A Complex Karyotype but Not Monosomy 7 Is an Independent Prognostic Factor in Advanced Childhood MDS.

Konference: 2007 49th ASH Annual Meeting - účast ČR

Kategorie: Nádory dětského a adolescentního věku

Téma: Postery

Číslo abstraktu: 2452

Autoři: Gohrin Gudrun; prof. Ing. Kyra Michalová, DrSc.; H.Berna Beverloo, PhD; MD David Betts; Jochen Harbott; Prof. Dr. Oskar A. Haas; Gitte Kerndrup; Laura Sainati; Eva Bergstraesser; Prof. MD Henrik Hasle; prof. MUDr. Jan Starý, DrSc.; Monika Trebo; MD Marry M. van den Heuvel-Eibrink, PhD; MD Marco Zecca; Alexandra Fischer, R.N.; Peter Noellke

To study the clinical significance of recurrent chromosome aberrations in childhood MDS, cytogenetic data of 394 consecutive children with refractory cytopenia (RC) (N=215), RAEB (N=141) and RAEB-T (N=38) analyzed in the regional cytogenetic reference centers and registered in the prospective study EWOG-MDS 98 between 1998 and 2005 were evaluated. At diagnosis, a karyotype could be defined in 279/394 patients (pts) (71%). No karyotype was obtained in 16% of pts with RC compared to 8% pts with RAEB and RAEB-t (p<0.001). Clonal chromosome aberrations were more common in pts with advanced MDS (RAEB and RAEB-T, 61%) compared to RC (29%), and in pts with secondary (69%) compared to primary MDS (36%) (p<0.001). Monosomy 7 was the most frequent aberration occurring with similar frequency in RC (47% of abnormal karyotypes) compared to advanced MDS (49%) and in primary (53%) compared to secondary (41%) MDS. In addition, aberrations typical for de novo AML such as aberrations involving 11q23 or 3q, t(6;9) and del(9q) were noted in morphologically and clinically unequivocal MDS cases. Recurrent aberrations of adult MDS like isolated del(5q), del(20q) and -Y were very uncommon indicating a different pathogenesis of these cases. In pts with advanced MDS, there was no significant difference in overall survival (OS) of pts with normal karyotype (44% 18) compared to pts with monosomy 7 (58% 19) and patients with other karyotypes (61% 22). However, pts with advanced MDS and a complex karyotype (defined by 3 chromosome aberrations, presence of structural aberrations and excluding clonal evolution of monosomy 7) had a shorter OS (16% 15, p<0.01). OS and event-free survival after hematopoietic stem cell transplantation (HSCT) in pts with complex karyotypes was inferior compared to that of pts with other cytogenetic aberrations (p=0.012 and 0.039, respectively). Within the group of pts with secondary MDS, complex karyotypes were found in MDS evolving from inherited bone marrow failure disorders or after radio-/ chemotherapy, but absent in familial MDS and cases evolving from acquired aplastic anemia. As shown in a multivariate Cox analysis, advanced MDS, secondary MDS, the presence of a complex karyotype and HSCT were identified as independent prognostic factors for OS. Thus, this study demonstrates the prognostic significance of cytogenetic findings in advanced childhood MDS independent of HSCT.

Abstract #2452 appears in Blood, Volume 110, issue 11, November 16, 2007

Keywords: Complex Aberrant Karyotype|MDS|Childhood

Disclosure: No relevant conflicts of interest to declare.

Sunday, December 9, 2007 6:00 PM

Session Info: Poster Session: Myelodysplastic Syndromes: Prognosis and Clinical Correlative Studies (6:00 p.m.-8:00 p.m.)

Datum přednesení příspěvku: 9. 12. 2007