General AML

Effect of linezolid on hematologic recovery in newly diagnosed Acute Myeloid Leukemia patients following induction chemotherapy

In Europe, linezolid is indicated in adults for the treatment of community acquired pneumonia and nosocomial pneumonia when known or suspected to be caused by susceptible Gram positive bacteria.  A.N. Nedved et al. investigated the potential benefits of linezolid on hematologic outcomes in 225 newly diagnosed AML patients following induction chemotherapy. The results were published in Pharmacotherapy in August 2016.

Key results
  • The primary endpoint of time to neutrophil recovery was not statistically different (28 days (LZD group) vs. 26 days (control group); P=0.675).
  • Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs. 16 days; P<0.001).

In summary, these results are promising but are preliminary. Further investigations are needed to define the long-term safety and tolerability profile of linezolid in patients with newly diagnosed AML.

Abstract
OBJECTIVE:

Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy.

DESIGN:

Single-center, retrospective, observational, cohort study.

SETTING:

Large, tertiary care academic medical center.

PATIENTS:

225 patients ≥18 years admitted between December 2010-2013 with newly diagnosed AML were assessed for inclusion. Patients were identified via ICD9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid + gram-negative antimicrobial, N=21) or control group (vancomycin or daptomycin + gram-negative antimicrobial, N=47).

INTERVENTIONS:

LZD group received linezolid ≥72 hours. Control group received vancomycin or daptomycin ≥72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥72 hours of linezolid.

MEASUREMENTS/RESULTS:

The primary endpoint of time to neutrophil recovery was not statistically different (28 days (LZD group) vs. 26 days (control group); P=0.675). The pre-planned subgroup analysis of patients who received ≥14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days (LZD group) vs. 26 days (control group); P=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs. 16 days; P<0.001). Secondary endpoints not found to be statistically significant included: platelet count at time of neutrophil recovery, duration of neutropenia, and length of hospital stay.

CONCLUSIONS:

There were no significant differences in hematologic outcomes in newly diagnosed AML patients who received linezolid for extended gram positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia. 

References
  1. Nedved A.N. et al. Effect of linezolid on hematologic recovery in newly diagnosed acute myeloid leukemia patients following induction chemotherapy. Pharmacotherapy. 2016 Aug 13. DOI: 10.1002/phar.1824. [Epub ahead of print].