Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia; A matched-pair analysis

Purpose: The translocation t(9;22)(q34;q11), known as Philadelphia chromosome (Ph-1) or its molecular equivalent the expression of BCR-ABL-mRNA, is one of the most striking and well-characterized cytogenetic abnormalities in leukemia, Although investigated for more than 30 years, it remains unclear whether the Ph-1 is an independent risk factor for outcome of leukemia or not, Methods: A matched-pair analysis was performed within a homogeneous group of patients, which consisted of children who presented with a first relapse of acute lymphoblastic leukemia (ALL) who were treated according to ALL relapse trials (ALL-REZ BFM) protocols, A total of 307 patients were eligible for this analysis: 30 positive and 277 negative for Ph-1. Positive patients were marched exactly for time point of relapse (on [during] or off [after cessation of] front-line therapy), site, and immunophenotype, and as close as possible for duration of first remission, peripheral blast-cell count, WBC count, and year of relapse diagnosis, Results: The probability of event-free survival is 0.46 at 5 years for negative and 0.11 for positive patients, respectively (P = .0006). Multivariate analysis showed risk ratios of 4.229 for relapse on therapy, 3.561 for Ph-1 and/or expression of BCR-ABL- mRNA, 1.691 for high peripheral blast-cell count, and 0.232 for bone marrow transplantation. Conclusion: It was shown that the Ph-1 is indeed an independent risk factor in childhood relapsed ALL. There are striking similarities between these patients and children at initial diagnosis, as well as adult patients, Therefore, it is highly suggestive that the Ph-1 is also an independent risk factor under all of these circumstances. (C) 1997 by American Society of Clinical Oncology.