Hematopoietic Stem Cell Transplantation in Patients with Systolic Dysfunction: Can It Be Done?

Abstract

Hematopoietic cell transplantation (HCT) is a potential cure for certain hematologic malignancies. However, because of risks of complications and mortality, this treatment option is limited to patients with minimal comorbidities. We performed a retrospective cohort study evaluating the impact of pre-HCT systolic dysfunction on outcomes. We identified 49 subjects with systolic dysfunction, defined as left ventricular ejection fraction (LVEF) < 50% and 49 controls (matched by age, gender, conditioning regimen, and HCT donor number; all with LVEF ≥ 50%) undergoing HCT at the University of Minnesota between 2002 and 2012. Treatment complications, use of beta-blockers and angiotensin-converting enzyme inhibitors, and overall survival (OS) after HCT out to 24 months were analyzed. The median LVEF was 45% (range, 27.5% to 49%) for the study group and 60% (range, 50% to 69%) for controls. The majority of patients in both groups (81.6%) received reduced-intensity conditioning (RIC). Treatment-related mortality (TRM) at day 100 was identical, with a cumulative incidence of 14% in the study (95% confidence interval [CI], 5% to 24%) versus 14% in controls (95% CI, 5% to 24%) (P = .89). Two-year OS was similar in the study group (53%; 95% CI, 38% to 66%) versus controls (61%; 95% CI, 46% to 73%) (P = .34). LVEF ≥ 43% was associated with improved OS at 1 year (hazard ratio [HR], .36; 95% CI, .15 to .87; P = .02). There was no significant difference in the incidence of non–life-threatening cardiac complications (12.2% in cases versus 8.2% in controls, P = .50) or serious (life-threatening or fatal) cardiac complications (4.1% in cases versus 2.0% in controls, P .56). Pre-existing coronary artery disease was associated with increased TRM at 100 days (HR, 4.35; 95% CI,=1.24 to 15.32; P = .02). Cardiac medication use had no effect on TRM. Our study demonstrates that patients with asymptomatic borderline systolic dysfunction can safely undergo HCT with RIC. Coronary artery disease remains a risk factor for increased TRM. Patients with borderline systolic dysfunction can safely undergo HCT, but may need particular vigilance for potential hemodynamic or ischemic cardiac complications.

Impact of comorbidities constituting the hematopoietic cell transplant (HCT)‐comorbidity index on the outcome of patients undergoing allogeneic HCT for acute myeloid leukemia

“…23,24 A reduced left ventricular ejection fraction (LVEF) is considered to be a risk factor for post-transplant cardiac complications; however, the literature is conflicting. [25][26][27][28][29][30] In the present cohort, the prevalence of cardiovascular comorbidity was 12% which was more than twice the 5% quoted by Sorror et al 5 31 In the present cohort, the older age of diabetic patients may account in part for the increased NRM seen in that group. For older patients in particular, pre-existing diabetes is a risk factor for cardiovascular disease, which may add to the risk related to anthracycline administration.…”

Cardiomyopathy in patients after posttransplant cyclophosphamide–based hematopoietic cell transplantation

“…A combination of a decreased resting LVEF and its response to exercise correlates with peritransplant mortality in autologous and allogeneic transplant recipients . Recent reports indicate that patients with pretransplant LVEF values less than 45% to 50% can safely undergo allogeneic transplantation without an increase in treatment‐related mortality, overall survival, or nonrelapse mortality . In the current study, we used existing BNP results to supplement the inclusion of patients with cardiomyopathy.…”

“…19 Recent reports indicate that patients with pretransplant LVEF values less than 45% to 50% can safely undergo allogeneic transplantation without an increase in treatmentrelated mortality, overall survival, or nonrelapse mortality. 20,21 In the current study, we used existing BNP results to supplement the inclusion of patients with cardiomyopathy. It should be noted that a pretransplant assessment of BNP was not performed per protocol but instead according to the practitioner's clinical judgment.…”

Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper

“…47,116 HSCT in patients with decreased LVEF in the range of HF-mid-range reduced ejection fraction is probably feasible. [117][118][119] Therefore, patients who are not eligible for anthracycline-based chemotherapy may still be able to receive HSCT. A patient judged as "unfit for anthracycline and fit for HSCT" could benefit from an alternative induction strategy, as described previously.…”