Comparison of Outcomes after Early Hospital Discharge (EHD) Following Intensive Induction Vs. Post-Remission Chemotherapy for Adults with Acute Myeloid Leukemia (AML) and Other High-Grade Myeloid Neoplasms
Authors: Halpern Anna B. , Howard Nicholas P , Othus Megan , Hendrie Paul C. , Baclig Nikita Vashi , Buckley Sarah A , Percival Mary-Elizabeth M. , Becker Pamela S. , Scott Bart L. , Oehler Vivian G. , Gernsheimer Terry B. , Keel Sioban B. , Orozco Johnnie , Cassaday Ryan D. , Shustov Andrei R , Hartley Garrett , Welch Verna L , Estey Elihu H. , Walter Roland B. 
Published: November 2019

Background: An international survey we recently conducted indicated that, even today, adults with acute myeloid leukemia (AML) standardly remain hospitalized after completion of induction chemotherapy until resolution of cytopenias due to a high risk of infection and frequent need for transfusions. In contrast, over the last five years at our institution, hospital discharge immediately following completion of induction chemotherapy has become routine after a phase 2 trial evaluating an Early Hospital Discharge (EHD) strategy showed this approach to be safe and cost-effective. On the other hand, EHD is a nearly-universal practice following post-remission or "consolidation" therapy. Here, we sought to compare safety and healthcare resource utilization outcomes for patients who are discharged to the outpatient setting following intensive induction vs. consolidation chemotherapy.
Methods: We retrospectively identified all adults aged ≥18 years with newly-diagnosed AML/high-grade myeloid neoplasms (≥10% blasts in peripheral blood/ bone marrow) who started AML-like intensive induction or consolidation chemotherapy ("7+3," high-dose cytarabine [HiDAC], or a regimen of similar/higher intensity) at our institution from 8/1/14 (completion of our phase 2 EHD study) to 7/31/18. EHD was defined as discharge from the hospital within 72 hours of completing chemotherapy (as done in our phase 2 study). Induction therapy was defined as the first course of intensive chemotherapy for untreated disease. Consolidation therapy was defined as intensive therapy if the marrow (and hematologic parameters) prior to starting treatment showed complete remission by standard International Working Group criteria. Patients with relapsed or primary refractory disease were excluded from this analysis. The study period began on the day of initial discharge and ended with count recovery, death, receipt of additional disease-directed therapy, transfer of care, or once 42 days elapsed. We collected baseline demographic and clinical characteristics, logistical information, and treatment regimen. Outcomes of interest including readmission timing/reasons, intensive care unit (ICU) admission, resource utilization (number of lab visits, provider visits, days of IV antimicrobial use, units of transfused red blood cell [RBC] and platelets) and survival. All analyses accounted for correlation between patients because 100 patients were in both the induction and consolidation datasets and 62 patients had more than 1 consolidation cycle in the dataset.
Results: We identified 215 induction cycles and 225 consolidation cycles that met our criteria for EHD. As detailed in Table 1, induction EHD patients had worse baseline performance status and higher white blood cell counts than consolidation EHD patients. Consolidation patients spent more time on study (27.8 vs. 24.7 days) and spent a higher proportion of their study time as outpatients (mean of 79% vs. 71% of study time; p&lt;0.001), at least in part because of a lower readmission rate (mean of 0.8 vs. 1.1 readmissions; p&lt;0.001). There were no differences in the proportion of study days spent in the ICU (1.6% after induction vs 0.6% after consolidation; p=0.27). However, the early death rate (within 30 days of study day 1) was higher in the induction EHD group (4% vs. 1%; p=0.03). A higher proportion of study days were spent on IV antimicrobials in the induction group (37% vs. 32% days; p=0.06), and though absolute numbers were small, the induction cohort had more frequent physician (0.07 vs. 0.05; p&lt;0.001) and nurse/advanced practiced practitioner visits (0.09 vs. 0.08; p=0.02) per study day than the consolidation group, respectively. There were no differences in mean lab visits per outpatient study day (p=0.63), in mean number of red blood cell transfusions per study day (p=0.18) or mean number of platelet transfusions per study day (p=0.51).
Conclusion: Although the early death rate, as would be expected given a baseline sicker population, was higher for EHD patients following induction compared to consolidation chemotherapy, there were no differences between the two groups in requirements for ICU care, laboratory monitoring, or transfusion need in the outpatient setting. This suggests that an EHD strategy following induction therapy may be safely and reasonably implemented at centers with infrastructure supporting EHD following standard consolidation therapy.

Disclosures
Halpern: Pfizer Pharmaceuticals: Research Funding; Bayer Pharmaceuticals: Research Funding. Othus:Glycomimetics: Other: Data Safety and Monitoring Committee; Celgene: Other: Data Safety and Monitoring Committee. Buckley:CTI BioPharma: Employment, Equity Ownership. Percival:Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Becker:The France Foundation: Honoraria; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; Accordant Health Services/Caremark: Consultancy. Scott:Novartis: Consultancy; Agios: Consultancy; Incyte: Consultancy; Celgene: Consultancy. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy; NCCN: Consultancy. Gernsheimer:Fuji film: Consultancy; Bioverativ: Consultancy; Dova pharmaceuticals: Consultancy; Novartis: Honoraria; Cellphire: Consultancy; Amgen: Consultancy, Honoraria; Rigel: Consultancy; Shionogi: Consultancy. Orozco:Actinium Pharmaceuticals: Research Funding. Cassaday:Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests. Shustov:Seattle Genetics, Inc.: Research Funding. Hartley:Pfizer Inc.: Employment, Equity Ownership. Welch:Pfizer Inc: Employment, Equity Ownership. Walter:Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding.