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

Abstract

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 5 6; Testis: 4; CNS: 2) or combined hematopoietic and extramedullary relapses (n 5 2; BM 1 CNS: 1; BM 1 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 5 18) more frequently than isolated extramedullary (27.5%; n 5 8: Testis: 1; CNS: 7) or combined hematopoietic and extramedullary relapses (10.3%; CNS 1 BM: 3), with 24/29 (82.8%) of the relapses occurring on therapy. Relapses in hHDALL frequently involved EM sites (P 5 0.053). Presence of triple trisomy of 14,110,117 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 5 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. Am. J. Hematol. 83:34-40, 2008. V

High hyperdiploid childhood acute lymphoblastic leukemia

“…1), it is quite clear that most hypotriploid cases should be included. In practice, the upper limit has been variably defined as 61 (Forestier et al, 2008a), 65 (Moorman et al, 2003;Sharathkumar et al, 2008), and 67 Heerema et al, 2007). In most instances, no reasons are given for choosing a particular cutoff, but in a recent analysis of trisomies and tetrasomies at different modal numbers, Heerema et al (2007) concluded that the chromosomal patterns differed between cases with 51-67 chromosomes and those with >67 chromosomes.…”

High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

“…However, only a few clinical features have been shown to be associated with decreased EFS within the HeH group, namely age >10 years, male gender, and bone marrow fibrosis. 5,8,9 As regards genetic factors, it has been suggested that some karyotypic patterns and aberrations -low modal chromosome number, lack of certain trisomies, and the presence of various structural changes -confer a more dismal outcome, albeit with conflicting results in different studies. 2,4,5,7,[9][10][11][12][13] The prognostic impact of the "triple trisomies", i.e., concur-…”

Atypical chronic myeloid leukemia with isochromosome (X)(p10): A case report

“…A physical examination demonstrated no remarkable findings. A complete blood count exhibited the following results: WBC of 8.1x10 0%, myelocyte 0%, metamyelocyte 7%, neutrophil 56%, lymphocyte 19%, monocyte 18%), Hb level of 8.6 g/dl, a platelet count of 230x10 9 /l. The bone marrow morphology revealed 4% blasts, granulocyte proliferation with dysplasia and slight dysplasia in the megakaryocytic lineage identified by May-Giemsa staining with Giemsa and May-Grünwald solutions (Muto Pure Chemicals Co., Ltd., Tokyo, Japan), as presented in Fig.…”

“…A 40-year-old female was referred to the Tokyo Medical and Dental University Hospital (Tokyo, Japan), due to an annual medical checkup revealing slight leukocytosis and anemia, with a white blood cell count (WBC) of 12x10 9 /l (myelocyte, 2%; metamyelocyote, 6%) and a hemoglobin (Hb) level of 9.4 g/dl. A physical examination demonstrated no remarkable findings.…”

“…Initially, the patient did not receive any therapy, but exhibited a rapid increase in WBC to 43x10 9 /l in the 6 months following initial diagnosis, as demonstrated in Fig. 3.…”