ORIGINAL ARTICLE: CLINICAL

Outcome and prognostic factors of patients with acute leukemiaadmitted to the intensive care unit for septic shock

HYE YUN PARK1, GEE YOUNG SUH1, KYEONGMAN JEON1, WON-JUNG KOH1,

MAN PYO CHUNG1, HOJOONG KIM1, O JUNG KWON1, KIHYUN KIM2,

JUN HO JANG2, CHUL WON JUNG2, EUNHAE KANG3, & MIN-JI KIM4

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan

University School of Medicine, Seoul, Korea, Republic of Korea, 2Division of Hematology-Oncology, Department of Medicine,

Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of Korea, 3Division of

Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea,

Republic of Korea, and 4Biostatistics Unit, Samsung Biomedical Research Institute, Seoul, Korea, Republic of Korea

(Received 3 April 2008; revised 14 July 2008; accepted 16 July 2008)

AbstractThe purpose of the present study was to evaluate outcomes and identify prognostic factors in patients with acute leukemia whowere admitted to the intensive care unit (ICU) with septic shock. Medical records of 50 patients with acute leukemia who weretreated for septic shock in the Medical ICU of Samsung Medical Centre between September 2001 and June 2006 wereretrospectively reviewed. The data were analysed for patient outcomes and for predictors of ICU mortality. ICU mortality and in-hospital mortality were 60% and 68%, respectively. The need for mechanical ventilation (p5 0.001), the addition of nor-epinephrine todopamine(p5 0.001)andapoorSequentialOrganFailureAssessment (SOFA)score (p50.001)wereassociatedwith ICU mortality in the univariate analysis. In the multivariate analysis using the Cox-model, a relapsed/refractory status forleukemia and poor SOFA score were independent predictors for ICU mortality. In conclusion, although the mortality was high inpatients with acute leukemia who were admitted to the ICU for septic shock management, it was not high enough to precludeintensive care. Patients with severe organ failure and a relapse/refractory status for leukemia had a significantly worse prognosis.

Keywords: Acute leukemia, intensive care unit, septic shock

Introduction

Adult patients with acute leukemia have a high

incidence of relapse, and only 20–30% achieves long-

term disease-free survival [1,2]. To prolong survival,

aggressive therapy is necessary but often culminates

in serious complications that require intensive care.

The outcome for critically ill patients with hemato-

logic malignancies is grave, although the mortality

rate has decreased over the last decade [3]. The

prognosis is especially poor in patients who require

mechanical ventilation and patients with septic shock

[4–6]. Only a limited number of available studies

have specifically evaluated acute leukemia patients

with septic shock [7]. Thus, the present study was

undertaken to evaluate outcomes and identify prog-

nostic factors in patients with acute leukemia who

were admitted to the intensive care unit (ICU) for

septic shock management.

Patients and methods

This study was approved by the Institutional Review

Board of Samsung Medical Centre, and the require-

ment for patient consent was waived given the

retrospective nature of the study. Samsung Medical

Centre is a 1250-bed tertiary referral centre in Seoul,

South Korea. Its 10-bed Medical Intensive Care Unit

(MICU) treats approximately 420 patients per year.

Between September 2001 and June 2006, 113 acute

Correspondence: Gee Young Suh, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Centre, Sungkyunkwan

University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. Tel: þ82-2-3410-3429. Fax: þ82-2-3410-6956. E-mail: suhgy@skku.edu

Leukemia & Lymphoma, October 2008; 49(10): 1929–1934

ISSN 1042-8194 print/ISSN 1029-2403 online � 2008 Informa Healthcare USA, Inc.

DOI: 10.1080/10428190802353609

Leu

k L

ymph

oma

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

ity o

f C

alif

orni

a Ir

vine

on

11/0

3/14

For

pers

onal

use

onl

y.

leukemia patients were admitted to the MICU. Of

those patients, 50 patients who had septic shock at

admission were included in the present study, and

their medical records were reviewed retrospectively.

Septic shock was defined as acute circulatory failure,

unexplainable by other causes, in patients with

severe sepsis and acute circulatory failure was defined

as persistent arterial hypotension (systolic arterial

pressure, 590 mmHg; mean arterial pressure,

560 mmHg; or a reduction in systolic arterial

pressure of 440 mmHg from baseline), despite

adequate volume resuscitation [8]. At our institution,

patients undergoing anti-leukemic chemotherapy do

not receive routine anti-bacterial or anti-fungal

prophylaxis. Patients undergoing hematopoietic

stem cell transplantation (HSCT) receive prophylac-

tic sulphamethoxazole/trimethoprim and acyclovir

until engraftment, but no antifungal prophylaxis is

given. When patients develop neutropenic fever, they

are treated with empirical antibiotics and/or anti-

fungal agents according to the Infectious Diseases

Society of America (IDSA) guideline [9]. When

patients had more than one ICU admission during

the same hospitalisation period, data from only the

first ICU admission were analysed.

Information collected at admission to the ICU

included age, gender, acute leukemia type, cytogen-

tics [acute myeloid leukemia (AML), as defined by

Southwest Oncology Group (SWOG); acute lym-

phoblastic leukemia (ALL), the presence of the

Philadelphia chromosome], leukemia status (in

remission, newly diagnosed, or relapsed/refractory),

treatment received (high-dose chemotherapy and/or

HSCT), infection site, presence of oliguria (24-h

urinary output, 5500 mL), presence of adrenal

insufficiency and laboratory data such as neutrophil

count, levels of urea, creatinine, total bilirubin,

lactate, prothrombin time and the PaO2/FiO2 ratio.

Patients in whom leukemia had relapsed following

intensive front-line chemotherapy or who had re-

ceived re-induction therapy after a failed response to

initial induction therapy were considered to have a

relapsed/refractory status. Patients who had received

myeloablative therapy for HSCT within 4 weeks of

ICU admission were considered to have received

high-dose chemotherapy. Severe neutropenia was

defined as a neutrophil count below 0.56 109/L.

Acute Physiology and Chronic Health Evaluation

(APACHE) II score, Simplified Acute Physiology

Scale (SAPS) II score and Sequential Organ Failure

Assessment (SOFA) score were calculated to assess

the disease severity. APACHE II score and SAPS II

score were calculated using the worst value for that

variable during the first 24 h of ICU admission and

SOFA scores were calculated from the data at

admission [10–12]. The following conditions were

evaluated during the ICU stay: the need for

mechanical ventilation, continuous renal replace-

ment therapy (CRRT), addition of norepinephrine

to dopamine as vasopressor therapy, appropriate

antibiotics or steroids, the presence of microorgan-

isms in the bloodstream or fungal infection, the

duration of ventilation and the length of stay in the

ICU and in the hospital. Fungal infection was

defined as a growth of fungus from clinical specimen

and the initiation of treatment for that organism.

The data were analysed to identify factors related

to ICU mortality. The 1-year mortality rate was

also examined using medical records or telephone

interviews.

Statistical analysis

Statistical analysis was performed using the unpaired

Student’s t-test or the Mann–Whitney U test for

continuous variables and the chi-squared or the

Fisher’s exact test for categorical values, as appro-

priate. Multivariate analysis was conducted using the

Cox proportional hazards regression model with

forward selection, to determine independent pre-

dictive factors for mortality. Variables with a p value

less than 0.25 in the univariate analysis excluding

those used for calculating SOFA score were entered

into the model. Among the severity scores, SOFA

score was selected whereas APACHE II and SAPS II

were left out because we wanted to assess the impact

of severity of organ dysfunction/failure itself on

mortality and all the variables for SOFA score

overlapped with the other two scores. The variables

analysed were age, gender, the need for mechanical

ventilation, the presence of severe neutropenia, the

subtype of acute leukemia, the need for CRRT, the

relapse/refractory status and SOFA score. The good-

ness-of-fit was evaluated with the Hosmer and

Lemeshow test. Survival curves were calculated using

the Kaplan-Meier method, and statistical significance

was interpreted using the log-rank test. Values are

expressed as median and interquartile range. The p-

values were two-sided, with p5 0.05 considered to

be statistically significant. The Cox proportional

hazards regression model was executed with SAS

version 9.1 (SAS Institute, Cary, NC) and the

remaining analyses were performed using SPSS

14.0 (Chicago, IL, USA).

Results

Baseline clinical characteristics

The baseline clinical characteristics of the patients

are listed in Table I. There were 30 male and 20

female patients. The median age was 50 years

1930 H. Y. Park et al.

Leu

k L

ymph

oma

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

ity o

f C

alif

orni

a Ir

vine

on

11/0

3/14

For

pers

onal

use

onl

y.

(interquartile range, 35–62 years). Among the 50

acute leukemia patients admitted to the MICU of

Samsung Medical Centre for management of septic

shock, 35 had AML, 13 had acute lymphoid leukemia

and two had acute biphenotypic leukemia. Twenty-

two of 35 (63%) AML patients had intermediate- or

unfavorable-risk karyotypes and 4 of 13 (31%) ALL

patients had the Philadelphia chromosome. At the

time of admission to the ICU, a relapsed/refractory

status was present in 19 (17 relapsed, 2 refractory,

respectively). Pneumonia was the most common

underlying cause of septic shock (26 patients, 52%),

followed by catheter-related infections and infections

of gastrointestinal tract origin. Forty of 50 patients had

documented infections as evidenced by the growth of

organisms from relevant cultures or pathological

confirmation of a clinically relevant specimen. The

causative organisms were Gram-negative bacteria

(53%), Gram-positive bacteria (16%), fungal organ-

isms (18%) and polymicrobial organisms (13%).

Thirty patients had causative organisms identified

from blood samples. The median APACHE II, SAPS

II and SOFA scores at admission were 26 (22–32), 60

(52–71) and 13 (3–15), respectively. At admission, 38

patients (76%) had severe neutropenia and 7 (14%)

had received high-dose chemotherapy, and 14 (28%)

had received HSCT. Among 14 patients with HSCT

history, seven patients had allogeneic BMT and six

had autologous or allogeneic peripheral blood stem

cell transplantation. The remaining one patient

received cord blood transplantation.

The outcome and prognostic factors of ICU mortality

The ICU mortality rate was 60%, and the median

duration of stay in the ICU was 6 days (3–14 days). By

univariate analysis, there was no significant difference

in age, gender, subtype of acute leukemia, history of

HSCT, presence of severe neutropenia or relapsed/

refractory status between survivors and non-

survivors. At admission, the APACHE II

(p5 0.001), SAPS II (p¼ 0.004) and SOFA scores

(p5 0.001) of the survivors were significantly lower

than those of the non-survivors, and 90% of patients

with oliguria on admission died. Other factors

associated with mortality were the need for mechan-

ical ventilation (survivors vs. non-survivors: 25.6% vs.

74.4%; p5 0.001) and the requirement of norepi-

nephrine in addition to dopamine as vasopressor

therapy (survivors vs. non-survivors: 22.2% vs.

77.8%; p5 0.001). Among laboratory study results

at admission, the urea level (p¼ 0.023), total bilirubin

level (p¼ 0.005) and prothrombin time (INR)

(p¼ 0.011) showed significant differences between

the survivors and non-survivors (Tables II and III).

Multivariate analysis using the Cox model with

forward selection was performed to identify inde-

pendent variables associated with ICU mortality.

The relapsed/refractory status of the underlying

leukemia [Hazard Ratio (HR), 2.46; 95% CI, 1.11–

5.42)] and the SOFA score (HR, 1.25; 95% CI,

1.05–1.48) were the two independent variables

associated with mortality (Table IV).

One-year survival

The 1-year survival rate was 30% (15/50). Figure 1

shows the 1-year survival of acute leukemia patients

Table I. Baseline characteristics of patients on admission to the

ICU (n¼50)*.

Patients

No. Percentage

Demographics

Age, yr 50 (35–62)

Gender, male/female 30/20 60/40

Subtype of acute leukemia

AML (M1,M2, M3, M4,

M5, M6, others)

35 (2,9,2,7,7,2,7)

ALL (pre-B-cell,T-cell) 13 (11,2)

ABL 2

Cytogenetics

AML

Favorable/intermediate/

unfavorable

12/16/6 34/46/17

Unknown 1 3

ALL

The presence of

Philadelphia

chromosome

4 31

Major reasons for septic shock

Pneumonia 26/50 52

Catheter-related infection 7/50 14

Gastro-intestinal origin 6/50 12

Urinary tract infection 2/50 4

Necrotising fascitis 2/50 4

Unknown 7/50 14

Severity of illness

APACHE II score 26 (22–32)

SAPS II score 60 (52–71)

SOFA score 13 (3–15)

Therapy-related characteristics

Severe neutropenia at ICU

admission

38/50 76

Recent high-dose therapy 7/50 14

HSCT 14/50 28

530 days 2/14 14

30–90 days 1/14 7

490 days 11/14 79

*AML, acute myelogenous leukemia; ALL, acute lymphoblastic

leukemia; APACHE, acute physiology and chronic health evalua-

tion; SAPS, simplified acute physiologic score; SOFA, sequential

organ failure assessment; HSCT, hematopoietic stem cell trans-

plantation.

Values are expressed as median (interquartile range) or frequen-

cies (%).

Acute leukemia patients with septic shock 1931

Leu

k L

ymph

oma

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

ity o

f C

alif

orni

a Ir

vine

on

11/0

3/14

For

pers

onal

use

onl

y.

admitted to the ICU for septic shock management

stratified according to leukemia status. Patients with

a relapsed/refractory status had significantly worse

survival when compared with patients who were

either in remission or newly diagnosed (p¼ 0.009).

Only two of the 19 patients with a relapsed/refractory

status survived 1 year, and they died after 412 and

560 days, respectively.

Discussion

The aim of the present study was to evaluate

outcomes and identify prognostic factors in patients

with acute leukemia who were admitted to the ICU

for septic shock management. In these patients, the

ICU mortality was 60%, and the main predictive

factors for poor survival were the underlying disease

status and the severity of organ dysfunction.

In the present-day ICU, the intensivist is often

faced with difficult decisions on whether to allocate

limited resources to patients with grave prognosis

such as leukemia with septic shock. Well-defined

factors associated with prognosis can help the

clinician make these difficult decisions which often

involve discussions with patients and their families.

The ICU mortality rate for leukemia patients

requiring intensive care was higher in the present

study (60%) compared with those reported in

previous studies (42–53%) [3,5,13,14]. The major

reason for this difference is that the present study

included only patients with septic shock, which itself

is a poor prognostic factor in patients with hemato-

logic malignancy needing ICU care [15,16]. The

hospital mortality rate in the present study was 68%.

Of the 20 patients who were discharged from the

ICU after recovery from septic shock, four died

during the same hospital admission, owing to newly

developed infections. Two of these patients received

aggressive care including chemotherapy, and the

others were treated with palliative care. Higher

mortality rate was coincident with higher SAPS II

scores in our study (median score, 64) than those

reported in previous studies (scores in the mid-50s)

[5,13]. Our report and a study recently published by

Thakker et al. show that denying admission to a

patient purely based on leukemia diagnosis is

unreasonable. Forty percent of patients in the present

Table II. Categorical variables associated with ICU mortality in

acute leukemia patients with septic shock*.

Variables

Survived

(n¼ 20)

Died

(n¼ 30)

p valuen (%) N (%)

Factors at admission

Gender (male) 10 (33.3) 20 (66.7) 0.24

AML 12 (34.3) 23 (65.7) 0.21

Relapsed/refractory status 5 (26.3) 14 (73.7) 0.12

Recent high-dose therapy 2 (28.6) 5 (71.4) 0.51

History of HSCT 5 (35.7) 9 (64.3) 0.70

Severe neutropenia at

admission

13 (34.2) 25 (65.8) 0.18

Source 0.07

Unknown 0 (0.0) 7 (100)

Pneumonia 11 (42.3) 15 (57.5)

Catheter related infection 4 (57.1) 3 (42.9)

Gastro-intestinal infection 3 (50.0) 3 (50.0)

Urinary tract infection 2 (100) 0 (0.0)

Necrotising fascitis 0 (0.0) 2 (100)

Oliguria 1 (10.0) 9 (90.0) 0.04

Adrenal insufficiency (n¼ 22) 0.62

Yes 4 (36.4) 7 (63.6)

Relative 2 (66.7) 1 (33.1)

No 3 (37.5) 5 (62.5)

Factors during admission

Need for mechanical

ventilation

10 (25.6) 29 (74.4) 50.001

Renal replacement therapy 6 (27.3) 16 (72.7) 0.10

Use of norepinephrine 8 (22.2) 28 (77.8) 50.001

Use of steroid 9 (34.6) 17 (65.4) 0.49

Microorganism in the

blood (þ)

13 (43.3) 17 (56.7) 0.56

Fungal infection 5 (55.6) 4 (44.4) 0.45

*AML, acute myelogenous leukemia; HSCT, hematopoietic stem

cell transplantation.

Values are expressed as frequencies (%).

Table III. Univariate analysis of the continuous variables

associated with the ICU mortality in acute leukemia patients with

septic shock*.

Variables

Lived

(n¼20)

Died

(n¼ 30) p value

Age 53 (39–62) 50 (35–64) 0.863

Duration of

hospitalization

(days)

45 (38–69) 33 (23–56) 0.128

APACHE II

score

22 (20–25) 31 (25–34) 50.001

SAPS II score 54 (48–60) 64 (58–72) 0.005

SOFA score 11 (10–13) 13 (12–16) 50.001

Duration of

mechanical

ventilation

(days)

15 (6–18) 4 (3–14) 0.468

Laboratory data

Lactic acid

(n¼ 21)

2.3 (0.8–4.9) 3.6 (2.1–8.6) 0.277

PaO2/FiO2 139.3

(112.8–203.0)

101.6

(80.9–204.1)

0.074

Urea 15.6 (9.0–24.8) 21.9 (15.7–43.8) 0.023

Creatinine 0.8 (0.7–1.2) 1.2 (0.9–2.6) 0.272

Bilirubin 1.6 (0.7–2.7) 2.9 (1.6–8.0) 0.005

Prothrombin

time (INR)

1.4 (1.3–1.6) 1.6 (1.3–2.1) 0.011

*APACHE, acute physiology and chronic health evaluation;

SAPS, simplified acute physiologic score; SOFA, sequential organ

failure assessment; INR, international normalized ratio.

Values are expressed as median (interquartile range).

1932 H. Y. Park et al.

Leu

k L

ymph

oma

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

ity o

f C

alif

orni

a Ir

vine

on

11/0

3/14

For

pers

onal

use

onl

y.

study and 32% of patients in the study by Thakker

et al. survived ICU care [17]. One-year survival was

30% and 15%, respectively.

The two important prognostic factors associated

with ICU mortality and in-hospital mortality (data

not shown) was SOFA score and the status of acute

leukemia. It is not surprising that the SOFA score

was an independent predictor of mortality, as the

prognosis of cancer patients admitted to ICU for a

medical problem is related to the acute physiological

changes induced by complications of treatment

[7,18]. SOFA score is well documented as an

effective method for assessing the degree of organ

dysfunction in septic shock and is cited as a

prognostic factor for predicting outcome in a variety

of critically ill patients [7,19]. The higher the degree

of organ dysfunction, the less likely it is that the

patient will be able to withstand this life-threatening

insult and recover to a healthy state. This finding is

compatible with recent reports that SAPS II [20] and

APACHE II [17] can predict worse outcome in acute

leukemia patients admitted to the ICU.

None of the patients with an initial SOFA score of

16 or higher survived; both specificity and positive

predictive value for mortality being 100%. Sensitivity

and negative predictive value with a cut-off point of 16

were 27% and 48%, respectively. Similar cut-off points

for SAPS II (83) and APACHE II (39) had sensitivity

and negative predictive value of 17% and 44% and

13% and 43%, respectively. Thus, SOFA score was at

least as good as the other two scores in predicting grave

outcome, although being much easier to calculate

(uses six readily available variables at admission).

The value of this cut-off point should be evaluated

prospectively in a different patient population.

The status of the underlying malignancy was ano-

ther important factor in determining the outcome in

our patients. Patients with relapsed or refractory

leukemia have been shown to have a low complete

remission rate after chemotherapy, a high treatment-

related mortality and a low likelihood of prolonged

disease-free survival [21]. This trend held true in the

present study for the relapsed/refractory leukemia

patients with septic shock, as they showed a higher

mortality rate and significantly shorter survival time

when compared with the patients who were under-

going chemotherapy for the first time or were in

remission.

In a recently published study by Thakker et al. [17],

which evaluated prognostic factors for acute leukemia

patients admitted to the ICU, high APACHE II score,

use of pressors, undergoing bone marrow transplan-

tation preparative regimen and adverse cytogenetics

predicted worse outcome, although underlying dis-

ease state, type of leukemia and age did not. The

results are similar to the present study in that age and

type of leukemia were not prognostic factors, again

showing that age itself should not be used as the sole

criteria for refusing intensive care. However, the

results for cytogenetics and state of underlying disease

were different between the two studies. The observed

differences between these two studies may be

explained by the differences in the patient population

studied. All patients in the present study had septic

shock whereas less than 50% of patients in the study

by Thakker et al. were on vasopressors. Although the

study by Thakker et al. excluded patients who had

received bone marrow transplant, the present study

did not.

The present study has several limitations. First, it

was a retrospective study performed on patients who

were admitted to the ICU over a 5-year period. Thus,

selection bias and/or the effects of changes in septic

shock management over a long period might have

influenced our data. In addition, the data for some of

Table IV. Results from the multivariate analysis using the Cox-

model for the probability of the ICU mortality*.

Variables in the equation

Variable Coefficient SE p value HR 95% CI

Relapsed/

refractory

status

0.90 0.40 0.026 2.46 1.11–5.42

SOFA 0.22 0.09 0.012 1.25 1.05–1.48

*HR, hazards ratio; CI, confidence interval; SOFA, sequential

organ failure assessment.

Hosmer and Lemeshow: w2¼ 3.46, df 4, p¼ 0.48.

Figure 1. Probability of survival according to the relapsed/

refractory status of the underlying disease. Dotted line, not

relapsed/refractory status (n¼31); solid line, relapsed/refractory

status (n¼19).

Acute leukemia patients with septic shock 1933

Leu

k L

ymph

oma

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

ity o

f C

alif

orni

a Ir

vine

on

11/0

3/14

For

pers

onal

use

onl

y.

the variables, for example, the presence of relative

adrenal insufficiency, were not available for all

patients. Finally, the present study was conducted

at a single centre with a small sample size, which

might influence the statistical power as well as limit

the generalisation of its findings.

In conclusion, although the mortality was high in

patients with acute leukemia who were admitted to

the ICU for septic shock management, it was not

high enough to preclude intensive care. Patients with

severe organ failure and a relapse/refractory status for

leukemia had a significantly worse prognosis.

Declaration of interest: The authors report no

conflicts of interest. The authors alone are respon-

sible for the content and writing of the paper.

References

1. Thomas X, Danaila C, Le QH, Sebban C, Troncy J, Charrin

C, et al. Long-term follow-up of patients with newly diagnosed

adult acute lymphoblastic leukemia: a single institution

experience of 378 consecutive patients over a 21-year period.

Leukemia 2001;15:1811–1822.

2. Jabbour EJ, Estey E, Kantarjian HM. Adult acute myeloid

leukemia. Mayo Clin Proc 2006;81:247–260.

3. Ferra C, Marcos P, Misis M, Morgades M, Bordeje ML, Oriol

A, et al. Outcome and prognostic factors in patients with

hematologic malignancies admitted to the intensive care unit:

a single-center experience. Int J Hematol 2007;85:195–202.

4. Tremblay LN, Hyland RH, Schouten BD, Hanly PJ. Survival

of acute myelogenous leukemia patients requiring intubation/

ventilatory support. Clin Invest Med 1995;18:19–24.

5. Massion PB, Dive AM, Doyen C, Bulpa P, Jamart J, Bosly A,

et al. Prognosis of hematologic malignancies does not predict

intensive care unit mortality. Crit Care Med 2002;30:2260–

2270.

6. Estopa R, Torres Marti A, Kastanos N, Rives A, Agusti-Vidal

A, Rozman C. Acute respiratory failure in severe hematologic

disorders. Crit Care Med 1984;12:26–28.

7. Vandijck DM, Benoit DD, Depuydt PO, Offner FC, Blot SI,

Van Tilborgh AK, et al. Impact of recent intravenous

chemotherapy on outcome in severe sepsis and septic shock

patients with hematological malignancies. Intensive Care Med

2008;34:847–855.

8. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D,

Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS interna-

tional sepsis definitions conference. Crit Care Med 2003;31:

1250–1256.

9. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE,

Calandra T, et al. 2002 Guidelines for the use of antimicrobial

agents in neutropenic patients with cancer. Clin Infect Dis

2002;34:730–751.

10. Knaus WA, Draper EA, Wagner DP, Zimmerman JE.

APACHE II: a severity of disease classification system. Crit

Care Med 1985;13:818–829.

11. Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute

physiology score (SAPS II) based on a European/North

American multicenter study. JAMA 1993;270:2957–2963.

12. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A,

Bruining H, et al. The SOFA (sepsis-related organ failure

assessment) score to describe organ dysfunction/failure. On

behalf of the working group on sepsis-related problems of the

European society of intensive care medicine. Intensive Care

Med 1996;22:707–710.

13. Benoit DD, Vandewoude KH, Decruyenaere JM, Hoste EA,

Colardyn FA. Outcome and early prognostic indicators in

patients with a hematologic malignancy admitted to the

intensive care unit for a life-threatening complication. Crit

Care Med 2003;31:104–112.

14. Brunet F, Lanore JJ, Dhainaut JF, Dreyfus F, Vaxelaire JF,

Nouira S, et al. Is intensive care justified for patients with

haematological malignancies? Intensive Care Med 1990;16:

291–297.

15. Schuster DP, Marion JM. Precedents for meaningful recovery

during treatment in a medical intensive care unit. Outcome in

patients with hematologic malignancy. Am J Med 1983;75:

402–408.

16. Lloyd-Thomas AR, Wright I, Lister TA, Hinds CJ. Prognosis

of patients receiving intensive care for lifethreatening medical

complications of haematological malignancy. Br Med J (Clin

Res Ed) 1988;296:1025–1029.

17. Thakkar SG, Fu AZ, Sweetenham JW, McIver ZA, Mohan

SR, Ramsingh G, et al. Survival and predictors of outcome in

patients with acute leukemia admitted to the intensive care

unit. Cancer 2008;112:2233–2240.

18. Sculier JP, Paesmans M, Markiewicz E, Berghmans T.

Scoring systems in cancer patients admitted for an acute

complication in a medical intensive care unit. Crit Care Med

2000;28:2786–2792.

19. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala

J, Suter PM, et al. Use of the SOFA score to assess the

incidence of organ dysfunction/failure in intensive care units:

results of a multicenter, prospective study. Working group on

‘‘sepsis-related problems’’ of the European society of intensive

care medicine. Crit Care Med 1998;26:1793–1800.

20. Rabbat A, Chaoui D, Montani D, Legrand O, Lefebvre A, Rio

B, et al. Prognosis of patients with acute myeloid leukaemia

admitted to intensive care. Br J Haematol 2005;129:350–357.

21. Cripe LD. Adult acute leukemia. Curr Probl Cancer

1997;21:1–64.

1934 H. Y. Park et al.

Leu

k L

ymph

oma

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

ity o

f C

alif

orni

a Ir

vine

on

11/0

3/14

For

pers

onal

use

onl

y.