High Risk AML Outpatient Management: A Retrospective Analysis of Bacteremia Incidence Following Chemotherapy.
Authors: Halim Timotheus Y. , Lavoie Julye C. , Barnett Michael J. , Nantel Stephen H. , Nevill Thomas J. , Shepherd John D. , Sutherland Heather J. , Hogge Donna E. , Song Kevin W. , Forrest Donna L. , Toze Cynthia L. , Smith Clay A. 
Published: October 2019

Treatment of acute myeloid leukemia (AML) involves aggressive remission inducing (IND) chemotherapy, and consolidation (CON) chemotherapy aimed at preventing or delaying relapse. Since September 2001, our institution has implemented a selective discharge protocol, which allows the majority of CON cycles, and some selected IND cycles, to be administered entirely on outpatient (OP), or early discharge (ED: prior to ANC >0.5 x 109/L or before d+15) basis. One of the primary concerns associated with this novel practice is the prompt management of infections in these high-risk neutropenic patients, requiring immediate administration of empirical broad spectrum parenteral antibiotics. Our group previously reported the safety and feasibility of OP management (Savoie Blood 2002, 100:11 p766a). We now present a comparative review of the incidence of septicemia over a 5 year period, encompassing the change in management policy. We investigated the impact of selective discharge on infectious morbidity, and the spectrum of bacterial pathogens and their resistance profile.

OP received all standard chemotherapy and supportive care in outpatient settings. Supportive care was modified for OP, adding Ciprofloxacin 500mg po BID as antimicrobial prophylaxis d+1 from the start of chemotherapy. Universal supportive care for all pts consisted of Acyclovir 600mg po qid or Valacyclovir 500mg po od (if HSV IgG positive) and Fluconazole 200–400mg po od or Itraconazole 200mg po bid (if previously aspergillus infection). The prophylaxis was stopped upon ANC recovery. Pts were not routinely treated with G-CSF.

Between Feb 1999 and Feb 2004, 328 IND and 295 CON cycles of chemotherapy (total=623) were given to 295 patients. Following guidelines adopted in Sep 1, 2001 the majority of CON cycles [84% (133/159)] were administered to pts in our OP day-care clinic, also a smaller number of CON and some IND cycles were candidates for ED. Analysis of trends indicated a minor decrease in overall bacteremia incidence following the implementation of OP protocol. [21% (65/303) before 1-Sept-01, 19% (61/320) after 1-Sept-01),NS]. However, a significant decrease in bacteremia was observed in the CON cycle subgroup (which included the largest OP population), from 31% (42/136) before, to 19% (29/159) after 1-Sept-01 (p=0.01). In addition, a notable shift in incidence of gram-ve bacteremia occurred in IP (-cipro prophylaxis) compared to OP (+cipro prophylaxis) from 49% to 27% of total bacterial infections. Nevertheless, a larger fraction of gram-ve isolates from OP exhibited resistance to ciprofloxacin. No treatment related deaths occurred as a result of infection in the OP population.

This report constitutes the first comparative study of bacteremial complications in high risk neutropenic AML patients treated in OP settings. OP management in conjunction with prophylactic antibiotherapy is safe, and results in a significant decrease in bacteremia. However, the use of gram-ve coverage prophylaxis introduced a shift in pathogenic microorganisms and emergence of resistance. Supported by our findings we propose that selective OP management of AML pts should be encouraged, keeping in mind the change in the spectrum of infections.