Acute Lymphoblastic Leukemia in Children with Associated Genetic Conditions Other Than Down Syndrome. The AIEOP Experience.

Background and Objectives. Constitutional molecular defects are known to play a role in oncogenesis, as shown by the increased incidence of embryonic cancers in children with Beckwith-Wiedemann syndrome or of leukemia in children with Down syndrome. The association between acute lymphoblastic leukemia (ALL) and genetic diseases other than Down syndrome has been less widely investigated. The aim of this study was to address this issue in a large series of childhood ALL patients prospectively treated in the AIEOP-ALL studies.

Design and Methods. We retrospectively reviewed the data-bases of AIEOP studies ALL-79, 82, 87, 88, 91, 95, and 2000 to identify all patients in whom an associated genetic disease, other than DS, had been reported.

Results. Out of the total of 6.695 patients, 42 (0.62%) were reported to have an associated genetic condition, including b-thalassemia (n=10), ataxia-telangiectasia (n=5), neurofibromatosis (n=3), Sotos syndrome (n=2) and a number of other individual conditions. Complete remission was achieved after induction therapy in 37 patients (1 died, 2 were resistant, 2 were not evaluable), of whom 10 had an adverse event, either death during remission (n=1), leukemia relapse (n=8), or went off-study (n=1). In the two largest groups, while patients with b-thalassemia had an outcome comparable to that of the general population, those with ataxia-telangiectasia, all with T-cell ALL, had a higher frequency of adverse events.

Interpretations and Conclusions. In the AIEOP experience, 0.62% of the patients enrolled in the childhood ALL studies have an associated genetic disorder; due to the reasonable risk of underestimation, this should be taken as a minimal rate. Although such patients should have access to contemporary ALL-directed therapy, those with ataxia-telangiectasia are more likely to deserve treatment modifications. Childhood leukemia specialists should pay special attention for screening of clinical signs or symptoms, as well as personal and family history, which may be relevant for identification of a possible associated condition. Study of such associations may provide additional clues for studying leukemogenesis in humans. Given the high probability of cure, for most patients leukemia will be only one part of their medical history. Thus, a correct diagnosis of the underlying genetic condition may be particularly useful for the patients and their families in order to tailor the future medical follow-up also during adulthood.