Distinct Patterns of Marrow Fibrosis in Patients with Inherited Bone Marrow Failure Syndromes
I Maric, N Giri, D Arthur, P Noel, BP Alter. CC/NIH, Bethesda, MD; NCI/NIH, Bethesda, MD
Background: There are no data on the incidence or significance of bone marrow fibrosis in patients with the inherited bone marrow failure syndromes (IBMFS), genetic disorders characterized by cytopenias, distinctive clinical features, varied molecular pathways and high risk of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). We studied marrow fibrosis in the four most common IBMFS: Fanconi anemia (FA), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS) and dyskeratosis congenita (DC).
Design: We performed a retrospective study of 42 bone marrow biopsies from patients with established diagnoses of IBMFS. Blinded biopsies from 13 DBA, 13 DC, 12 FA, and 4 SDS patients were analyzed. Reticulin fibrosis was graded on a scale of 1-4 according to the quantity and pattern of distribution of reticulin. The frequencies of abnormalities in marrow fibrosis, cellularity, MDS, cytogenetic clones, blood counts, and need for treatment were compared between the disorders.
Results: See Table. Significantly more patients with DC or FA had increased reticulin fibrosis (grade 2 or 3) compared with DBA or SDS. No patient had grade 4 fibrosis, and grade 3 was present only in 2 FA patients. Marrow hypocellularity was present in all DC and FA and less frequent in SDS or DBA. MDS and cytogenetic clones were not seen in DBA. Cytogenetic clones were more frequent in SDS and FA then in DC, while the frequency of cytopenias and hematologic treatment was consistent with the underlying diagnoses.
|IBMFS||BM fibrosis N(%)||BM Hypocellularity N(%)||Morphologic MDS/Cytogenetic Clone N(%)||Thrombocytopenia N(%)||Neutropenia N(%)||Anemia N(%)||On Treatment N(%)|
|DBA n=13||2 (15)||5 (38)||0 (0)/0 (0)||0 (0)||3 (23)||9 (69)||9 (69)|
|DC n=13||10 (77)||13 (100)||1 (8)/2 (15)||11 (85)||7 (54)||7 (54)||7 (54)|
|FA n=12||9 (75)||12 (100)||3 (25)/6 (50)||8 (67)||8 (67)||4 (33)||5 (42)|
|SDS n=4||1 (25)||2 (50%)||2 (50)/3 (75)||3 (75)||4 (100)||0 (0)||0 (0)|
|P value (DC/FA/SDS)vsDBA||0.002||<0.001||NS/0.01||<0.001||0.02||NS||NS|
Conclusions: The incidence of grade 2 or 3 bone marrow fibrosis is as high as 75% in DC and FA, and much less common in DBA and SDS. Marrow hypocellularity, MDS, cytogenetic abnormalities and pancytopenia are rare in DBA but common in the other IBMFS. Longitudinal studies are required to determine the prognostic significance of these findings.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 201, Wednesday Afternoon