A prognostic impact of separation of refractory cytopenia with multilineage dysplasia and 5q− syndrome from refractory anemia in primary myelodysplastic syndrome

Abstract 

A prognostic impact of WHO classification of myelodysplastic syndrome (MDS) was studied in a group of 103 primary MDS patients with refractory anemia (RA) according to French–American–British (FAB) classification. Median survival of 37 patients with RA according to WHO criteria of 85.2 months was significantly different from that in both 37 patients with refractory cytopenia with multilineage dysplasia (RCMD) (47.0 months, P=0.002) and 29 patients with 5q− abnormality diagnosed by routine chromosome banding (36.2 months, P=0.0002). A more detailed karyotype analysis with fluorescent in situ hybridization (FISH) techniques confirmed 5q deletion as a sole cytogenetic abnormality in only 12 out of 29 patients, in 4 patients 5q− was associated with complex abnormalities involving 5q region, 13 patients had 5q deletion combined with further karyotype abberations outside 5q. No difference in median survival and estimated 3 years survival was observed between RA patients, patients with 5q− syndrome according to WHO morphology criteria and patients with 5q− as a single abnormality confirmed by FISH in contrast to patients with either additional 5q abberations or further karyotype changes not involving 5q. The same difference was also observed in time to 25% of patients evolving to acute myeloid leukemia (AML). Our study confirmed usefulness of separation of RCMD from RA. RCMD represents a poor prognostic subgroup of MDS clearly distinct from pure RA mainly due to short survival connected with progressive bone marrow failure and increased risk of leukemic transformation. We also suggest to define 5q− syndrome as primary MDS of FAB type RA with 5q deletion as a sole cytogenetic abnormality confirmed by FISH analysis. This definition enabled us to discriminate 5q− patients with favorable prognosis similar as in RA from those with poor outcome associated with 5q− combined with complex abnormalities involving either 5q or regions outside 5q.

Abbreviations: AML, acute myeloid leukemia, CFU-GM, colony forming unit granulocyte/macrophage, CMML, chronic myelomonocytic leukemia, FAB, French–American–British, FISH, fluorescent in situ hybridization, IPSS, International Prognostic Scoring System, ISCN, International System for Human Cytogenetics Nomenclature, MDS, myelodysplastic syndrome, RA, refractory anemia, RAEB, refractory anemia with excess of blasts, RAEB-T, refractory anemia with excess of blasts with transformation, RARS, refractory anemia with ringed sideroblasts, RCMD, refractory cytopenia with multilineage dysplasia, WHO, World Health Organization

Keywords: Refractory anemia, Refractory cytopenia with multilineage dysplasia, 5q− syndrome, Prognosis, WHO-classification, FAB-classification, Myelodysplastic syndrome