title: Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome?
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.
authors.affiliation: Ninewells Hospital and Medical School, Dundee, Western General Hospital, Edinburgh, UK. joancunningham66@yahoo.co.uk
authors.forename: Joan
authors.initials: J
authors.lastname: Cunningham
authors.forename: Mark
authors.initials: M
authors.lastname: Sales
authors.forename: Andrew
authors.initials: A
authors.lastname: Pearce
authors.forename: Julie
authors.initials: J
authors.lastname: Howard
authors.forename: Ray
authors.initials: R
authors.lastname: Stallings
authors.forename: Nicholas
authors.initials: N
authors.lastname: Telford
authors.forename: Rosalie
authors.initials: R
authors.lastname: Wilkie
authors.forename: Brian
authors.initials: B
authors.lastname: Huntly
authors.forename: Angela
authors.initials: A
authors.lastname: Thomas
authors.forename: Aengus
authors.initials: A
authors.lastname: O'Marcaigh
authors.forename: Andrew
authors.initials: A
authors.lastname: Will
authors.forename: Norman
authors.initials: N
authors.lastname: Pratt
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018450:Disease Progression; D005183:Failure to Thrive / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D018404:Isochromosomes / Q000235:genetics*; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000628:therapy*; D018579:Patient Selection; D013577:Syndrome