Background: Hematopoietic cell transplantation (HCT) is currently the only proven curative treatment for sickle cell disease (SCD), with >90% event-free survival using a matched related donor (MRD). Long-term follow up in patients transplanted for malignant disease demonstrates a 4-fold increase in risk of developing cardiovascular disease (CVD). Risk factors for CVD include obesity, hypertension, diabetes, and dyslipidemia, which are reported in a higher incidence in both survivors of HCT and childhood malignancy. While patients with SCD typically have lower weight and blood pressure (BP) for age, cure of SCD may lead to decreased metabolic demand as well as increased weight and BP, thus uniquely predisposing post-transplant SCD subjects to CVD risk. Further, because of premature mortality due to SCD, true risk of CVD in these patients may be unknown.

Objective: To investigate the development of CVD risk factors in SCD subjects who underwent HCT with myeloablative conditioning.

Methods: We performed a retrospective data collection on SCD subjects who underwent allogeneic HCT at Children's Healthcare of Atlanta (CHOA) and survived to ³1 year post-HCT. Data on baseline patient and transplant characteristics as well as CVD risk factors (body mass index [BMI], BP, and cholesterol) were collected. BMI was categorized per CDC definition as underweight (<5th%), healthy weight (5th% to <85th%), overweight (85th% to <95th%), or obese (≥95th%). BP was categorized as >50th% and >90th% for patients with SCD, as per Table 1 in Pegelow et al. Pre- and post-HCT values were compared using Wilcoxon signed-rank tests or McNemar's tests, with p-values <0.05 considered statistically significant.

Results: Sixty-seven SCD subjects underwent allogeneic HSCT from December 1993 to March 2016 at CHOA, 63 of whom survived to ≥1 year post-transplant. Fourteen patients did not have pre- or post-HCT BMI data available, thus were excluded from the analyses. Majority had clinically severe SCD (77.8%) and received bone marrow (93.3%) from a matched sibling donor (91.1%). Conditioning was myeloablative in all, majority using a combination of busulfan, cyclophosphamide, and anti-thymocyte globulin ± fludarabine. Patients underwent HCT at a median age of 8.8 years (range 1.8-20.3), at which time 40 (88.9%) were healthy weight, while 3 of each (6.7%) were underweight, overweight, and obese (Table 1). At last follow up (median age 10.3 years; range, 3.8-21.8), 27 patients (60.0%) were healthy weight, while 6 (13.3%) were underweight, 5 (11.1%) overweight, and 7 (15.6%) obese. When pre- and post-transplant BMI categories were compared, 66.7% of patients had no change, whereas 17.8% increased and 15.6% decreased. Of the 8 patients whose BMI category increased, 6.7% became overweight and 11.1% obese. Of the 7 patients who BMI category decreased, 2 obese patients (28.6%) became overweight, 2 overweight patients (28.6%) became obese, and 3 normal weight patients (42.9%) became underweight. BMI significantly increased from a median of 16.2 kg/m2 pre- to 19.0 kg/m2 post-HCT (p<0.001). There was no increase in the proportion of patients exceeding either the 50th or 90th percentile for systolic BP post-HCT (Figure 1). The proportion with diastolic BP exceeding 50th or 90th percentile for age for SCD was increased post-HCT compared to baseline. Five patients were diagnosed with hypertension ≥6 months post-transplant, 4 of whom were receiving treatment for chronic graft-versus-host disease (GVHD; steroids, cyclosporine [CSA], or steroids plus CSA) and 1 of whom was overweight. Routine cholesterol testing was rare, consistent with a pediatric cohort, with only 2 patients having hypercholesterolemia, both of whom were receiving treatment for chronic GVHD. Two patients had mildly elevated hemoglobin A1c levels post-HCT and none were diagnosed with diabetes. Ten patients developed chronic GVHD (22.0%), 8 of whom remained in a stable BMI category, with 1 of each either increasing or decreasing.

Discussion: Following successful HCT, patients with SCD developed relative diastolic hypertension and increased BMI, both of which are known risk factors for CVD. Patients who developed chronic GVHD were more likely to be diagnosed with hypertension and/or hypercholesterolemia, although BMI category was not impacted. These data provide the rationale for longer term follow up for CVD risk factors and CVD in patients with SCD following HCT.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.