A population-based cytogenetic study of adults with acute lymphoblastic leukemia

Abstract

Chromosomal abnormalities are increasingly used to risk stratify adults with acute lymphoblastic leukemia. Published data describing the age-specific incidence of chromosomal abnormalities and their prognostic relevance are largely derived from clinical trials. Trials frequently have age restrictions and low recruitment rates. Thus we investigated these factors in a population-based cohort of 349 patients diagnosed during the course of 19 years in the northern part of England. The incidence of most chromosomal abnormalities varied significantly with age.The incidence of t(9;22)(q34;q11) increased in each successive decade, up to 24% among 40-to 49-year-old subjects. Thereafter the incidence reached a plateau. t(4;11)(q21;q23) and t(1;19)(q23; p13) were a rare occurrence among patients older than 60 years of age. In contrast, the frequency of t(8;14)(q24;q32) and t(14;18)(q32;q21) increased with age. High hyperdiploidy occurred in 13% of patients younger than 20 years of age but in only 5% of older patients. The incidence of low hypodiploidy/near-triploidy and complex karyotype increased with age from 4% (15-29 years) to 16% (> 60 years). Overall survival varied significantly by age and cytogenetics. Older patients and those with t(9;22), t(4;11), low hypodiploidy/near-triploidy, or complex karyotype had a significantly inferior outcome. These population-based results demonstrate the cytogenetic heterogeneity of adult acute lymphoblastic leukemia. These data will inform the delivery of routine clinical services and the design of new age-focused clinical trials. (Blood. 2010;115:206-214)

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…We did not find any statistical association of outcomes after UCBT with cytogenetic risk stratification according to Moorman et al 17 , SWOG 34 (data not shown) neither when analyzing specifically the impact of Philadelphia chromosome. Despite remaining a major risk factor in ALL, 2,35 outcomes of Philadelphia-positive patients have markedly improved after the introduction of tyrosine kinase inhibitors in treatment protocols, before and after allo-SCT.…”

Genetic Studies in Acute Lymphoblastic Leukemia, from Diagnosis to Optimal Patient’s Treatment

“…Ph positivity is more often present in adult patients and the incidence increases with the age from 20% in 30 years to 39% in over 60 years (Moorman A.V., 2010). In these cases, targeted therapy using tyrosine kinase inhibitors such as imatinib or dasatinib is combined with chemotherapy both in young and elderly patients (Foa et al, 2011;Ravandi et al, 2010;Laport et al, 2008;Tanguy-Schmidt et al, 2009).…”

Pathophysiology of Acute Lymphoblastic Leukemia

“…The hypodiploidy and complex karyotype (presence of more than 2 chromosomal abnormalities) also increase with age, from 4% in the range of 15 to 29 years of age and 16% older than 60 years. (Moorman et al, 2010) ii.…”

“…( Other chromosomal abnormalities associated with age are the t(4;11)(q21;q23) and t(1;19) (q23;p13), that are rare in patients older than 60 years of age, but on the other way t(8;14) (q24;q32) and t(14;18)(q32;q21) increases with age. (Moorman et al, 2010) The translocation t(4;11)(q21;q23) leads to the formation of the MLL-AF4 fusion gene, and is responsible for more than 50% of ALL cases in children younger than 6 months in 10-20% of older infants, in approximately 2% of children and only 10% of adults with de novo ALL. Chromosomal abnormality in adults with ALL is considered to be of high risk.…”

“…(Liang et al, 2010) Recently, it was reported that the incidence of chromosomal alterations is associated with age. (Moorman et al, 2010) In fact, age is a determining factor in the prognosis and treatment outcome for patients with ALL. In long term survival, the rates are close to 80% in children under 5 years of age, but will decrease to 50% or 60% in adolescents and young adults, and approximately 30% in adults of 45 to 54 years, but rarely exceed 15% in older adults.…”