Risk Factors and Outcomes of ICU Admission Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Jamy Omer Hassan , Dasher John , Chen Yanjun , Battles Kevin D. , Salzman Donna , Di Stasi Antonio , Bhatia Ravi , Bhatia Smita 
Published: November 2021

Abstract
Background: Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-hsct) can develop complications such as life-threatening infections, multi-system organ failure, ICU admission and ventilator support in the immediate post-transplant period. Whereas outcomes of these complications, particularly ICU admission and ventilator support, are known to be poor, little is known about the risk factors leading to them.
Methods: We conducted a retrospective study to analyze the impact of pre-transplant risk factors on acute inpatient complications, focusing on ICU admission, ventilator support and multi-system organ failure, following allo-hsct at the University of Alabama at Birmingham (UAB) between 2008 and 2016. Mortality rates and survival outcomes of patients admitted to the ICU were also analyzed. Pre-transplant individual comorbidities were defined as per Sorror's HCT-CI.
Results: There were 304 patients included with a median age of 52y (18-72y). There were 51% male and 82% Non-Hispanic white patients. The most common indication for transplant was AML (45%). Donor type was matched-unrelated, haploidentical and matched-related in 53%, 35% and 12% of cases, respectively. Majority of the patients received myeloablative conditioning (74%). The prevalence of health behaviors and comorbidities at the time of transplant is shown in Table 1. There were 39% patients with HCT-CI score of ≥3, 23% with moderate pulmonary compromise, 22% with a psychiatric disorder, 13% with severe pulmonary compromise, 13% with diabetes mellitus (DM), 10% with cardiac abnormalities and 6% with infection at the time of transplant.
During the initial hospitalization, 33 (11%) patients required ICU admission, 29 (10%) required ventilator support, 33 (11%) developed multi-system organ failure, 79 (26%) developed bacterial infections and 15 (5%) developed fungal infections. The median time to neutrophil engraftment was 13 days (7-48 days).
In multivariable analysis (Table 2), risk factors for ICU admission included pre-transplant infection (HR 6.50, 95% CI 1.82-23.26, p=0.004), pre-transplant DM (HR 4.14, 95% CI 1.56-10.97, p=0.004), time to neutrophil engraftment (HR 1.13, 95% CI 1.05-1.21, p=0.0007), donor type (ref: matched related donor; haplo: HR 0.24 95% CI 0.07-0.82, p=0.02) and HSCT era (ref: 2008-2010; 2010-2013: HR 0.18 95% CI 0.04-0.88, p=0.03; 2014-2016: HR 0.12 95% CI 0.03-0.4, p=0.0006). Risk factors for ventilator support included pre-transplant infection (HR 10.09, 95% CI 2.44-41.64, p=0.001), pre-transplant DM (HR 3.61, 95% CI 1.31-9.91, p=0.01), time to neutrophil engraftment (HR 1.17, 95% CI 1.11-1.23, p&lt;0.0001) and HSCT era (ref: 2008-2010; 2010-2013: HR 0.21 95% CI 0.06-0.81, p=0.02; 2014-2016: HR 0.07 95% CI 0.02-0.31, p=0.0005). Risk factors for multi-system organ failure included pre-transplant DM (HR 4.38, 95% CI 1.64-11.74, p=0.003), time to neutrophil engraftment (HR 1.13, 95% CI 1.08-1.19, p&lt;0.0001) and HSCT era (ref: 2008-2010; 2010-2013: HR 0.21 95% CI 0.05-0.80, p=0.003; 2014-2016: HR 0.16 95% CI 0.05-0.48, p=0.001).Risk factor for bacterial infection included HSCT era (ref: 2008-2010; 2010-2013: HR 0.30 95% CI 0.14-0.65, p=0.002; 2014-2016: HR 0.24 95% CI 0.12-0.49, p&lt;0.0001) and for fungal infection included pre-transplant pulmonary compromise (ref: no compromise; severe pulmonary compromise HR 5.16, 95% CI 1.05-25.4, p=0.04). For patients admitted to the ICU, the 60-day and 6-month mortality was 58% and 67%, respectively. No deaths were attributed to relapse disease. The median overall survival for patients admitted to the ICU was 1.4 months (Figure 1).
Conclusion: Patients with DM and infection at the time of HSCT and delayed neutrophil engraftment during transplant are at an increased risk for ICU admission, ventilator support and multi-system organ failure following allo-hsct. Patients admitted to the ICU are also at a high risk for early mortality leading to poor survival. Optimizing glycemic control and delaying transplant until resolution of infection, if the underlying disease would allow, may help improve both morbidity and mortality in transplant recipients.
Figure 1 Figure 1.

Disclosures
Di Stasi: Syndax Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Alabama at Birmingham: Current Employment.