Background and Aim

Acute myeloid leukemia (AML) at diagnosis can be an emergency. Induction mortality reaches 5 to 15% for patients under 60 years of age, and 15 to 30% for subjects over 60. 10 to 34% of patients will require a shift to intensive care unit (ICU) during induction and most of organ failures occur in the first few days.

To optimize and improve the initial management of AML, we selected patients with high risk of induction mortality based on white blood cell count (WBC) ≥ 50 G/l and thrombocytopenia ≤ 50G/l at diagnosis. These patients were systematically admitted into ICU even without organ failure.

Patients and Methods

Our study was conducted in two hospitals, between 1st January 2000 and 31thDecember 2010. We included patients with newly diagnosed AML, aged 18 to 75 years, with both WBC ≥ 50G/l and platelets ≤ 50G/l, and no organ failure (group 1). 41 patients transferred to ICU based on conventional criteria (organ failure) during this period were not included in the study. Patients were directly admitted in ICU for diagnosis and treatment of AML(induction chemotherapy), and were jointly managed by both the intensivist and the hematologist. Patients were discharged from ICU without any non-hematological organ failure. Results were compared to a control group of similar patients admitted in another university hospital were high-risk patients are managed conventionnaly (ie no systematic ICU transfer in the absence of organ failure) (group 2). We defined organ failure by the requirement of mechanical ventilation for respiratory deficiency, renal remplacement therapy for renal failure, vaso-active drugs for hemodynamic and heart failure and when glasgow score was<7 for neurological failure.

Results

130 patients were included, 50 patients in group 1 and 79 patients in group 2. Neither age at diagnosis and AML characteristics differed significantly between the two groups, nor complete remission rate(80% versus 70,5%) and relapse rate(55% versus 49%). 18 patients (36%) presented organ failure in group 1, 9 (11%) in group 2. The median time between induction and organ failure was 1 day(1-6) in group 1 and 3 days (1-24) in group 2. The main organ failure was acute respiratory failure, with 10 patients (56%) who needed invasive mechanical ventilation in group 1 and 8 (89%) in group 2. In group 1, renal replacement therapy and vaso-active drugs was used in 4 (22%) and 6 (33%) patients, respectively, versus 3 (33%) and 7 patients (78%), respectively, in group 2. The median length of stay in ICU was 5 days in patients without organ failure in group 1 (2-18), 11,5 days in patients with organ failure in group 1 (4-45), and 6 days in group 2 (1-37). Overall survival was not significantly different between the two groups (p 0.28). Six patients (12%) died in the group 1 at day 30 of induction chemotherapy, 14 patients (18%) in the group 2. Concerning patients who developed organ failure, the 30 days survival was significantly better in patients already monitored in ICU (group 1), 67 %, versus 22% in group 2 (p=0.02). The overall survival of patients of group 1 who had presented organ failure but alive after their ICU stay, was not statistically different compared to patients of group 1 without organ failure during induction (median 8 months versus 16 months, p 0,09).

Conclusion

There were more critical patients in the study group, but their 30 days survival was significantly better than in patients with organ failure in the control group. However, overall survival of the two groups was comparable. This study highlights a new strategy to improve initial management of AML. The rapid onset of complications (<3 days in more than 90%) allows considering short stays in ICU for patients who will not presented organ failure in the first 3 days of induction. The main limiting factor for this management is its applicability. These results have to be confirmed by a multicentric comparative study.

Table 1
Study group
n=50
Control group
n=79
p-value
Median age at diagnosis (years) 53,5 (16-75) 56 (24-75) 0,50 
Sex (M/F) 27/23 45/34 0,74 
Initial WBC count (median, G/l) 121 116 0,15 
Initial platelets count (median, G/l) 29 32 0,72 
Organ failure :
n (%)
Time between induction and organ failure (median, in days) 
-
18 (36%)
1 (1-6) 
-
9 (11%)
3 (1-25) 
-
<0,01
0,23 
Type of organ failure :
Respiratory
Renal
Heart and hemodynamic
Neurologic 
-
10/18 (56%)
4/18 (22%)
6/18 (33%)
1/18 (6%) 
-
8/9 (89%)
3/9 (33%)
7/9 (78%)
1/9 (11%) 
-
0,19
0,88
0,08
0,80 
Death in ICU 6/18 (33%) 8/9 (89%) 0,02 
Study group
n=50
Control group
n=79
p-value
Median age at diagnosis (years) 53,5 (16-75) 56 (24-75) 0,50 
Sex (M/F) 27/23 45/34 0,74 
Initial WBC count (median, G/l) 121 116 0,15 
Initial platelets count (median, G/l) 29 32 0,72 
Organ failure :
n (%)
Time between induction and organ failure (median, in days) 
-
18 (36%)
1 (1-6) 
-
9 (11%)
3 (1-25) 
-
<0,01
0,23 
Type of organ failure :
Respiratory
Renal
Heart and hemodynamic
Neurologic 
-
10/18 (56%)
4/18 (22%)
6/18 (33%)
1/18 (6%) 
-
8/9 (89%)
3/9 (33%)
7/9 (78%)
1/9 (11%) 
-
0,19
0,88
0,08
0,80 
Death in ICU 6/18 (33%) 8/9 (89%) 0,02 
Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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