Children with hyperdiploid but not triple trisomy (+4, +10, +17) acute lymphoblastic leukemia have an increased incidence of extramedullar relapse on current therapies: A single institution experience

To evaluate the outcome of children with high hyperdiploid acute lymphoblastic leukemia (hHDALL) treated at the author's institution. One hundred thirty-five consecutive children with B-precursor ALL were diagnosed between 1991 and 2002: 38 (28.1%) hHDALL and 97 (71.9%) non-hHDALL. In the hHDALL group, 11/38 (28.9%) relapsed at a median interval of 2.8 years (range: 0.8-5.0 years) with 9/11 relapses occurring at the end or after the completion of therapy. Three (27.3%) relapses were isolated hematopoietic (BM), while eight (72.7%) were either isolated extramedullary (EM) relapses (n = 6; Testis: 4; CNS: 2) or combined hematopoietic and extramedullary relapses (n = 2; BM + CNS: 1; BM + Testis: 1). For the non-hHDALL group, 29/97 (29.9%) relapsed. Unlike the hHDALL group, the non-hHDALL group experienced hematopoietic relapses (62%; n = 18) more frequently than isolated extramedullary (27.5%; n = 8: Testis: 1; CNS: 7) or combined hematopoietic and extramedullary relapses (10.3%; CNS + BM: 3), with 24/29 (82.8%) of the relapses occurring on therapy. Relapses in hHDALL frequently involved EM sites (P = 0.053). Presence of triple trisomy of +4, +10, +17 at diagnosis had a protective effect against relapse (P < 0.05). Five-year EFS for the hHDALL and non-hHDALL patients was similar, 70.5 ± 7.5% and 66.4 ± 4.9%, respectively. Five-year OS for the hHDALL patients was significantly higher than for the non-hHDALL patients, 92 ± 4.5% vs. 74.1 ± 4.5%, P = 0.038. Biologically significant differences exist between relapse patterns of hHDALL and non-hHDALL cases related to relapse sites and time periods when relapses occur. hDALL relapses continue to be chemo-sensitive.