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- Karlsson, Lena, 1964, et al.
(författare)
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Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia
- 2017
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Ingår i: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 178:4, s. 592-602
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Tidskriftsartikel (refereegranskat)abstract
- Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y) was 39 +/- 4% for the whole group and 43 +/- 4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) +/- anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse >= 1 year from diagnosis, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61 +/- 5%. Four of 19 children (21%) survived without receiving SCT as part of relapse therapy. Our data show that intensive re-induction followed by SCT can give cure rates of 40% in children with relapsed AML.
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- Laursen, Anne Cathrine Lund, et al.
(författare)
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Trisomy 8 in pediatric acute myeloid leukemia : A NOPHO-AML study
- 2016
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 55:9, s. 719-726
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Tidskriftsartikel (refereegranskat)abstract
- Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0-18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO-AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined with other cytogenetic aberrations in 68 patients (11%) (+8 other) and in 18 patients (3%), it was the sole abnormality (+8 alone). Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with non-trisomy 8 patients. Trisomy 8 was favorable in patients of young age and with t(9;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 positive AML is a heterogeneous group and the majority of cases have additional cytogenetic aberrations. Patients with +8 alone differed from patients with +8 other and were associated with older age, FAB M2, and FLT3-ITD aberrations. There were no differences in survival despite the more frequent occurrence of FLT3-ITD in +8 alone.
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- Sandahl, Julie Damgaard, et al.
(författare)
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Ploidy and clinical characteristics of childhood acute myeloid leukemia : A NOPHO-AML study
- 2014
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 53:8, s. 667-675
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Tidskriftsartikel (refereegranskat)abstract
- We report the first large series (n=596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n=237) of all pediatric AML. Among patients with an abnormal karyotype, the MN 46 was most common (n=251; 56%) of which 36 (8%) were pseudodiploid with numerical aberrations, followed by MN 47 (n=80; 18%) and MN 43-45 (n=48; 8%). No cases had MN less than 43. Hyperdiploid AML with MN 48-65 comprised 11% of all cases and was associated with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex chromosomes. Inferior outcome was observed for hypodiploid cases (5-year event-free survival 40% and 5-year overall survival 40%) but did not reach statistical significance. Chromosomes were gained in a nonrandom pattern, where chromosomes 8, 21, 19, and 6 were the most commonly gained. In conclusion, based on MNs, two cytogenetic subgroups with characteristic clinical features are described; hypodiploidy found in 8% and associated with high median age, male sex, t(8;21)(q22;q22), and FAB M2 and possibly associated with inferior outcome (P=0.13), and hyperdiploidy with MN 48-65 in 11% associated with early onset, female sex, and AMKL.
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- Sandahl, Julie D., et al.
(författare)
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The applicability of the WHO classification in paediatric AML. A NOPHO-AML study
- 2015
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 169:6, s. 859-867
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Tidskriftsartikel (refereegranskat)abstract
- The World Health Organization (WHO) classification of myeloid leukaemia was revised in 2008. It incorporates newly recognized entities and emphasizes the pivotal role of cytogenetic abnormalities. The aim of this study was to evaluate the usability of the WHO classification when applied to a large population-based paediatric acute myeloid leukaemia (AML) cohort. We included children diagnosed with de novo AML, 0-18years of age from the Nordic countries and Hong Kong from 1993 to 2012. Data were retrieved from the Nordic Society for Paediatric Haematology and Oncology AML database and patients classified according to the WHO 2008 classification. A successful karyotype was available in 97% of the cases. AML with recurrent genetic abnormalities were present in 262 (41%) and 94 (15%) were classified as AML with myelodysplasia-related changes (AML-MDS). WHO classifies patients with monosomy 7 and del(7q) into one group. We found that -7 (n=14) had significantly poorer outcome than del(7q) (n=11); 5-year event-free survival 26% vs. 67%, (P=002), and 5-year overall survival 51% vs. 90%, (P=004). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n=280) (44%). In conclusion, the WHO classification allocated 15% to AML-MDS, 44% to NOS and grouped together entities with clearly different outcome, therefore limiting the applicability of the current WHO classification in children with AML.
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- Staffas, Anna, 1982, et al.
(författare)
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Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia.
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:22, s. 5905-5913
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Tidskriftsartikel (refereegranskat)abstract
- Mutation status of the FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in pediatric AML patients enrolled in the NOPHO 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients respectively. Presence of FLT3-ITD was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of pediatric AML patients and that determination of the BAALC gene expression level can add valuable information.
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