Abstract
Background:
Allogeneic hematopoietic cell transplantation (HCT) remains standard therapy for various rare, inherited metabolic diseases (IMD). As survival improves, assessment of long-term outcomes is often hampered by patient attrition and distance from treating centers. We piloted a methodology to remotely study parental and/or patient perspectives of adaptive, behavioral, emotional and executive functioning in IMD.
Patients and Methods:
The University of Minnesota BMT Database was queried for surviving IMD patients and disease and transplant characteristics. Parents/patients were invited for study participation. The Research Electronic Data Capture (REDCapª) system was used to electronically administer and retrieve standard and custom survey tools in a one-time cross-sectional analysis (see Table 1). Parents were also asked about their satisfaction with the HCT process/outcomes. Finally, respondents rated independent performance of various activities of daily living (ADL). A Chi-square analysis was performed comparing survey results across post-HCT follow-up tertiles (recent, 1 to 6 years; intermediate, 6 to 16 years; and distant, 16 to 33 years).
Results:
We identified 421 patients transplanted for IMD between 1982 and 2015. Of 239 survivors, 69 (29%) were enrolled (patient only respondents = 3; parent only respondents = 46; both parent/patient respondents = 20). IMD diagnoses included Hurler syndrome (33), adrenoleukodystrophy (17), osteopetrosis (6), metachromatic leukodystrophy (5), and other (8). Forty-seven patients (68%) were male; the median age at HCT was 1.8 years (IQR, 1.1 to 6.5; range, 0.1 to 33.2). Sixty patients (87%) underwent myeloablative conditioning. The stem cell source was UCB in 28 (41%), marrow in 40 (58%) and PBSC in 1 (1%); 52 (75%) received an unrelated graft. Complete donor chimerism was seen in 70%, while 13% were 90-99% engrafted, 9% were 60-89% engrafted, and in 7% of cases engraftment was <60%. The median time from transplant to assessment was 9.2 years (IQR, 3.4 to 17.6; range, 1.1 to 32.8).
Table 1 demonstrates results of a number of the administered tools. Across all administered standardized assessments of executive, emotional and adaptive behavioral functioning (BASC-2, BRIEF, VABS) the majority of patients demonstrated average skills and behaviors when compared to norms for age and gender. A sizable minority showed difficulty on the BASC-2 adaptive skills index with significantly greater difficulty with further time from transplant (p < 0.05). Those with Hurler Syndrome were most likely to be able to attend school, but most required an Individualized Education Plan (IEP). Patients with osteopetrosis showed the most problems with ADLs. Families mostly agreed (88%) that "HCT improved quality of life" for their child and nearly universally endorsed (95%) that "knowing what [they] do now, [they] would choose HCT for [their] child again."
Conclusions: Effective, remote assessment of adaptive, behavioral, emotional and executive function via electronic methods is feasible in a large cohort of IMD patients surviving HCT. At a median follow-up of 9.2 years from HCT, the majority of studied patients had average functioning despite their underlying illness. While patients and their families continue to be impacted by complications of IMD following transplant, they were overall satisfied with the outcomes. Continued follow-up of this patient population is critical to provide appropriate counseling for patients and families considering HCT as a treatment option for IMD.
Table 1. Performance on Standard Measures of Adaptive, Behavioral, Emotional and Executive Functioning for IMD Cohort after HCT Diagnosis BASC-Adaptive Skills BASC- Behavioral Symptoms Index BASC- Emotional Symptoms Index BRIEF- Global Executive Composite VABS-Maladaptive Behavior Index AA/A AR/CS AA/A AR/CS AA/A AR/CS AA/A AR/CS A E CS ALD (%) 44 56 78 22 67 33 63 37 50 40 10 HS (%) 67 33 90 10 100 0 69 31 61 33 6 OP (%) 80 20 100 0 0 0 100 0 100 0 0 Other (%) 67 33 84 16 100 0 67 33 63 25 12 All (%) 63 37 88 12 89 11 69 31 61 31 8 ALD = adrenoleukodystrophy; HS = Hurler Syndrome; OP = Osteopetrosis; AA = Above Average; A = Average; AR = At Risk; CS = Clinically Significant; E = Elevated
Disclosures
No relevant conflicts of interest to declare.
Primary immunosuppressive TNI-based conditioning regimens in pediatric patients treated with haploidentical hematopoietic cell transplantation
