Outcome of patients with hematologic malignancy admitted ... · Outcome of patients with...

Outcome of patients with hematologic malignancy admitted to the ICU

Geeta Mehta MD, FRCPC

Mount Sinai Hospital

Toronto, Canada

CCCF

November 2, 2016

Disclosures

Hematologic Malignancy

• Advances in diagnostics, risk stratification and treatment regimens including hematopoietic cell transplantation (HCT)

• Aggressive treatment has been extended to higher risk candidates: older, more comorbid illness, receiving salvage chemotherapy

• More dose-intensive regimens, or novel approaches to HCT (mismatched, haploidentical, cord blood transplant )

• As a consequence, there has been an increased risk of serious complications and need for ICU care.

Complications

• Infectious

• Chemotherapy related

• HCT related

• Bleeding

• Acute respiratory failure

• GVHD

• Sinusoidal Obstructive syndrome

• etc…

ICU survival has improved

• In 1999, the American College of Critical Care Medicine stated: ‘patients with HM are poor candidates for ICU admission with a mortality rate of up to 90%. Immediate treatment limitation/refusal of ICU admission is advocated’ (Crit Care Med 1999)

• Recent reports showing improved ICU survival rates challenge this perception

• Mount Sinai Hospital

– Between 2012 and 2015, 420 patients from Princess Margaret Hospital were admitted to ICU

– ICU mortality 32%

• > 500 ICU admissions annually in Canada

We need more data

• More multi-center and population studies are needed to evaluate outcomes and predictors

• Functional outcomes

• Patient and family perspectives

• Advance Care Planning

• Clinical Practice Guidelines

AJRCCM 2016

age > 66 yrICU LOS >2 wk

• Retrospective chart review

• 151 consecutive patients with AML and ALL admitted to Mount Sinai Hospital Medical-Surgical ICU, a 16-bed ICU affiliated with the University of Toronto

• 2009 to 2012

• Objective: to describe ICU interventions, short and long-term outcomes, and predictors of outcome

Patient Characteristics

Age, years 54 (15)

Female 76 (50%)

APACHE II 27 (22-33)

SOFA 10 (8-13)

MODS 7 (6-10)

Neutropenia (<500) 84 (74)

Thrombocytopenia (<50) 126 (86)

Admission Diagnosis

Sepsis 74 (49)

Respiratory 46 (31)

Cardiovascular Failure 14 (10)

Gastrointestinal Bleed 3 (2)

Neurological Dysfunction 8 (5)

N (%)

Leukemia Type

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

118 (78)

33 (22)

Chemotherapy Stage

Induction

Consolidation

Intensification Phase

Reinduction for Relapse

Reinduction for Non-response

Not Provided Chemotherapy within 40 days

No Pharmacy Records

55 (36)

9 (6)

5 (3)

29 (20)

12 (8)

33 (22)

3 (2)

Leukemia Factors

CNS Infiltration

HCT before ICU

Allogeneic

Autologous

GVHD

9 (6)

20 (13)

17

3

11 (7)

Leukemia Characteristics (N=151)

Outcomes

ICU stay 4 days (2-8)

Survival

ICU 62%

30-day 49%

90-day 40%

6 months 34%

12 months 25%

Characteristics of ICU survivors and non-survivors at ICU

discharge and 1-year post ICU admission

Characteristics of ICU survivors and non-survivors at ICU

discharge and 1-year post ICU admission

Multivariable analysis of independent predictors of

ICU mortality

VariableOdds Ratio Estimates

(95% CI)P Value

SOFA

Induction Stage at ICU admission

Relapse Stage at ICU admission

Age

Septic Shock

Invasive Ventilation

1.18 (1.01-1.38)

0.43 (0.16-1.17)

0.49 (0.14-1.66)

1.01 (0.98-1.05)

4.06 (0.97-7.50)

9.64 (3.39-27.40)

0.03

0.09

0.25

0.39

0.057

<0.001

Other Canadian studies

Study Patients N ICU

Mortality

1 year

mortality

Krajuljak AML/ALL 151 38% 75%

Cornish 2016 HM 206 45% 74%

Roze des Ordons 2010 AML 45 44% 71%

Trinkaus 2009 Auto-SCT 34 38%

Scales 2008 HCT 504 74%

Crit Care

2008

• OHIP database

• Adults (>18 years) who underwent BMT1992 to 2002

Internationally - Single center studies

Study Country Patients N ICU

Mortality

1 year

mortality

Kroschinsky 2002 Germany HCT 104 44% 71%

Massion 2002 Belgium HM 84 38 75%

Afessa 2003 US HCT 112 33

Rabbat 2005 France AML 83 34 49%

Bruennler 2007 Germany HM 94 43

Ferra 2007 Spain HM 100 49

Thakkar 2008 US AL 90 68

Silva 2013 Mexico HM 102 46

Bird 2012 UK HM 199 34

Hill 2012 UK HM 147 73

Hampshire 2014 UK – 3

centers

HM 187 49

Medic 2015 Croatia HM 170 54

Grrr-OH: Groupe de recherche respiratoire en réanimation

onco-hématologique

17 centers in France and Belgium

Study Patients N ICU Mortality Hospital

Mortality

Azoulay 2013 HM 1011 39%

Lengline 2015Allo-HCT 497 51% 90-day

Mokart 2015 Neutropenic 289 45% 75%

Lemiale 2015 HM - ARF 382 32%

Darmon 2015 HM - AKI 671 38%

Independent Predictors of Mortality

• Azoulay 2013: Poor performance status, Charlson

comorbidity index, allogeneic HSCT, organ dysfunction

score, cardiac arrest, acute respiratory failure, malignant

organ infiltration, and invasive aspergillosis

• Mokart 2015: allogeneic HCT (OR 3.83; 95 % CI 1.75–

8.35), MV (OR 6.57; 95 % CI 3.51–12.32),

microbiological documentation (OR 2.33; CI 1.27–4.26),

RRT (OR 2.77; 95 %CI 1.34–5.74)

• Lengline 2015: GVHD, MV, RRT

• Darmon 2015: AKI (OR 1.65, 95% CI 1.19-2.29)

Summary

• Patients with hematologic malignancy

– ICU mortality 40%; 1 year mortality as high as 75%

• Not possible to predict outcome with 100%

certainty

• Cannot justify denying these patients ICU

admission

• Independent predictors of mortality vary

– Pre-morbid functional status may be as

important as HM and acute illness variables

Urgently needed…

• Multicenter outcome studies on patients with HM who require ICU admission

• Population based data on survival and functional outcomes

• Comprehensive evaluation of the factors contributing to long term morbidity in patients who survive their critical illness

• Patients, families, and clinicians will benefit from knowing which patients survive, and the challenges faced by survivors and their families

JAMA 2016

COHOCritical Care Outcomes of Patients with

Hematologic Malignancy or Hematopoietic

Cell Transplant

Vision: To become a world class centre

in providing critical care services to

oncological patients

Mission: To provide the best critical care

for oncological patients by having optimal

knowledge, communication, and

research development through

collaborations of all stakeholders

Focus on:

1. Clinical Knowledge

2. Education

3. Research

4. Quality Improvement

Examples of Projects by COIN Members

AFI TOPIC

1 Acute Promyelocytic Leukemia

Outcomes Study

2 Interhospital Transfer

3 Intrahospital Transfer

4 Data Mapping

5 Medications (Tumor Lysis Mgt)

6 Education

7 Advance Care Planning

8 Blood Bank

9 Hickman Line

10 Hypoxia post BMT

Quality Improvement Initiative

Critical Care Oncologic Investigative Network

(COIN)

Intensivists Patients

Family Members

Palliative care

Hematologists

Transplant

physicians

Rehab

specialistsDieticians

Pharmacists

Spiritual

Care

Thank-you!

Geeta.Mehta@utoronto.ca