Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Abstract

Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.

Bone marrow histology and CD34 immunostaining in the prognostic evaluation of primary myelodysplastic syndromes

“…This result can be explained by the general experience that leukaemic transformationis not the only event heralding an unfavourable outcome in MDS patients (Lambertenghi et al, 1993). The prognostic significance of cytomorphology is considerably greater when FAB subtypes with an excess of blasts are grouped and compared to those without (Jacobs et al, 1986;Coiffier et al, 1987;Third MIC, 1988;Kitagawa et al, 1989;Sanz et al, 1989;Sanz & Sanz, 1992;Mufti, 1992;Hasle, 1994).…”

Hematologic and clinical features of patients with chromosome 5 monosomy or deletion (5q)

“…Cytogenetic abnormalities involving chromosome 5 (monosomy 5 or deletion of 5q) have been described in different hematologic diseases including myelodysplastic syndromes (MDS), de novo acute nonlymphoid leukemia (ANLL), and acute leukemia related to therapy (t-ANLL) of a primary neoplasia or to occupational exposure to potential leukemogenic agents [1][2][3][4][5][6][7][8][9][10][11]. In particular, a deletion of the long arm of chromosome 5 , del (5q), has been found to occur nonrandomly in humans; several case series with this specific anomaly have been published , and the topic has been extensively reviewed [17][18][19].…”

Trisomy 8 in a patient who responded to therapy with all‐trans‐retinoic acid and developed paroxysmal nocturnal haemoglobinuria

“…Trisomy 8 has also been reported in other myeloproliferative disorders including polycythaemia vera and myelofibrosis. In chronic myelogenous leukaemia the presence of þ8 has been associated with disease progression and is the commonest accompanying karyotypic aberration in acute promyelocytic leukaemia (Heim & Mitelman, 1986;Jacobs et al, 1986;Rowley, 1988). We report a case of MDS with trisomy 8 in a 18-year-old Greek girl who had a good therapeutic response to all-trans-retinoic acid and in the course of the disease developed paroxysmal nocturnal haemoglobinuria (PNH).…”