Ten-year experiences on initial genetic examination in childhood acute lymphoblastic leukaemia in Hungary (1993-2002). Technical approaches and clinical implementation

Abstract

A nationwide study was started in 1993 to provide genetic diagnosis for all newly diagnosed childhood ALL cases in Hungary using cytogenetic examination, DNA-index determination, FISH (aneuploidy, ABL/BCR, TEL/AML1) and molecular genetic tests (ABL/BCR, MLL/AF4, TEL/AML1). Aim of the study was to assess the usefulness of different genetic methods, to study the frequency of various aberrations and their prognostic significance. Results were synthesized for genetic subgrouping of patients. To assess the prognostic value of genetic aberrations overall and event-free survival of genetic subgroups were compared using Kaplan-Meier method. Prognostic role of aberrations was investigated by multivariate analysis (Cox's regression) as well in comparison with other factors (age, sex, major congenital abnormalities, initial WBC, therapy, immunophenotype). Five hundred eighty-eight ALL cases were diagnosed between 1993-2002. Cytogenetic examination was performed in 537 (91%) (success rate 73%), DNA-index in 265 (45%), FISH in 74 (13%), TEL/AML1 RT-PCR in 219 (37%) cases producing genetic diagnosis in 457 patients (78%). Proportion of subgroups with good prognosis in prae-B-cell ALL was lower than expected: hyperdiploidB 18% (73/400), TEL/AML1+ 9% (36/400). Univariate analysis showed significantly better 5-year EFS in TEL/AML1+ (82%) and hyperdiploidB cases (78%) than in tetraploid (44%) or pseudodiploid (52%) subgroups. By multivariate analysis main negative prognostic factors were: congenital abnormalities, high WBC, delay in therapy, specific translocations.

Conclusion: Complementary use of each of genetic methods used is necessary for reliable genetic diagnosis according to the algorithm presented. Specific genetic alterations proved to be of prognostic significance.