The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.
Investigators reviewed medical records of infants with LALD and summarized data for the ...overall population and for patients with and without early growth failure (GF). Kaplan–Meier survival analyses were conducted for the overall population and for treated and untreated patients.
Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).
These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.
Children with cancer and HSCT recipients are at high risk for common viral infections. We sought to define the viral etiology of ARI and identify risk factors. Nasal wash samples were collected from ...pediatric hematology–oncology patients and HSCT recipients with ARI during the 2003–2005 winter seasons. Real‐time RT‐PCR was performed to detect Flu A, influenza B, RSV, PIV 1‐3, human MPV, and HRV. HRV specimens were sequenced and genotyped. Seventy‐eight samples from 62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV were detected most frequently, in 16 (52%) including five HRVC; followed by seven (22%) RSV, five (16%) Flu A, four (13%) MPV, and two (6%) PIV2. There was a trend toward higher risk of viral infection for children in day care. Only 8% of the study children had received influenza vaccine. HRV, including the recently discovered HRVC, are an important cause of infection in pediatric oncology and HSCT patients. Molecular testing is superior to conventional methods and should be standard of care, as HRV are not detected by conventional methods.
Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-threatening manifestations. BCL11A is a transcription factor ...that represses γ-globin expression and fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem and progenitor cells obtained from healthy donors, with CRISPR-Cas9 targeting the
erythroid-specific enhancer. Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients - one with TDT and the other with SCD - received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same
enhancer. More than a year later, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, transfusion independence, and (in the patient with SCD) elimination of vaso-occlusive episodes. (Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.).
Studies have shown second allogeneic hematopoietic stem cell transplant (HSCT) to have a potential role in treating relapse after HSCT. We sought to evaluate the outcome of second allogeneic HSCT for ...children with relapsed leukemia with focus on factors that potentially improve outcome. Thirty-eight children were identified. The median time between transplants was 18.6 months (range 6.7-50.1 months). With median follow-up of 44 months the 2-year overall survival (OS) was 59.1 ± 8.2%. The leukemia-free survival was 51.8 ± 8.2% and the non-relapse mortality 30.8 ± 7.9%. Eleven patients (30%) died of non-relapse mortality at a median of 37 days (range 16-260 days) from second HSCT. Twenty-one patients developed acute graft-versus-host disease (aGVHD) after second HSCT. Patients who developed aGVHD had lower risk for mortality compared to patients who did not have aGVHD, with a hazard ratio (HR) of 0.27 (95% confidence interval CI 0.095-0.788, p-value 0.0163). Similarly, patients who developed aGVHD following second HSCT had lower risk for relapse (HR = 0.21, 95% CI 0.051-0.857, p-value 0.0297). Patients who developed aGVHD after first HSCT were less likely to benefit from second HSCT compared to patients without aGVHD after first HSCT. Our experience suggests that second HSCT for pediatric relapsed leukemia can result in acceptable survival and aGVHD is associated with improved outcome.
Several cytogenetic abnormalities identified in patients with childhood acute lymphocytic leukemia (ALL) have been associated with a poor prognosis. There are several case reports in the literature ...describing t(17;19) in children with ALL. This translocation has been associated with hypercalcemia, coagulopathy, and poor outcome. We present three cases of ALL with t(17;19) treated at our institution and review the outcome of children reported in the medical literature.
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