Can We Refine Diagnostic Criteria for Refractory Anemia with Ring Sideroblasts Associated with Marked Thrombocytosis (RARST)?
Heesun J Rogers, Valeria Visconte, Ramon V Tiu, Jaroslaw P Maciejewski, Eric D Hsi. Cleveland Clinic, Cleveland, OH
Background: RARST is considered as a provisional entity within myelodysplastic/myeloproliferative neoplasm (MDS/MPN), unclassifiable. Its diagnostic criteria include RA with erythroid dysplasia, >15% of erythroid precursors, <5% blasts and megakaryocytic hyperplasia with atypical forms, and platelet count >450 ×109/L. RARST shows a mutational spectrum overlapping with other myeloid neoplasms. JAK2 mutation is relatively common in RARST and confers favorable prognosis. TET2 mutation is noted in a subset of RARST and may constitute an early marker of RARST evolution. The clinicopathologic and molecular features in RARST are not well defined. We studied a series of RARST cases in order to determine whether diagnostic criteria could be refined.
Design: 32 cases of RARST (17 women, 15 men; median age 75 years) meeting WHO criteria were studied. The cases were divided as 1) MPN group with at least one of followings; splenomegaly, leukoerythroblastosis, teardrop cells, unilineage or no dysplasia or myelofibrosis(MF); 2) MDS group with dysplasia in 2-3 lineages and no MPN features; 3) mixed MDS and MPN group. Clinical and laboratory data, morphology in blood and BM, reticulin and pSTAT5 stain, karyotype, JAK2 and TET2 mutation were reviewed. Kaplan-Meier survival analysis with log rank test was used for overall survival (OS).
Results: Median platelet count, WBC, Hb, MCV and RS were 613×109/L, 9.6×109/L, 9.9g/dL, 102fL and 50%, respectively in the entire group. The median survival was 42 months (range 5-116). JAK2 and TET2 mutations were found in 22% and 29% of cases and were not associated with OS (p=0.26, p=0.88). Subgrouping resulted in 6 MDS type, 8 MPN type and 18 mixed type cases with no difference in OS (p=0.07). Compared to the mixed group, the MPN group was more likely to harbor a JAK2 mutation (75% and 17% p=0.002, chi square). Interestingly, compared to MPN and mixed cases, the MDS group had no JAK2 or TET2 mutations, shorter OS (26 months, p=0.04) and lower WBC (p=0.01). MDS type cases never progressed to a typical MPN. When excluding MDS type cases, RARST has mutation rates of 35% for JAK2 and 36% for TET2.
Conclusions: RARST is a heterogeneous disease that appears to contain a MDS-like subgroup that lacks TET2 or JAK2 mutation, and has shorter survival and lower WBC compared to cases with some degree of MPN-like features. Refining the criteria to exclude the MDS-like subgroup from RARST may result in a more biologically and clinically homogenous entity.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 231, Wednesday Morning