PF283 A RETROSPECTIVE STUDY OF MYELOID LEUKAEMIA IN CHILDREN WITH DOWN SYNDROME IN IRELAND

Background: Children with trisomy 21 have several clinical complications such as a variety of dysmorphic features, congenital malformations and endocrine abnormalities for example. An important complication of Down Syndrome (DS) is that they may also develop leukaemia. Acute myeloid leukaemia (AML) is the type of haematological malignancy most commonly reported in this population. A subtype of AML called M7 leukaemia (as classified by FAB system) has an incidence nearly 200 times greater compared to children without DS. This is a type of leukaemia otherwise very rare in both adults and children. M7 leukaemia is often preceded by a transient neonatal pre‐leukaemic syndrome, called Transient Abnormal Myelopoiesis (TAM). TAM is unique as it has the ability to resolve spontaneously. However, 20–30% of these patients may develop M7 leukaemia over time. This is most likely to occur within the first 4 years of life. Aims: A retrospective national audit of all documented cases of childhood TAM and M7 leukaemia referred from 1990–2018 to the National Paediatric Hematology/Oncology Centre at Our Lady's Children's Hospital Crumlin (OLCHC) Ireland. We also aimed to compare our demographic and outcome findings with the recent medical literature and make recommendations for future research. Methods: All consecutive charts of the children with a diagnosis of M7 leukaemia treated at (OLCHC) between the years 1990 – 2019 were sourced from medical records. The hospital database and charts were reviewed and information including date and age of diagnosis of AML, comorbidities, previous history of TAM, treatment regime and outcome was noted. Cytogenetic information was obtained by accessing a dedicated database. Kaplan‐Meier survival curves were constructed. Results: Twenty‐seven patients with M7 leukaemia were treated in OLCHC. A prior neonatal diagnosis of TAM was described in 10 patients (37%). Patients had a low platelet count (<50 × 10 9  /L) at presentation. Nineteen patients (70%) are alive and well, in complete remission, at a median follow up of 11.4 years. Overall survival (OS) of this cohort has risen from 54% from those treated between the years 1990 – 2004 (n = 13) to 93% for those treated between the years 2005 – 2019 (n = 14). Summary/Conclusion: Overall an excellent outcome is observed in M7 leukaemia when treated with current poly‐chemotherapy protocols. In general children with DS have a much better response to the cytotoxic‐chemotherapy than constitutionally normal children. Our finding of a low platelet count at diagnosis is in accordance with the current knowledge that M7 leukaemia is a condition affecting platelet precursors. GATA‐1 is mutated universally in M7 leukaemia and therefore appears to be an interesting molecular target.