Long-Term Organ Function After HCT for SCD: A Report From the Sickle Cell Transplant Advocacy and Research Alliance.

Hematopoietic cell transplantation (HCT) is an established cure for sickle cell disease (SCD) supported by long-term survival, but long-term organ function data are lacking. We sought to describe organ function and assess predictors for dysfunction in a retrospective cohort (n = 247) through the Sickle cell Transplant Advocacy and Research alliance. Patients with <1-year follow-up or graft rejection/second HCT were excluded. Organ function data were collected from last follow-up. Primary measures were organ function, comparing pre- and post-HCT. Bivariable and multivariable analyses were performed for predictors of dysfunction. Median age at HCT was 9.4 years; the majority had HbSS (88.2%) and severe clinical phenotype (65.4%). Most received matched related (76.9%) bone marrow (83.3%) with myeloablative conditioning (MAC; 57.1%). Acute and chronic graft-versus-host disease (GVHD) developed in 24.0% and 24.8%. Thirteen patients (5.3%) died ≥1 year after HCT, primarily from GVHD or infection. More post-HCT patients had low ejection or shortening fractions than pre-HCT (0.6% â†’ 6.0%, P = .007 and 0% â†’ 4.6%, P = .003). The proportion with lung disease remained stable. Eight patients (3.2%) had overt stroke; most had normal (28.3%) or stable (50.3%) brain magnetic resonance imaging. On multivariable analysis, cardiac dysfunction was associated with MAC (odds ratio [OR] = 2.71; 95% confidence interval [CI], 1.09-6.77; P = .033) and severe acute GVHD (OR = 2.41; 95% CI, 1.04-5.62; P = .041). Neurologic events were associated with central nervous system indication (OR = 2.88; 95% CI, 2.00-4.12; P < .001). Overall organ dysfunction was associated with age ≥16 years (OR = 2.26; 95% CI, 1.35-3.78; P = .002) and clinically severe disease (OR = 1.64; 95% CI, 1.02-2.63; P = .043). In conclusion, our results support consideration of HCT at younger age and use of less intense conditioning.

Late toxicity of a novel allogeneic stem cell transplant using single fraction total body irradiation for hematologic malignancies in children.

Single fraction total body irradiation (SFTBI) as part of a myeloablative preparative regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies was shown to have similar survival compared with fractionated total body irradiation (FTBI)-containing regimens, with less acute toxicity. The objective of this study was to determine long-term toxicity >2 years following SFTBI-based HSCT. Twenty-one patients were evaluated at a median follow-up of 6.8 years. Thyroid dysfunction was found in 21% of patients, 1 of whom (5.2%) was symptomatic; 23% had gonadal failure; 50% of patients with growth potential had linear growth disturbance; 27% had mild to moderate pulmonary disease; and 25% had cataracts. Intelligence quotient was stable. cGVHD was present in 28%, and 4 patients (19%) were on immune suppression 2 years posttransplant. Overall survival subsequent to 2 years posttransplant was 76% in this cohort of patients. No secondary malignancies were observed. In conclusion, the toxicities of SFTBI occurred at similar or reduced frequency compared with FTBI. SFTBI should be considered for patients who may benefit from a radiation-containing HSCT preparative regimen.