Burst-forming unit–erythroid assays to distinguish cellular bone marrow failure disorders

Abstract

Patients with cytopenias and a cellular bone marrow can be a diagnostic and a therapeutic challenge. Previous reports have suggested a role for progenitor assays as a potentially useful test for diagnosis and predicting response to therapy. Here we report the results of BFU-E assays in 48 consultative cases of single or multi-lineage cytopenias with cellular marrows. The final diagnoses included 17 patients with myelodysplastic syndrome (MDS); 9 patients with pure red cell aplasia (PRCA) [non-large granular lymphocytosis (LGL) in etiology]; 15 patients with LGL (8 of which had a single lineage cytopenia only while the other 7 had multi-lineage cytopenias); and 7 patients with cytopenias associated with systemic inflammation related to autoimmune conditions. In this cohort, nonmalignant diseases were well-distinguished from MDS by BFU-E growth. Our data suggest that low BFU-E growth (less than 10 BFU-E /105 marrow mononuclear cells) helps to exclude LGL, PRCA, or cytopenias associated with systemic inflammation as a cause of pancytopenia with a sensitivity of 96.8%, specificity of 76.5% and a predictive value of 88.2% (p=0.0001). BFU-E growth was also examined to predict response to treatment. Of the 29 patients in this cohort treated with immunosuppressive therapy across all disease groups, there was an 86% response rate with 25 responders (11 PRs and 14 CRs) and 4 non-responders. This did correlate with higher BFU-E growth. Our results suggest BFU-E assays are a useful adjunct in the diagnosis and management of cytopenias in the setting of a normocellular or hypercellular bone marrows.

Colony-forming unit cell (CFU-C) assays at diagnosis: CFU-G/M cluster predicts overall survival in myelodysplastic syndrome patients independently of IPSS-R

“…Lower than normal frequencies of normal CFU-Cs and abnormal clusters of CFU-Cs are common in persons with MDS and were proposed as a diagnostic criterion [8-13]. We analyzed CFU-C quantity and quality in 365 consecutive, newly-diagnosed untreated subjects with MDS.…”

“…In vitro colony-forming unit cell (CFU-C) assays are usually-used to detect the quantitative and qualitative features of haematopoietic stem cells (HSCs) from normals and persons with diverse haematologic abnormalities including MDS [ 7 ]. Lower than normal frequencies of normal CFU-Cs and abnormal clusters of CFU-Cs are common in persons with MDS and were proposed as a diagnostic criterion [ 8 - 13 ]. We analyzed CFU-C quantity and quality in 365 consecutive, newly-diagnosed untreated subjects with MDS.…”

<p>Pathophysiologic Mechanisms And Management Of Large Granular Lymphocytic Leukemia Associated Pure Red Cell Aplasia</p>

“…The BFU-E assay can distinguish among MDS, systemic autoimmunity, LGLL and PRCA, which may be an important adjunct to the work-up of the undiagnosed cytopenias 65. Low BFU-E growth (<10 BFU-E/105 marrow mononuclear cells) is more consistent with a diagnosis of MDS and helps to exclude the diagnosis of PRCA, LGLL, or cytopenias from autoimmune diseases.…”

I Walk the Line: How to Tell MDS From Other Bone Marrow Failure Conditions

“…Burst forming units-erythroid (BFU-E) assays can also be used to exclude MDS in cases where dysplasia or markers of clonal hematopoiesis are equivocal. BFU-E growth above 40 colonies per 10 5 marrow mononuclear cells virtually eliminates MDS as an underlying etiology [42]. …”

“…The presence of LGL cells concurrently with MDS correlated with poor response to IST as compared to “pure” LGL [48]. Better response to IST was, however, observed in PRCA associated with an LGL clone [41, 42]. The identification of concurrent LGL cells, although important, may not warrant LGL-directed therapies.…”