SP10 | ACUTE MYELOID LEUKEMIA SECONDARY TO MYELODYSPLASTIC NEOPLASIA WITH GERMLINE PREDISPOSITION IN X-LINKED SPINAL MUSCULAR ATROPHY TYPE 1: HYPOMETHYLANT THERAPY EFFICACY

Background: The Next-generation sequencing (NGS) in diagnostic workup of Myeloid Neoplasm(MN) has revealed that the Myelodysplastic Neoplasm (MDS) or Acute Myeloid Leukemia (AML) hereditary are more common than previously thought in adult patients (5-15%).Thus, MN with germline predisposition were included as a new dedicated entity in WHO 2022, but there are other rare disorders that lead to bone marrow failure not yet included. There may be new entities related to germline mutations, not yet been classified, that could predispose to MDS or to AML. We report a bone marrow failure syndrome (IBMFS) case, associated with X-linked spinal muscular atrophy type 1 or Kennedy Disease (MK),a rare motor neuron disease associated with a mutation of the androgen receptor gene on the long arm of the cr.X.This rare disease has developed sMDS then sAML. Clinical case:66-year-old Caucasian man with isolated persistent neutropenia came to our observation in March 2013.He was diagnosed with MK at 33y old. Bone marrow (BM) cytomorphology showed trilinear dysplasia with myeloblasts 4%(Fig.1).Karyotype (K) was 46,XY.MDS-MLD(WHO2008),R-IPSS and WPSS low was placed In February 2018, BM sample showed MB11% CD45+CD33+CD34+CD117+HLADR+.K was invariate.MDS-EB2 ELN 2017 was diagnosed.The pt underwent therapy with 5-azacitidine 75mg/m2 daily schedule for 7 (5+2) days at 4-week intervals receiving thirty-four cycles getting a partial response (PR). In December 2021AML-MRC ELN2017diagnosis was placed(Fig2).BM sample showed mieloblasts25%.K was 46,XY. It was performed NGS with evidence of ASXL1(VAF 37.1%);SRSF2(VAF 33.2%);EZH2(VAF6.1%).Pt received therapy with decitabine 20mg/m2/day for 5 every 28 days and venetoclax 100mg/day for 21 days a month. He performed four courses from February 2022 to May getting a complete response but with serious ematological and extra-ematological toxicity. The pt died in July 2022 for febrile neutropenia grade 5 CTCAE_v5.0. Conclusions:To date have not yet been described in the literature cases of MK associated with IBMFS.A new entity of MK-related germline mutations could be hypothesized that could predispose to MDS or to AML when associated with additional somatic mutations such as ASXL1.The study of the molecular biology profile of IBMFS-related MDS could be useful to stratify these diseases into dedicated risk categories and to better evaluate the predictive value of mutations such as ASXL1,TET2,DNMT3A when associated with X-linked genetic alterations.