High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

Abstract

Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age of patients with "classic" high hyperdiploidy was lower than that of patients with translocation-positive high hyperdiploidy (P<0.001). Cases with triple trisomies (+4, +10, +17), comprising 50%, had higher modal numbers than the triple trisomy-negative cases (P<0.0001). The probabilities of event-free survival and overall survival were lower for those with white blood cell counts ≥50x10 9 /L (P=0.017/P=0.009), ≥5% bone marrow blasts at day 29 (P=0.001/0.002), and for high-risk patients (P<0.001/P=0.003), whereas event-free, but not overall, survival, was higher for cases with gains of chromosomes 4 (P<0.0001), 6 (P<0.003), 17 (P=0.010), 18 (P=0.049), and 22 (P=0.040), triple trisomies (P=0.002), and modal numbers >53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by a particularly favorable outcome.High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

High hyperdiploid acute lymphoblastic leukemia (ALL)—A 25‐year population‐based survey of the Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) Study Group

“…The former group concurs with a higher and the latter with a lower relapse risk. The fact that chromosomes 4, 5, 10, and 17 run alongside these two subentities qualifies them as discriminating factors and therefore also as potential prognostic indicators, a fact that has been repeatedly documented in previous studies …”

Patterns and frequencies of acquired and constitutional uniparental isodisomies in pediatric and adult B‐cell precursor acute lymphoblastic leukemia

“…If so, such cases may possibly display some distinct clinical features. Indeed, it has been reported that high hyperdiploid cases with high (>53/55) modal chromosome numbers have a superior outcome compared with those with lower modes (Raimondi et al, ; Moorman et al, ; Paulsson et al, ).…”

Cytogenetic Profile in 7209 Indian Patients with &lt;i&gt;de novo&lt;/i&gt; Acute Leukemia: A Single Centre Study from India

“…In addition to its importance in diagnosis, prognostic significance of cytogenetic subtypes has also been identified by various cooperative groups such as SWOG, MRC and CALGB. This has further led to establishment of ELN and NCCN guidelines that include cytogenetic risk groups: 1) favorable which includes t(8;21), inv (16) and t(15;17) with overall survival (OS) rates of 55% -65%; 2) intermediate with normal karyotype and; 3) adverse that frequently shows MDS-related abn (5), abn(7), inv(3), -17/abn(17p) and monosomal and/or complex karyotype with OS rates of 5% -14% [2] [4]- [10].…”