Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest Oncology Group study

Abstract

The prognostic impact of trisomy 8, alone or with other clonal aberrations, was evaluated in 849 patients with previously untreated acute myeloid leukemia (AML) who were registered to 5 Southwest Oncology Group trials. At presentation, 108 (12.7%) patients had ؉8 in their karyotypes, including 43 (5.1%) patients with ؉8 as the sole aberration; 307 (36.2%) were normal, and 434 (51.1%) had other cytogenetic abnormalities. Patients with ؉8 were slightly older (P ‫؍‬ .033), had lower WBC (P ‫؍‬ .011), and had lower percentages of peripheral blasts (P ‫؍‬ .0004) than the patients without ؉8. Median survival time for all patients with ؉8 was 9.9 months (95% CI, 6.5-12.5), similar to that of "unfavorable" cytogenetics risk groups (8.3 months; 95% CI, 6.8-9.5.) Patients with ؉8 had significantly lower peripheral blasts (P ‫؍‬ .0002), WBC (P < .0001) counts, and decreased overall survival (OS) than patients with normal cytogenetics (9.9 months vs 15.4 months; P ‫؍‬ .006).However, survival of patients with ؉8 as the sole aberration did not differ significantly from those with normal cytogenetics (P ‫؍‬ .36). Thus, the trisomy 8 group as a whole had poor survival, which was largely attributable to worsened outcomes among patients whose trisomy 8 was associated with other unfavorable cytogenetic abnormalities. (Blood. 2002; 100:29-35)

Outcome after allogeneic transplantation for adult acute myeloid leukemia patients exhibiting isolated or associated trisomy 8 chromosomal abnormality: a survey on behalf of the ALWP of the EBMT

“…Also our results, with a median OS of 29 months, compared favorably with those observed with series reporting outcomes of þ 8 AML patients after mixed consolidation regimen (chemotherapy, autologous or allogeneic transplantation) in which median survival did not exceed 16 months. 1 Only four patients had t (15,17) and þ 8 in our series. We kept these four patients for the analyses, as the results did not change (for example, 5-year LFS was 43% excluding those four patients).…”

“…1 The prognostic effect of þ 8 as a sole chromosomal abnormality in AML remains debated and was found in the literature to be associated either with an intermediate or a poor prognosis. [1][2][3] The results of the Medical Research Council-AML10 trial has assigned AML patients with isolated þ 8 in the 'intermediate' cytogenetic abnormality risk group, showing a 3-year OS and relapse risk of 42 and 42%, respectively. This study suggested also a worsened outcome for these patients in comparison with other cytogenetic abnormality risk group categories within this heterogeneous 'intermediate' prognosis group.…”

“…4 Alternatively, patients with þ 8 occurring concomitantly with other cytogenetic aberrations seem to have the prognosis conferred by the accompanying cytogenetic abnormality, at least in the favorable prognosis group ((t(8;21), t(15;17), inv (16)) or when it is observed concomitantly to additional 11q23 aberrations. 1,5,6 Currently, data assessing specifically the role of allo-hematopoietic SCT (HSCT) in the setting of AML with þ 8 are still relatively sparse. 5,7 The aim of this multicenter retrospective analysis was to carry out a survey on overall outcomes after allo-HSCT of AML patients harboring þ 8 as a sole chromosomal abnormality or associated with other abnormalities.…”

Population-based demographic study of karyotypes in 1709 patients with adult Acute Myeloid Leukemia

“…The biological and clinical significance of trisomy 8 in AML remains unclear. 5,[25][26][27] In MDS, trisomy 8 is present only in progenitors and is lacking in long-term repopulating cells capable of engraftment in NOD-SCID mouse systems. In contrast del (5q) is present in the most primitive stem/progenitor cell population.…”

DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups

“…5 The intermediate prognosis group is heterogeneous and includes cases with normal karyotype (NK) (40-50% of AML) 6 and trisomy 8, among others. 7 Lately, several studies have focused on the importance of searching for specific receptor tyrosine kinase mutations, such as tandem duplications in FLT3 or mutations in NPM1, [8][9][10][11][12] as markers of prognosis in AML.…”