Anna B. Halpern

Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

Measurable (‘minimal’) residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRDneg/MRDneg patients had excellent outcomes, whereas both MRDneg/MRDpos patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRDpos patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia.

### Case 1 A 48-year-old man presents with epistaxis, fatigue, and pancytopenia, and is diagnosed with acute myeloid leukemia (AML) with a t(9;11)(p22;q23) translocation in 16 of 20 metaphases. He has an excellent performance status and no comorbidities. Curative-intent chemotherapy with cytarabine

Association of Risk Factors, Mortality, and Care Costs of Adults With Acute Myeloid Leukemia With Admission to the Intensive Care Unit

Importance Adults with acute myeloid leukemia (AML) commonly require support in the intensive care unit (ICU), but risk factors for admission to the ICU and adverse outcomes remain poorly defined. Objective To examine risk factors, mortality, length of stay, and cost associated with admission to the ICU for patients with AML. Design, Setting, and Participants This study extracted information from the University HealthSystem Consortium database on patients 18 years or older with AML who were hospitalized for any cause between January 1, 2004, and December 31, 2012. The University HealthSystem Consortium database contains demographic, clinical, and cost variables prospectively abstracted by certified coders from discharge summaries. Outcomes were analyzed using univariate and multivariable statistical techniques. Data analysis was performed from November 15, 2013, to August 15, 2016. Main Outcomes and Measures Primary outcomes were admission to the ICU and inpatient mortality among patients requiring ICU care. Secondary outcomes included length of stay in the ICU, total hospitalization length of stay, and cost. Results Of the 43 249 patients with AML (mean [SD] age, 59.5 [16.6] years; 23 939 men and 19 310 women), 11 277 (26.1%) were admitted to the ICU. On multivariable analysis (with results reported as odds ratios [95% CIs]), independent risk factors for admission to the ICU included age younger than 80 years (1.56 [1.42-1.70]), hospitalization in the South (1.81 [1.71-1.92]), hospitalization at a low- or medium-volume hospital (1.25 [1.19-1.31]), number of comorbidities (10.64 [8.89-12.62] for 5 vs none), sepsis (4.61 [4.34-4.89]), invasive fungal infection (1.24 [1.11-1.39]), and pneumonia (1.73 [1.63-1.82]). In-hospital mortality was higher for patients requiring ICU care (4857 of 11 277 [43.1%] vs 2959 of 31 972 [9.3%]). On multivariable analysis, independent risk factors for death in patients requiring ICU care included age 60 years or older (1.16 [1.06-1.26]), nonwhite race/ethnicity (1.18 [1.07-1.30]), hospitalization on the West coast (1.19 [1.06-1.34]), number of comorbidities (18.76 [13.7-25.67] for 5 vs none), sepsis (2.94 [2.70-3.21]), invasive fungal infection (1.20 [1.02-1.42]), and pneumonia (1.13 [1.04-1.24]). Mean costs of hospitalization were higher for patients requiring ICU care (

Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms

83 354 vs

A comparison of patients with acute myeloid leukemia and high-risk myelodysplastic syndrome treated on versus off study

41 973) and increased with each comorbidity, from

Impact of region of diagnosis, ethnicity, age, and gender on survival in acute myeloid leukemia (AML)

50 543 for patients with no comorbidities to

A Phase 1/2 Study of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults with Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

124 820 for those with 5 or more comorbidities. Conclusions and Relevance Admission to the ICU is associated with high mortality and cost that increase proportionally with the comorbidity burden in adults with AML. Several demographic factors and medical characteristics identify patients at risk for admission to the ICU and mortality and provide an opportunity for testing primary prevention strategies.

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

Outcomes with “7 + 3” are often unsatisfactory in acute myeloid leukemia (AML). Trials demonstrating improved outcomes with high-dose cytarabine, addition of cladribine, or escalated anthracycline doses prompted a phase 1/2 study (NCT02044796) of G-CSF, cladribine, high-dose cytarabine, and dose-escalated mitoxantrone (GCLAM) in adults with newly-diagnosed AML or other high-grade myeloid neoplasms. One hundred and twenty-one patients, median age 60 (range 21–81) years, were enrolled. In phase 1, cohorts of 6–12 patients were assigned to 12–18 mg/m2/day of mitoxantrone as part of GCLAM. Because all dose levels were well-tolerated, mitoxantrone at 18 mg/m2 was declared the recommended phase 2 dose (RP2D). 74/94 (79%) patients treated at the RP2D achieved a complete remission (CR; 67/74 without measureable residual disease [MRD]) for an overall MRDneg CR rate of 71% (primary phase 2 endpoint). Seven patients achieved a CR with incomplete blood count recovery (CRi; 7%, 5 MRDneg) for a CR/CRi rate of 81/94 (86%). Four-week mortality was 2%. After adjustment, the MRDneg CR and CR/CRi rates compared favorably to 100 matched controls treated with 7 + 3 at our center and 245 matched patients treated with 7 + 3 on a cooperative group trial. Our data indicate GCLAM with mitoxantrone at 18 mg/m2/day is safe and induces high-quality remissions in adults with newly-diagnosed AML.

Assessing Selection Bias in the Assignment to Investigational Acute Myeloid Leukemia (AML) Therapy

Abstract Patients with newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS, ≥10% blasts) often receive intensive chemotherapy at diagnosis and relapse. We retrospectively identified 365 patients and categorized the reasons for receiving treatment off study (medical, logistical, or unclear). The pretreatment characteristics of the on and off study groups were similar. Rates of the complete remission (CR) without measurable residual disease were significantly higher for ND patients treated on versus off study (61% versus 35%), but CR rates and survival were low for all RR patients regardless of study assignment. The subset of ND patients treated off study for medical reasons had significantly decreased overall survival and relapse-free survival. Standard, stringent study eligibility criteria may delineate a population of ND, but not RR, patients with improved outcomes with intensive induction chemotherapy.

A Comparison of Patients with Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome Treated On versus Off Study

Abstract Aim: Acute myeloid leukemia (AML) is an aggressive hematopoietic clonal disorder characterized by the increased blasts and poor survival outcome, which is mainly driven by cytogenetic and molecular abnormalities. Here, we investigated the prognostic impact of other demographic parameters on the survival outcomes in AML patients. Method: We reviewed the Surveillance, Epidemiology, and End Result (SEER) database to collect demographic information, including age, diagnosis, gender, race, and geographic region in patients with non-acute promyelocytic leukemia AML, between 2004–2008. The primary end-point of our study was 3-year overall survival (OS), which was estimated by the Kaplan–Meier method and Cox regression model. Results: A total of 13,282 patients were included in our analyses. Increasing age (HR 1.2, p < .0001), male gender (HR 1.05, p = .01), and geographic region of Midwest (HR 1.07, p = .002) were associated with inferior 3-year OS in univariate analysis, and these parameters remained independent prognostic factors in multivariate analyses. Conclusions: AML is a heterogeneous myeloid neoplasm with patient outcomes largely dictated by the cytogenetics and somatic mutations. In our study, additional demographic factors, including advanced age, male gender, and geographic region of AML diagnosis were associated with OS outcome in non-APL AML patients.