Impaired B-Cell Development Can Predict Chronic Graft-Versus-Host Disease in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
Kelley Mast, M Rizwan Khawaja, Anupama Tewari, Mehdi Nassiri, Shanxiang Zhang, Jiehao Zhou, Robert P Nelson, Magdalena Czader. Indiana University School of Medicine, Indianapolis, IN
Background: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT) and together with immunosuppressive therapy is implicated in the impaired immune reconstitution. Select parameters of immune function and their relation to the clinical outcomes including GVHD have been previously studied. However, only rare reports explore the relationship between early bone marrow (BM) morphologic and immunophenotypic findings and the incidence of GVHD. In this study, we evaluated the histopathologic features of bone marrow biopsies and lymphocyte subpopulations in a cohort of patients post allogeneic HCT, and compared these to the development of acute and chronic GVHD (aGVHD and cGVHD).
Design: Post-HCT BM specimens and blood counts at day +30 and/or day +100 were retrospectively examined in 98 patients who received either myeloablative or nonmyeloablative HCT for acute myeloid leukemia or myelodysplastic syndrome. BM biopsy and aspirate smear examination included the following: % cellularity, % adipocytes, activated osteoblast morphology, paratrabecular fibrosis, trabecular remodeling, new bone formation, the presence of osteoclasts, myeloid:erythroid ratio, % lymphocytes and % hematogones. Bone marrow lymphocyte subsets (CD20+ B-cells, CD3+ T-cells, CD4+ and CD8+ T-cells, NK-cells and stage I hematogones) were quantitated by flow cytometry. These results were correlated with laboratory data, and the presence or absence of aGVHD and cGVHD.
Results: The study included 98 patients (49 males and 49 females; median age 48; age range 17-67 years). There were 32 and 39 patients with aGVHD and cGVHD, respectively. Patients with cGVHD had significantly lower numbers of stage I hematogones (p<0.001; mean 2.9% and 8.1% for patients with and without cGVHD respectively). cGVHD was also associated with higher BM adiposity (mean 45% vs 36% without cGVHD; p=0.02). There was a trend for lower cellularity in those with cGVHD (p=0.05). Other morphologic parameters were not statistically significantly different between cases with and without cGVHD. There was also no correlation between histopathologic parameters and lymphocyte subsets, and the presence of aGVHD.
Conclusions: These findings demonstrate that there is an increased incidence of cGVHD among post-HCT patients with lower numbers of stage I hematogones, increased replacement of the BM space with adipocytes and lower cellularity. Further studies are needed to determine whether monitoring of these parameters can be useful in guiding GVHD prophylaxis.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 238, Wednesday Afternoon