ABSTRACT
We report on nine children with Shwachman-Diamond syndrome (SDS), eight of whom had clonal abnormalities of chromosome 7. Seven children had an isochromosome 7 [i(7)(q10)] and one a derivative chromosome 7, all with an apparently identical (centromeric) breakpoint. Children with SDS are predisposed to myelodysplasia (MDS) and acute myeloid leukaemia (AML) often with chromosome 7 abnormalities. Allogeneic transplants have been used to treat these children, however, they are a high-risk transplant group and require careful evaluation. Three of the children were transplanted but only one survived, who to our knowledge remains the longest surviving SDS transplant patient (4.5 years +). The six non-transplanted children are well. In classic MDS, chromosome 7 abnormalities are associated with rapid progression to acute leukaemia; however, we present evidence to suggest that isochromosome 7q may represent a separate disease entity in SDS children. This is a particularly interesting finding given that the SDS gene has recently been mapped to the centromeric region of chromosome 7. Our studies indicate that i(7)(q10) is a relatively benign rearrangement and that it is not advisable to offer allogeneic transplants to SDS children with i(7)(q10) alone in the absence of other clinical signs of disease progression.
Subject(s)
Bone Marrow Transplantation , Chromosomes, Human, Pair 7/genetics , Isochromosomes/genetics , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Adolescent , Adult , Child , Child, Preschool , Disease Progression , Failure to Thrive/genetics , Humans , In Situ Hybridization, Fluorescence , Infant , Karyotyping , Patient Selection , SyndromeABSTRACT
The authors describe two pediatric cases of large granular lymphocytosis presenting early in the second decade of life with neutropenia and sepsis. They are among the youngest described in the literature. This report focuses on the advantages of detailed immunophenotypic and molecular analysis and highlights some of the controversies and uncertainties in the management of these patients, particularly the choice of immunosuppressive therapy. Immunosuppressive therapy in the two children described in this report resulted in improvement of neutropenia and clinical status, but this was not accompanied by the disappearance of the clonal population.
