Prognostic value of clonal chromosomal abnormalities in patients with primary myelodysplastic syndromes.

Abstract

Chromosome analyses were carried out on bone marrow cells from 43 consecutive patients with primary myelodysplastic syndromes (MDS), classified according to the French-American-British (FAB) cooperative group criteria. The objective was to evaluate the prognostic value of clonal chromosomal abnormalities and of an excess of blasts for early death from acute nonlymphocytic leukemia (ANLL) and/or bone marrow failure (BMF). Patients were subdivided into two main groups: (1) refractory anemia without an excess of blasts (RAWEB), grouping patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS), and (2) refractory anemia with an excess of blasts (RAEB), grouping patients with refractory anemia with an excess of blasts (RAEB) and refractory anemia with an excess of blasts in transformation (RAEBt). There were 29 patients with RAWEB and 14 with RAEB. The median time of observation was 26 months for RAWEB and 12 months for RAEB. Ten RAWEB patients (34%) and 11 RAEB patients (78%) had clonal chromosomal abnormalities. Among the ten RAWEB patients with clonal abnormalities, one (10%) died from ANLL, while of 19 RAWEB patients with a normal karyotype, two (10%) died from ANLL or BMF. The median survival for patients with RAWEB and an abnormal karyotype was not reached. In contrast, eight of the 11 RAEB patients with clonal chromosomal abnormalities (74%) died from ANLL or BMF. The median survival in this sub-group was 7 months. By using a Cox proportional hazard regression analysis, it was determined that a karyotype abnormality was not a significant predictory of survival once the contribution of the RAWEB/RAEB variable was taken into account. Being in the RAEB group was associated with a relative risk of 10.6 of dying from ANLL or BMF (beta = 2.36, standard error (SE) = 0.68, P = .0001). We conclude that classifying patients according to an excess of blasts will lead to a better prediction of survival than determining karyotype abnormality.