Search

Additional file 1. The Additional File contains the details of the study methodology and results of the enrichment analysis, including data retrieval, HLA typing, identification of HLA alleles enriched and associated with asparaginase hypersensitivity, and statistical analysis.

Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT.

We report three cases of homozygous α-thalassemia (αTH) who survived beyond the neonatal period, all with hypospadias. A review of literature identified two additional male cases of homozygous αTH who survived, and both had hypospadias. The simultaneous occurrence of the two conditions seems beyond coincidence and may be causally related. Possible pathogenesis for the association may be 1) homozygous αTH-induced in utero and/or edema secondary to hydrops fetalis, both leading to the failure of proper fusion of the urogenital folds, or 2) defect of another gene located at a chromosome 16p13.3 region. Thus, parents who request intrauterine therapy for a male fetus with homozygous αTH should be informed about this association and its prognosis. Am. J. Med. Genet. 82:225–227, 1999. © 1999 Wiley-Liss, Inc.

Background: The aim of this study was to investigate the potential of infrared (IR) spectroscopy as a fast and reagent-free adjunct tool in the diagnosis and screening of β-thalassemia. Methods: Blood was obtained from 56 patients with β-thalassemia major, 1 patient with hemoglobin H disease, and 35 age-matched controls. Hemolysates of blood samples were centrifuged to remove stroma. IR absorption spectra were recorded for duplicate films dried from 5 μL of hemolysate. Differentiation between the two groups of hemoglobin spectra was by two statistical methods: an unsupervised cluster analysis and a supervised linear discriminant analysis (LDA). Results: The IR spectra revealed changes in the secondary structure of hemoglobin from β-thalassemia patients compared with that from controls, in particular, a decreased α-helix content, an increased content of parallel and antiparallel β-sheets, and changes in the tyrosine ring absorption band. The hemoglobin from β-thalassemia patients also showed an increase in the intensity of the IR bands from the cysteine −SH groups. The unsupervised cluster analysis, statistically separating spectra into different groups according to subtle IR spectral differences, allowed separation of control hemoglobin from β-thalassemia hemoglobin spectra, based mainly on differences in protein secondary structure. The supervised LDA method provided 100% classification accuracy for the training set and 98% accuracy for the validation set in partitioning control and β-thalassemia samples. Conclusion: IR spectroscopy holds promise in the clinical diagnosis and screening of β-thalassemia.