Therapy Related Acute Myeloid Leukemia in Two Patients with Ewing Sarcoma

Summary: Ewing Sarcoma is a rare type of bone and soft tissue cancer in children and young adults. Five-year survival rates in localized Ewing Sarcoma after chemotherapy, surgery, and/or radiation therapy is estimated ~79%. However, these patients may be at risk of developing therapy-related neoplasms due to the extensive cytotoxic treatments. Here, we report two pediatric patients with therapy-related acute myeloid leukemia (t-AML) post chemotherapy for Ewing Sarcoma. Patient 1 is a 14-year-old female with a history of localized Ewing sarcoma of the right distal humerus status 1.5-month post chemotherapy. The patient presented with back pain, nausea, and elevated WBC. Bone marrow aspirate was received at the UPMC Cytogenetics Laboratories for evaluation. Fluorescence in-situ hybridization (FISH) using a breakapart probe was positive for the KMT2A gene rearrangement. Karyotype was 46,XX,t(9;11)(p22;q23)[20], and microarray analysis was normal due to the balanced nature of KMT2A rearrangement. The patient deceased shortly after the initial presentation and clinical diagnosis of AML. Patient 2 is a 14-year-old male with recurrent Ewing sarcoma status 2-years post chemotherapy, presenting with cough and fever. Treatment started due to metastatic disease involving both lungs and the mediastinum. Two months later, Patient 2 presented with pancytopenia. FISH analysis was positive for the KMT2A gene rearrangement. Chromosome analysis revealed karyotypes of 46,XY,inv(11)(q21q23),add(18)(p11.2)[3]/46,XY[17] and 46,XY,inv(11)(q21q23)[11]/92,idemx2[2]/46,XY[7], for the right and left bone marrow specimens, respectively. Bilateral aspirates had normal microarray findings. Patient was diagnosed with t-AML. A subsequent sample two months after treatment has detected the persistence of the abnormal clone. Patients receiving chemotherapy for Ewing sarcoma appear to have an increased risk for t-AML. KMT2A gene rearrangement portends a poor prognosis in t-AML, and may represent with translocation, inversion, partial tandem duplication, or amplification. Comprehensive cytogenetic analysis (karyotype, FISH and microarray) is required to ensure detection of various KMT2A rearrangement types. Mahmoud Aarabi