Near haploid childhood acute lymphoblastic leukemia masked by hyperdiploidline: detection by fluorescence in situ hybridization

Near-haploid (< 30 chromosomes) acute lymphoblastic leukemia (ALL) is a rar e and unique subgroup of childhood common ALL associated with a very poor o utcome. It may be underdiagnosed when masked by a co-existing hyperdiploid line, which has to be distinguished from the common good-prognostic hyperdi ploid (> 50 chromosomes) ALL. We present three children in whom. by convent ional cytogenetics. near-haploid ALL was detected on relapse. Using interph ase FISH probes of chromosomes X, Y, 4, 12, and 21. we were able, in two ca ses, to trace the hidden near-haploid lines of approximately 5% and 20% of the cells, masked by hyperdiploid cells of approximately 80% and 70%. respe ctively: at relapse, the proportion was reversed, with predominant near-hap loid lines of over 80% and residual hyperdiploidy of less than 10%. The nea r-haploid lines consisted of 24 and 27 chromosomes. and always retained the second copy of chromosome 21 or its derivative, as detected in one of our patients by SKY. The hyperdiploid clones were the exact duplicates of the n ear-haploid ones and contained four and two copies of the chromosomes repre sented in two and one copies in the near-haploid stem line, respectively. U nlike the common hyperdiploid ALL. no trisomies were observed. The: patient s were all aged > 10 years. with WBC 0.7-30 X 10(9)/L. and a common ALL phe notype. They were treated with the ALL-BFM-95 protocol, medium risk group. and responded well to 8 days of steroid therapy, but relapsed early, within 11 months, and died a few months later. Interphase FISH technique is recom mended for the detection of cryptic near-haploid clones in the diagnostic s urvey of ALL. To assess the prognostic value of near-haploidy in the contex t of the ALL-BFM protocols, a larger cohort of patients is required. (C) 20 01 Elsevier Science Inc. All rights reserved.