Hematopoietic Cell Transplantation in Patients with Systolic Heart Failure: Can It be Done?

Introduction:

Hematopoietic cell transplantation (HCT) is a potential cure for certain hematologic malignancies.  However due to risks of complications and mortality, this treatment option is limited to patients with minimal co-morbidities.  There are few data on patients with systolic heart failure undergoing HCT.  We performed a case control study evaluating the impact of pre-HCT systolic heart failure on outcomes. 

Methods:

We studied 49 subjects with systolic heart failure defined as left-ventricular ejection fraction (LVEF) <50% and 49 controls (matched by age, gender, conditioning regimen, and HCT donor number) with LVEF >= 50% undergoing HCT at the University of Minnesota between 2002-2012.  Treatment complications and mortality at 100 days, as well as overall survival (OS) after HCT at 100 days, 12 months and 24 months were determined including use of beta-blockers and angiotensin converting enzyme (ACE) inhibitors. 

Results:

The median pre-transplant age was 51.9 (19.1-69.2) years in the study group and 54.5 (20.7-72.5) years in the controls; each including 31 males (63.3%) and 18 females (36.7%).  In both groups, 9 patients (18.8%) received myeloablative conditioning regimen and 39 (81.3%) had reduced intensity conditioning.  The median LVEF was 45% (27.5-49%) for the study group and 60% (50-69%) for the control.  Beta-blocker use at the time of HCT (32.7% in the study group vs. 4.1% in the control; p<0.01) and ACE-inhibitor use (30.6% in the study group vs. 6.1% in the control; p<0.01) was more common in the study group compared to the control. Treatment related mortality (TRM) at day 100 was identical with a cumulative incidence of 7 in the study (RR 15%, 95% CI 5-24%) and 7 in the control (RR 15%, 95% CI 5-25%) (p=0.88). There was no significant difference in the 2-year OS between the study group (n=26, 53%, CI 38-66%) compared to the control group (n=30, 61%, CI 46-73%) (p= 0.34).  An LVEF >/= 43% was a threshold for improved OS at 1 year (HR 0.36, 95% CI 0.15-0.87; p=0.02).  There was no significant increase in the incidence of minor (non-life-threatening) cardiac complications (12.2% in the study vs. 8.2% in the control, p=0.50) or serious (life-threatening or fatal) cardiac complications (4.1% in the study group vs. 2.0% in the control, p=0.56) between groups.  The use of beta-blockers (HR 2.35, 95% CI 1.12-4.93, p=0.02) and ACE-inhibitors (HR 2.96 (1.44-6.10) , 95% CI 1.44-6.10, p<0.01) was associated with worse OS at 1 year.   

Conclusion:

 Our results suggest that patients with reduced systolic heart function should not be excluded from HCT.  Additionally, the role of beta-blockers and ACE-inhibitors in this population is not clear and requires further study.