Morphologic Changes in Myelodysplastic Syndrome Treated with Hypomethylating Agents
Shannon K Rathke, Horatiu Olteanu, Steven H Kroft, Alexandra M Harrington. Medical College of Wisconsin, Milwaukee, WI
Background: Hypomethylating agents (HMAs) are frequently used as myelodysplastic syndrome (MDS) therapy. As little data exists on the morphologic changes observed with this treatment in peripheral blood (PB) and bone marrow (BM), we chose to study this in a MDS cohort.
Design: PBs and BMs from MDS patients were evaluated before (PTx) and after (F/U) HMA treatment. Cell counts, lineage dysplasia, blast percentages, and BM cellularity, stromal changes, lymphoid aggregates, bony changes, and hemosiderin deposition were recorded. The MDS diagnosis was made according to WHO 2008 criteria. Dysplasia was defined as morphologic abnormalities present in >10% of a lineage.
Results: 13 MDSs were included: 6 therapy-related MDSs, 4 MDS-unclassifiable, 2 refractory anemia with excess blasts and 1 refractory cytopenia with multilineage dysplasia; 7 males, 6 females; aged 35-79. Median PTx CBC data was 2.6k/μL WBCs (1.1-8.5), 9.2g/dL Hgb (7.2-12.4) and 105k/μL (25-292) Plts, compared to 2.3k/μL (0.57-6.6) WBCs (p=0.612), 10g/dL (8.6-13.1) Hgb (p=0.114), and 108k/μL (11-558) Plts (p=0.872) in F/Us. Median time between PTx and F/U analysis was 115 days (44-507). 5 PTx cases had PB blasts, which were not present at F/U. PB granulocyte dysplasia persisted in 3/5 cases and resolved in 2/5 at F/U; erythroid dysplasia resolved in 4/6 cases; and PLT dysplasia resolved in 4/5 cases. One case acquired PB granulocyte dysplasia at F/U. BM blasts averaged 3% (1-12%) PTx compared to 1.6% (0-14%) at F/U (p=0.06). Average cellularity was 61% (<5-100%) in PTx vs. 29% (<5-75%) in F/U (p=0.009). BM granulocyte dysplasia persisted in 5/7 cases at F/U; erythroid dysplasia persisted in 5/8 cases and resolved in 3/8; megakaryocyte dysplasia persisted in 10/11 cases and was lost in 1/11 cases at F/U. One case each gained BM granulocyte and erythroid dysplasia at F/U. 6 cases had PTx ring sideroblasts, which persisted in all cases at F/U. Following HMAs, 1 case showed stromal degeneration, 2 cases developed fibrosis, 2 cases gained lymphoid aggregates, 5 cases developed bony changes, and 8 cases showed increased hemosiderin deposition.
Conclusions: Blast percentages decreased in both the PB and BM following HMA therapy. Decreased BM cellularity was observed at F/U. The most common morphologic changes observed were loss of erythroid and platelet dysplasia in the blood. Despite decreased blast counts and BM cellularity, granulocyte, megakaryocyte, and erythroid dysplasia persisted in the marrow in the majority of cases. Stromal degeneration and fibrosis occur, but are uncommon findings post-therapy.
Monday, March 19, 2012 1:00 PM
Poster Session II # 234, Monday Afternoon