Complications in Acute Myeloid Leukemia Inductions Prior to Count Recovery: A Feasibility Study for Outpatient Care at an Academic Center

Introduction

Adults with newly diagnosed acute myeloid leukemia (AML) who receive intensive remission induction typically remain hospitalized until blood count recovery due to the high risk of infection and bleeding related to pancytopenia. This usually translates into at least 4 weeks of hospitalization, which can lead to reduced quality of life, increased risk of nosocomial infections, significant resource utilization and economic burden. Previous studies conducted at academic centers with large AML populations have suggested that outpatient management following induction chemotherapy is feasible and safe with close follow-up. These studies may have limited generalizability based on exceptional outpatient resources. Thus, this practice has not been widely adopted. To assess the feasibility of early patient discharge at our academic center which provides care for a smaller AML population, where we have a 6-days per week infusion center and hospitalize all AML patients undergoing induction until count recovery, we conducted a retrospective analysis of complications prior to blood count recovery in this patient population.

Methods

We identified patients ≥18 years with newly diagnosed non-APL AML admitted to the University of California, Davis Medical Center from 1/1/14 to 1/1/19 who received induction chemotherapy with cytarabine/daunorubicin (7+3) or a regimen of similar intensity with first interim bone marrow biopsy showing hypocellularity with <5% blasts. Endpoints included the rate of complete remission, infectious and hemorrhagic complications, transfusions, ICU transfers and death. We grouped timing of complications as those observed prior to and on or after day 15 of induction therapy until discharge. Patients who received a second induction regimen were censored at time of the start of the second regimen.

Results

Overall, 50 patients were identified; 42 (84%) received 7+3, 3 (6%) received FLAG and 5 (10%) received liposomal daunorubicin-cytarabine induction. Median age was 56 (range 25-81) years. ELN 2017 favorable, intermediate and adverse risk disease was observed in 18 (36%), 20 (40%) and 12 (24%) patients, respectively. Forty-nine (98%) patients with a negative interim marrow achieved a complete remission with first induction therapy. Forty-five (90%) patients had infectious complications at any time (Table 1), with 34 (68%) having infectious complications occurring prior to day 15 of induction. All patients with culture negative neutropenic fever prior to day 15 of induction as their only infectious complication had no further infectious complications throughout hospitalization although all received IV antibiotics until count recovery. Ten (20%) patients had hemorrhagic complications at any time (Table 1), with 9 (18%) having hemorrhagic complications occurring between day 15 of induction and discharge. Median platelet transfusion volume between days 15-21 and 22-discharge was 3.5 (range 1-18) and 0 (range 0-15) units, respectively. Three (6%) patients required ICU transfer. All ICU transfers occurred after day 14 of induction. One patient had hypoxic respiratory failure on admission and required transfer back to the ICU. Death prior to marrow recovery was observed in 1 patient (2%) due to subdural hemorrhage.

Conclusion

Intensive remission induction in hospitalized patients with newly diagnosed AML is associated with good efficacy and safety outcomes for patients with blast clearance on interim bone marrow biopsy. Although the rate of infectious complications was high, the majority debuted early during hospitalization and the rate of ICU transfers was low. All patients with culture negative neutropenic fever prior to day 15 of induction as their sole infectious complication who were treated with IV antibiotics had no further infectious complications throughout hospitalization. Hemorrhagic complications more commonly occurred later during hospitalization, although platelet transfusion requirements were manageable after day 15 of induction. These data suggest that at our institution, select patients receiving intensive remission induction and without infectious complications could be considered for early discharge and close outpatient follow-up after interim bone marrow biopsy showing hypoplasia. A prospective early discharge study to confirm these findings is being developed.