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.

Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of four cases

“…In myelofibrosis, the incidence of trisomy 8 was one in 15 cases of karyotype abnormalities in 47 patients (2%) at the time of diagnosis (15). The incidence of trisomy 8 was 54 of 713 cases (7.6%) in AML (16) and nine cases of 49 cases (18.4%) in MDS (17). The association of trisomy 8 in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and chronic myeloproliferative disorder (CMPD) suggests that progression of the disease may have increased the incidence of trisomy 8 and development of leukemic transformation.…”

High-dose chemotherapy in high-risk myelodysplastic syndrome

“…In patients with HR MDS, median survival among larger study groups was reported to range between 8 and 18 months for RAEB and 4 and 15 months for RAEB‐t 3–5, 8. Although several more advanced prognostic models were subsequently developed based on multivariate analysis of variables,2–10 the FAB classification provided a basis for the first risk‐oriented management strategies.…”

Myelodysplastische Syndrome: Ein Überblick

“…Die fünf Untergruppen des MDS nach der FAB-Klassifikation (2) lassen sich in zwei prognostisch unterschiedliche Krankheitsbilder aufteilen. Die FAB Subtypen mit geringem Blastenanteil im Knochenmark « 5 %) überleben im Median über 60 Monate (8,14) und gehen selten in eine akute Leukämie über (15 %) (übersicht bei 12), während die Subtypen mit höherem Blastenanteil (~5 %-30 %) im Median nur zwischen 5 und 25 Monate überleben und häufig eine Entwicklung zur akuten Leukämie aufweisen (bis 60 %) (12). Andere prognostische Faktoren wie Blastenanteil, Dysplasie von zwei oder drei Zellreihen oder Anteil der Mikromegakaryozyten sind nicht unabhängig von der oben genannten Einteilung nach der FAB-Klassifikation.…”

“…Andere prognostische Faktoren wie Blastenanteil, Dysplasie von zwei oder drei Zellreihen oder Anteil der Mikromegakaryozyten sind nicht unabhängig von der oben genannten Einteilung nach der FAB-Klassifikation. Nach Jakobs et al (14) trifft diese Aussage auch für die von Tricot et al (19) beschriebene Clusterbildung im Knochenmark zu, die zwar auf eine ungünstige Prognose hinweist, aber vorwiegend bei den Subtypen CMML, RAEB und RAEB-T vorkommt.…”