Our case involved a 12-year-old male, who was diagnosed with relapsed AML 4 months after treatment. He was initially diagnosed with AML (French-American-British (FAB) classification: M0) 11 months prior to the relapse. Bone marrow aspiration (BMA) performed after the relapse revealed a blast frequency of 93.6% (FAB classification: M0). Peroxidase staining showed that the blasts did not contain any Auer bodies (Figure 1), and the blasts were positive for CD13 (29.8%), CD33 (99.8%), CD11b (98.4%), and CD34 (99.7%) and negative for cytoplasmic myeloperoxidase. Chromosomal analysis of the bone marrow revealed the following karyotype: 46, X, -Y, t(7; 12)(p15; p12), +10[4]/46, XY[7]. FLT3-ITD, a specific chimeric gene; chromosomal abnormalities (affecting chromosomes 5, 7, and 8); and central nervous system metastasis were not detected during the initial diagnosis or at relapse. After the initial diagnosis, the patient received five courses of chemotherapy (cytarabine, etoposide, and anthracycline) on the basis of his standard risk profile (the core-binding factor was not affected).
After the diagnosis of relapse, the patient received a course of FLAG-IDA-GO (30 mg/m2 fludarabine, 5 days; 2 g/m2 cytarabine, 5 days; 10 mg/m2 idarubicin, 1 day; and 3 mg/m2 gemtuzumab ozogamicin, 1 day) and one intrathecal injection (IT) [7]. Since a BMA examination performed after bone marrow recovery, that is, at 1 month after the first course of FLAG-IDA-GO indicated a non-CR (50.4%), we added a week of azacytidine. Thereafter, BMA showed a blast frequency of 87.8%, and chromosomal analysis revealed a karyotype of 46, X, -Y, t(7; 12)(p15; p13), +10[6]/46, XY[5]. Since in vitro drug sensitivity tests suggested that antimetabolic agents, such as clofarabine, and alkylating agents, such as cyclophosphamide and etoposide, would be effective, we then attempted combination chemotherapy involving clofarabine, cyclophosphamide, and etoposide (40 mg/m2 clofarabine, 5 days; 440 mg/m2 cyclophosphamide, 5 days; and 100 mg/m2 etoposide, 5 days) and one IT. After approximately 1 month, BMA indicated that CR and normal chromosomal findings had been achieved. Then, a second course of the same regimen (cyclophosphamide was administered at half the previous dose) was administered. After two courses of clofarabine had been administered, no severe clofarabine-associated adverse events were noted, except for febrile neutropenia, which was controlled with antimicrobial drugs (common terminology criteria for adverse events (CTCAE) grade 3); hepatotoxicity (increased aspartate aminotransferase levels (CTCAE grade 2) and increased alanine aminotransferase levels (CTCAE grade 2)); and bone marrow suppression (anemia and decreased neutrophil, white blood cell, and platelet counts (CTCAE grade 4 for all events)). After the second course of clofarabine, cyclophosphamide, and etoposide, the patient underwent allogeneic BMT from his father (completely matched for the human leukocyte antigen DNA type), which involved a preparatory regimen comprising total body irradiation (TBI) (12 Gy) and cyclophosphamide (60 mg/kg, 2 days). The BMT was successful and did not result in severe complications, and neutrophil engraftment was confirmed on day 29. Grade 4 acute graft-versus-host-disease (GVHD), involving intestinal symptoms, was temporarily observed and controlled with cyclosporin and prednisolone. Gradual amelioration of the acute GVHD was achieved through immunotherapy. BMA revealed a normocellular bone marrow without blasts, and hematological CR was maintained for 12 months after the BMT. Also, complete chimerism was detected using short-tandem-repeat analysis, and chromosomal analysis revealed a karyotype of 46, XY[20/20].