Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.

OBJECTIVE: The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation. MATERIALS AND METHODS: Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed. RESULTS: Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed. CONCLUSIONS: A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.

Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation.

PURPOSE: To report a patient with a phenotype suggestive of Gillespie syndrome and with a chromosomal abnormality. METHODS: Clinical evaluation showed bilateral superior coloboma, foveal hypoplasia, and inferior cerebellar hypoplasia. Karyotyping as well as investigation of the PAX6 gene were performed. RESULTS: The karyotype of the patient disclosed a de novo translocation t(X;11)(p22.32;p12). Fluorescent in situ hybridization and the search for mutations excluded direct implication of the PAX6 gene. CONCLUSION: This is, to our knowledge, the first report of a chromosomal abnormality detected in a patient with a Gillespie syndrome phenotype.

Deletions of distal 9p associated with 46,XY male to female sex reversal: definition of the breakpoints at 9p23.3-p24.1.

Monosomy of distal 9p is associated in rare cases with abnormalities of testicular determination, which can lead to male to female sex reversal in a 46,XY genetic background. We present two 46,XY individuals partially monosomic for 9p who were raised as females. Definition of the breakpoints using somatic cell hybrids containing only the rearranged chromosome 9 indicated that in the first patient the breakpoint was located between markers D9S256 and D9S144 and in the second patient, the breakpoint was distal to the marker D9S144. In both cases this corresponds to the cytogenetic position 9p23.3-p24.1. Analysis of highly polymorphic microsatellite markers demonstrated a paternal origin of the rearranged chromosome 9 in both patients. These studies define the minimum region associated with male to female sex reversal as 9p24.1-pter.