Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome?
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.
Cunningham
Joan
J
Ninewells Hospital and Medical School, Dundee, Western General Hospital, Edinburgh, UK. joancunningham66@yahoo.co.uk
Sales
Mark
M
Pearce
Andrew
A
Howard
Julie
J
Stallings
Ray
R
Telford
Nicholas
N
Wilkie
Rosalie
R
Huntly
Brian
B
Thomas
Angela
A
O'Marcaigh
Aengus
A
Will
Andrew
A
Pratt
Norman
N
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