t(8;21) Positive AML with Favorable Clinical Characteristics, in a Child with Ependymoma after Combined Treatment with Neuroaxis Irradiation and Topoisomerase II Inhibitors.

The extensive use of etoposide has been implicated in the development of secondary acute myelogenous leukemia (AML) with unfavorable prognostic characteristics and most often involvement of the 11q23 locus. The case herein being presented exhibits favorable characteristics and poses the question whether it represents a secondary malignancy or a second primary event. A five year old boy was diagnosed with a mass of the posterior fossa representing anaplastic ependymoma of the brain stem (medulla oblongata) without CNS nor distant metastases. After partial resection of the tumor, the patient received 53 Gy to the tumor bed and 30 Gy to the neuroaxis followed by temozolamide p.o. for 4 cycles. Following this treatment, symptoms improved, he was ambulatory and back to school. Two years later he relapsed with unresectable tumor and received etoposide (VP-16) at 100 mg/m²/day for 21 days of 28 cycles, with a palliative intent. The treatment proved efficacious to him and he continued to receive VP-16 for 3 years in total. Six years after initial diagnosis and 3 years on VP-16, he developed ecchymoses, with thrombocytopenia (PLT: 15 k/uL) and leukocytosis (WBC: 25.8 k/uL). Bone marrow evaluation revealed infiltration with AML M2 blasts (>80%), MPO+ (93%), CD 34+ (58%), CD15+ (19%), CD71+ (33%), CD38+ (87%), CD33+ (47%) and CD123+ (52%), karyotype with detection of t(8;21). Bone marrow RT-PCR confirmed the presence of AML1-ETO hybrid gene, the absence of the MLL-AF4 product, and the absence of 11q23 involvement. Results were also confirmed by FISH technique. The patient was started on chemotherapy according to the AML-BFM 98 protocol. Disease remission was rapidly achieved (day +15 BM with no blasts) and treatment schedule was prompt, for the first 4 months of treatment. Severe, long-lasting marrow aplasia followed and pulmonary Aspergillosis was evident (compatible findings on CT and detection of Aspergillus specific proteins in the plasma by PCR), requiring assisted ventilation. However the patient succumbed 5 months following the diagnosis of AML. Childhood ependymomas have a dismal prognosis despite intensive treatment. This child exhibited a similarly good treatment response either to the ependymoma or to the later evolved AML. This AML1-ETO positive AML either representing a second primary malignancy or a rare type of secondary, therapy induced leukemia, is not a common and well described event and it certainly did not present, in our case, the usual dismal course of a secondary AML. Of importance our patient achieved and remained in remission with minimal treatment, for over 5 months, verifying the good prognosis of AML1-ETO positive AML either as a primary or a secondary event.