Idiopathic Cytopenia of Undetermined Significance (ICUS): The Importance of Clinical, Morphologic and Cytogenetic (CG) Correlation
CA Hanson, DK Durnick, JD Hoyer, JM Hodnefield, RP Ketterling, DP Steensma. Mayo Clinic, Rochester, MN
Background: ICUS is a provisional diagnostic category for patients who may be in pre-MDS clinical phase. Criteria include: persistent cytopenia (≥6mo); no morphologic features of MDS; normal CG studies; and exclusion of known causes of cytopenias including possible therapy-related MDS. In the 2008 WHO classification, patients with normal bone marrow (BM) morphology but with certain abnormal karyotypes are considered as MDS, unclassifiable.
Design: 2899 Mayo Clinic patients had BM studies for cytopenias from 1996-2008. 2110 were diagnosed as having MDS; 535 were excluded due to concurrent lymphoid / plasma cell malignancies, chemotherapy for any reason, or <18 y.o. 182 patients had >1 cytopenia, normal BM morphology, and normal CG studies; 62 had >1 cytopenia, normal BM morphology, but had an abnormal CG karyotype. The latter 244 patients were the basis for this study.
Results: 90/182 patients with normal CG had >6mo. follow-up. 80/90 patients were found to have a non-MDS etiology for the cytopenias including organ-based disease, immune causes, non-heme malignancies, etc. None developed MDS/AML during follow-up (6-148 mo; med=56). The remaining 10 patients met criteria for ICUS. 6/10 progressed to MDS and 4 have not; time to progression (TTP) to MDS was 14-125 mo (med=37). 39/62 patients with normal BM but abnormal CG had >6 mo follow-up. 8/39 with abnormal CG have progressed to MDS and 1 to AML; TTP was 5-54 mo (med=16). Cytopenias resolved in 16/39 and 14/39 have persistent cytopenias without progression to MDS or AML (6-158 mo; med=29). In these latter 30 patients, karyotype abnormalities vary: 5q-, -7, +8, 20q-, and others. Repeat studies in 8 patients showed: 3 now having a normal karyotype, 1 with a new abnormality, and 4 with a persistent clone.
Conclusions: ICUS is a valid concept for patients with unexplained cytopenias, normal BM, and normal CG but requires a comprehensive clinical assessment. ICUS is uncommon with only 10 cases identified over 12 yrs and 60% evolved to MDS over 1-10 yrs. However, our results do not support the automatic inclusion of patients with normal BM but abnormal CG as MDS. A minority of these patients do progress to MDS or AML but some patients with abnormal CG will see resolution of their cytopenias or other non-MDS cytopenic etiologies will be identified. The findings from our study point out the important role of BM morphologic studies in evaluating cytopenias and the value of correlating clinical, morphologic, and genetic findings in these patients.
Tuesday, March 23, 2010 8:45 AM
Platform Session: Section B, Tuesday Morning