Hyperdiploidy in Childhood AML Associated with Low Age and AML-M7. A NOPHO-AML Study and Literature Review,
Authors: Sandahl Julie Damgaard , Abrahamsson Jonas , Heldrup Jesper , Jahnukainen Kirsi , Jonsson Olafur G , Lausen Birgitte , Palle Josefine , Zeller Bernward , Forestier Erik , Kjeldsen Eigil , Hasle Henrik 
Published: October 2019

Abstract
Abstract 3529

Introduction:
High hyperdiploidy (51–67 chromosomes) is one of the most common cytogenetic abnormality patterns in childhood B-cell precursor acute lymphoblastic leukemia (ALL) and the clinical and cytogenetic features are well characterized. High hyperdiploidy in pediatric acute myeloid leukemia (AML), however, is a rare cytogenetic finding. It is most often categorized as a complex karyotype, which is considered associated with an unfavorable outcome. The group of complex karyotypes is heterogeneous and the significance of multiple additional chromosomes with or without structural abnormalities among the pediatric hyperdiploid AML patients is relatively unknown. Current knowledge in this field is based on small adult series or case reports. In this descriptive study we describe the clinical - and cytogenetic features in childhood hyperdiploid AML with a modal chromosome number at 50 or more. We report a series of 29 children from the Nordic Countries diagnosed with high hyperdiploid (50+) AML along with 105 cases identified from the literature.

Material and Method:
Children age 0–18 years diagnosed with AML and treated according to the NOPHO –AML-93 or 2004 protocols from 1993 to 2010 and with a karyotype including at least one clone with a modal number of 50 or more were identified in the NOPHO-AML database. They were compared to all non-hyperdiploid AML children diagnosed in the Nordic countries and treated according to same NOPHO protocols. Furthermore we conducted a literature study searching for hyperdiploid childhood AML (50+) cases using the Mitelman, PubMed, and Scopus databases. The 105 patients from the literature study were compared to the hyperdiploid NOPHO-AML patients. The total cohort of 134 hyperdiploid cases were used to characterize hyperdiploid AML in children

Results:
Clinical: The 29 hyperdiploid patients from the population based NOPHO-AML database constituted 6% of all childhood AML cases. Compared to all other NOPHO-AML patients, the hyperdiploid had similar sex distribution (45% boys) but were younger, median age 3 years vs. 6.5, had a lower WBC, median WBC 9.5 vs. 19.0, and an excess of M7 28% vs. 6%, (p<0.01). Survival was similar, 5-year EFS in both groups 50%, OS 59% vs. 67%.The 105 cases retrieved from the literature were published in the period from 1978–2010. The cases from the literature showed similar age, WBC and FAB M7 pattern as the NOPHO patients.
Cytogenetics: In the total hyperdiploid cohort 100 (75%) were near diploid (modal number 50–57), 8 (6%) were near triploid (58–80), 24 (18%) were near tetraploid (81–103). Only 2 cases were pentaploid (modal number of 117 and 127). Modal number 50 (25%), 51 (19%) and 52 (13%) were most common. The most frequently gained chromosomes were chromosome 8 (78%), chromosome 19 (67%), chromosome 6 (63%) and chromosome 21(58%). (figure 1) Survival data were available for 94 patients: 29 from the NOPHO and 65 from the literature. All chromosomes were represented as additional chromosomes and they were all analyzed for prognostic significance. Additional chromosome 8 indicated favorable outcome (log rank 0.09), whereas additional chromosome 21 was unfavorable (log rank <0.001). Additional chromosome 6 and 20 suggested unfavorable outcome (log rank 0.11). Structural abnormalities were found in 85% and associated with a non-significant inferior survival (5-year OS 33% vs. 53%, log rank 0.21).

Conclusion:
Hyperdiploidy (50+) is found in 6% of childhood AML and is associated with young age, low WBC, and AML M7. Most patients had a modal number of 50, 51 and 52, and the most frequently gained chromosomes were 6, 8,19, and 21; a distinctively different pattern from the high-hyperdiploid ALL. Overall survival in the hyperdiploid patients seems similar to the non-hyperdiploids. Gain of chromosome 8 was associated with favorable outcome whereas gain of chromosome 21 was associated with an inferior outcome.

Disclosures:
Hasle: Pfizer: Research Funding.