics had an unfavorable impact on overall induction mortality: age >60 years, WBC >50x109/L, Quick index <65%, ECOG >1, and albumin serum levels <3.5mg/dL. Multivariate analysis identified the following factors predicting for infectious mortality: albumin <3.5mg/dL, age >50 years, AML secondary to neoplasia, ECOG >1, and fever at presentation. The following factors were associated with hemorrhagic mortality: WBC >50x109/L, FAB-M3, age >60 years, de novo AML, and ECOG >1. CONCLUSIONS: The main causes of induction death in AML patients, infection and hemorrhage, shows a different chronologic pattern and can be separately predicted by their own specific prognostic factors.

Randomized Clinical Trial of Induction Therapy Comparing Intensified Daunorubicin with Idarubicin in Patients with Previously Untreated De Novo Acute Myeloid Leukemia (JALSG AML201 Study).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2000-2000 ◽  
Author(s):  
Shigeki Ohtake ◽  
Shuichi Miyawaki ◽  
Hiroyuki Fujita ◽  
Hitoshi Kiyoi ◽  
Katsuji Shinagawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Standard Dose ◽  
Newly Diagnosed ◽  
Induction Regimen ◽  
To Receive ◽  
Acute Myeloid

Abstract We conducted a multicenter prospective randomized study to determine whether the intensified daunorubicin (DNR) induction chemotherapy would be as effective as idarubicin (IDR) in adult acute myeloid leukemia (AML). Newly diagnosed adult patients with AML excluding FAB-M3 were consecutively registered and randomized to receive either increased dose of DNR or standard dose of IDR induction chemotherapy. All patients received cytarabine 100mg/m2 daily for 7 days by continuous intravenous infusion, and either DNR 50mg/m2 daily for 5 days or IDR 12mg/m2 daily for 3 days according to randomization. If the patients did not achieve complete remission (CR) after the first induction therapy, the same induction therapy was given once more. Patients achieving CR were again randomized to receive either 3 courses of high-dose cytarabine or 4 courses of conventional multiagent consolidation therapy. The results of later randomization will be reported another abstract. From December 2001 to December 2005, 1064 newly diagnosed patients with de novo AML were registered and 1057 were eligible. Median age was 47 years old (range 15 to 64). Five hundred twenty five patients were randomized to DNR group, and 532 to IDR group. The two groups were well matched for pretreatment characteristics. CR was achieved in 407 patients (77.5%; 95% CI, 73.9% – 81.1%) with 321 (61.1%) after 1 induction course in DNR group and 418 patients (78.6%; 75.1% – 82.1%) with 341 (64.1%) after 1 course in IDR group (p = 0.68). Patients receiving IDR took slightly but significantly longer to recover from neutropenia and thrombocytopenia. There was a higher rate of sepsis in IDR (8.7%) than DNR (4.9%) (p = 0.02). The early death within 60 days occurred in 25 patients (4.7%) in IDR and 11 (2.1%) in DNR (p = 0.03). Logistic regression analysis revealed that induction regimen was not the independent prognostic factor, but CBF leukemia and the percentage of peroxidase positive leukemic blast were the significant independent factors for achieving remission. There was also no significant difference between the groups in the longer-time measures of efficacy: estimated overall survival at 4 years was 49.1% (42.4% – 55.8%) for DNR and 53.1% (47.6% – 58.6%)for IDR (p = 0.37); estimated relapse free survival at 4 years from CR was 42.2% (36.1% – 48.3%) for DNR and 41.8% (35.9% – 47.7%) for IDR (p = 0.62). The Cox proportional hazards analyses showed that the induction regimen did not affect these outcomes. In conclusion, increased dose of DNR and standard dose of IDR both achieve high remission rate and good long-term efficacy, and are equally effective for the treatment of AML patients up to 64 years, although the final assessment will have to be performed after longer follow up.

Comparison of Resource Utilization in Children Discharged Versus Children That Remain Hospitalized Following Chemotherapy for Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3697-3697
Author(s):  
Kelly D Getz ◽  
Tamara P. Miller ◽  
Alix E. Seif ◽  
Yimei Li ◽  
Yuan-Shung Huang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Resource Utilization ◽  
Myeloid Leukemia ◽  
Case Fatality ◽  
Early Discharge ◽  
Similar Data ◽  
Discharge Status ◽  
Hospital Days ◽  
Acute Myeloid ◽  
Count Recovery

Abstract Treatment for pediatric acute myeloid leukemia (AML) involves multiple courses of intensive chemotherapy leading to prolonged neutropenia with substantive infection risks. Patients are typically hospitalized at each course for the duration of chemotherapy and associated marrow aplasia. Evaluations of early discharge and outpatient supportive care in adult AML patients demonstrate comparable mortality and shorter lengths of stay compared to standard discharge. Similar data in the pediatric setting are limited. We used data from the Pediatric Health Information System (PHIS) to evaluate course-specific mortality and resource utilization in AML patients who were discharged prior to count recovery relative to comparable patients who remained hospitalized. We used a cohort of children treated for new onset AML at children's hospitals in the US contributing to PHIS. Analyses were restricted to patients considered eligible for discharge prior to count recovery. Patients were categorized at each course as early or standard discharge. Discharges within 3 days after chemotherapy completion were considered “early”. Course-specific follow-up started on the last day of chemotherapy and continued until the earliest of: start of the subsequent course, death, or 50 days after commencement of chemotherapy. Resource utilization was determined based on daily billing data and reported as days of use per 100 hospital days. Case fatality rates and duration of hospitalization were compared using chi-square and Wilcoxon rank sum tests. Poisson regression with inpatient days as offset was used to compare resource use by discharge status. The study population included 996 patients representing 2358 courses. Fewer patients were discharged early following Induction I (7%) compared to subsequent courses (22-24%). Rates of early discharge varied greatly by hospital ranging from 0% to 100%. Across courses, patients discharged early experienced 8-12 fewer inpatient days (all p<0.001) despite readmission rates >90%. Case fatality rates were low across courses (0-1.3%) and did not differ significantly by discharge status. However, more early discharge patients required ICU level care at each course (7.2-18.1%) compared to standard discharge patients (2.0%-8.7%; all p <0.02). Table 1 presents resource utilization by discharge status with corresponding rate ratios (RR). Rates of antibiotic, vasopressor, and oxygen therapy use were each consistently elevated for early discharge patients. Following Intensification I and II, blood product use was also higher among those discharged early. The data suggest a similar overall survival and shorter hospitalization following early compared to standard discharge. However, based on increased rates of vasopressor and antibiotic use, early discharge patients may be at greater risk for life-threatening chemotherapy-related infectious complications. Table 1: Resource utilization (per 100 hospital days) by Discharge Status Early Discharge Standard Discharge Adjusted1 RR (95% CI) Antibiotics Induction I 153.6 131.5 1.17 (1.00, 1.36)* Induction II 146.7 89.7 1.64 (1.48, 1.81)* Intensification I 144.2 95.1 1.52 (1.38, 1.67)* Intensification II 162.4 117.0 1.39 (1.27, 1.52)* Antifungals Induction I 78.9 91.6 0.87 (0.72, 1.05) Induction II 84.1 90.2 0.93 (0.86, 1.01) Intensification I 79.3 87.9 0.90 (0.82, 1.00) Intensification II 80.6 84.1 0.96 (0.86, 1.07) Antivirals Induction I 6.2 11.6 0.56 (0.20, 1.56) Induction II 4.0 5.9 0.58 (0.41, 1.11) Intensification I 8.7 13.1 0.66 (0.39, 1.12) Intensification II 5.7 13.0 0.44 (0.19, 0.98) Blood Products Induction I 34.6 29.9 1.16 (0.99, 1.35) Induction II 26.9 24.2 1.12 (0.99, 1.26) Intensification I 28.4 20.5 1.38 (1.11, 1.72)* Intensification II 39.1 29.1 1.34 (1.17, 1.55)* Vasopressors Induction I 2.4 0.4 6.47 (2.67, 15.7)* Induction II 3.5 0.7 5.04 (2.13, 12.0)* Intensification I 3.6 0.5 6.62 (2.91, 15.0)* Intensification II 3.8 1.0 3.69 (1.74, 7.83)* Parenteral nutrition Induction I 14.5 17.0 0.85 (0.43, 1.70) Induction II 10.3 9.5 1.09 (0.64, 1.86) Intensification I 7.5 6.1 1.24 (0.76, 2.02) Intensification II 11.0 8.4 1.30 (0.87, 1.96) Supplemental Oxygen Induction I 4.6 0.9 4.95 (1.87, 13.1)* Induction II 2.0 0.5 3.86 (1.89, 7.92)* Intensification I 1.6 0.7 2.33 (1.15, 4.77)* Intensification II 4.7 1.6 2.93 (1.44, 5.93)* 1adjusted for age, race, sex, and insurance status; *statistically significant Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Daunorubicin Dose Intensification for Induction Therapy in Acute Myeloid Leukemia Patients with FLT3-ITD Mutants

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4033-4033
Author(s):  
Eun-Ji Choi ◽  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Han-Seung Park ◽  
Sun-Hye Ko ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
High Dose ◽  
Dose Intensification ◽  
Acute Myeloid

Abstract Background Patients with FLT3-ITD mutated acute myeloid leukemia (AML) have generally poor survival. Recent update of ECOG trial comparing standard- vs. high-dose daunorubicin showed that daunorubicin dose intensification improved survival in AML with FLT3-ITD mutants (Blood 2016;127:1551). In subgroup analysis of our previous randomized trial, high-dose daunorubicin seemed to be more effective than idarubicin in AML patients with FLT3-ITD mutants (ASH abstract No. 2535, 2015). In this retrospective investigation, we aimed to evaluate the role of daunorubicin dose intensification for induction therapy in AML patients with FLT3-ITD mutants who were treated at a single institute. Methods We analyzed data from 120 patients of newly diagnosed FLT3-ITD mutated AML patients who received induction chemotherapy between January 2002 and March 2016. The regimens consisted of high-dose daunorubicin (HD-DN, 90 mg/m2/d x 3d, n=39), standard-dose daunorubicin (SD-DN, 45 mg/m2/d x 3d, n=48), or idarubicin (IDA, 12 mg/m2/d x 3d, n=33) in combination with cytarabine (200 mg/m2/d x 7d). Patients with acute promyelocytic leukemia were not included. Results After the first round of induction chemotherapy, 53 patients had persistent leukemia; 50 received the second round of induction chemotherapy consisting of daunorubicin (45 mg/m2/d x 2d) or idarubicin (8 mg/ m2/d x 2d) in addition to cytarabine (200 mg/m2/d x 5d) and 3 received other regimens. A total of 81 patients achieved CR, and the CR rates were 76.9%, 58.3%, and 69.7% in HD-DN, SD-DN, and IDA, respectively (P=0.175). The 4-year cumulative incidence of relapse (CIR) of these 81 patients was 48.8%. With the median follow-up duration of survivors of 59.9 months (range, 4.6-170.7), 4-year overall survival (OS) and event-free survival (EFS) were 57.1%/27.7%/35.7% (P=0.025) and 45.2%/23.9%/36.0% (P=0.042) in HD-DN, SD-DN, and IDA, respectively. HD-DN showed statistically higher OS (hazard ration [HR], 0.424; P=0.005) and EFS (HR, 0.497; P=0.01), and lower CIR (P=0.036) than SD-DN, while OS and EFS differences between HD-DN and IDA were not statistically significant. Conclusion Daunorubicin dose intensification for induction therapy seemed to be effective in AML patients with FLT3-ITD mutants. Further studies are needed to investigate whether HD-DN is superior to IDA in this population. Considering high relapse rate, combination strategies of daunorubicin dose intensification and targeted agents such as FLT3 inhibitors should be developed. Disclosures No relevant conflicts of interest to declare.

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