Population-based study of the pattern of molecular markers of minimal residual disease in childhood and adult acute lymphoblastic leukemia: An assessment of the practical difficulty of representative sampling for trial purposes

Background. The prevalence, in unselected patients with acute lymphoblastic leukaemia (ALL), of clonal rearrangements suitable for minimal residual di sease (MRD) studies has not been formally investigated. Procedure. This was a prospective? demographic study of the frequency of molecular markers of MRD in all patients with ALL presenting over 5 years within the Northern He alth Region of England (population 3.1 million). Presentation marrow sample s were examined to detect informative markers. Results. One hundred twenty- four children (age <15 years) developed non-Burkitt ALL. No material was av ailable for study in 21. Eighty-six had clonal gene rearrangements (BCR/ABL , immunoglobulin heavy chain (ICH) and/or T cell receptor (TCR) gene rearra ngements). All entered remission; 84 (68% of the original cohort) survived to become eligible for MRD studies. One hundred sixteen adults developed AL L, of whom 48 were not studied due to insufficient cellular material in the bone marrow aspirate or to logistical problems in central referral of samp les from ether hospitals. Material from elderly adults (age >55 years) was less likely to be sent for analysis, 36% vs. 59% (P = 0.024). Thirty-eight had BCR/ABL and/or IGH/TCR gene rearrangements. Thirty-one (27% of the orig inal cohort) entered remission and became eligible for MRD studies. informa tive gene rearrangements were more common in children than adults (83% vs. 63%, P < 0.003). Conclusions. The results reveal substantial potential, uni ntentional, selection bias. Large-scale multicentre studies of MRD in child ren may well produce clinically relevant and representative data. Those who mount similar studies in adults should not assume they will be similarly r epresentative or as successful in accrual of material. Med. Pediatr. Oncol. 34:106-110, 2000. (C) 2000 Wiley-Liss Inc.