Blood consult Blood consult: acute myeloid leukemia and the t(8;21)(q22;22) Jae H. Park, 1 Cyrus V. Hedvat, 2 and Martin S. Tallman 1 1 Leukemia Service, Department of Medicine, and 2 Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY Case presentation A 47-year-old man presented to his primary care physician with increasing fatigue and spontaneous bruising. Laboratory evaluation revealed a white blood cell count (WBC) of 80 000/mm 3 , hemato- crit of 25.6%, platelet count of 9000/mm 3 , and lactic dehydroge- nase of 1075 U/L (reference range 110-210 U/L). He was immedi- ately transferred to a local hospital. The peripheral blood smear showed predominantly myeloblasts with high nuclear:cytoplasm ratio, fine chromatin, prominent nucleoli, and numerous cells with an Auer rod. The platelets were significantly decreased in number and no nucleated red blood cells were identified. The bone marrow aspirate and biopsy revealed sheets of large blasts with fine chromatin and numerous Auer rods without normal hematopoiesis (Figure 1A). Immunophenotypic analysis of the blast population showed expression of CD13, CD19, CD33, CD34, CD117, and HLA-DR with partial expression of CD11b and CD33. The cytogenetic analysis demonstrated t(8;21)(q22;q22) in 20 of 20 metaphases examined. Molecular studies did not identify a FLT3 or NPM1 mutation. These findings were consistent with a diagnosis of core binding factor acute myeloid leukemia (CBF AML). The patient received induction chemotherapy consisting of daunorubicin 90 mg/m 2 for 3 days and cytarabine at 200 mg/m 2 by continuous infusion for 7 days. A bone marrow aspirate and biopsy at day 14 after the beginning of induction revealed 10% cellularity with 7% residual blasts. On day 16 he subsequently received reinduction chemotherapy consisting of daunorubicin 45 mg/m 2 for 3 days and cytarabine 100 mg/m 2 by continuous infusion for 7 days. A repeat bone marrow aspirate and biopsy at day 14 after the reinduction chemotherapy showed a hypocellular bone marrow with no blast cells. He received granulocyte colony-stimulating factor (G-CSF) while in the hospital with reconstitution of the WBC, but the platelet count remained decreased. At the time of discharge, his laboratory evaluation showed a WBC of 4000/mm 3 , hematocrit of 26%, and platelet count of 14 000/mm 3 . Following discharge from the hospital, he continued to require weekly red blood cell and platelet transfusions and remained pancytopenic. A bone marrow aspirate and biopsy were performed at 2 months following the reinduction chemotherapy, which re- vealed a mildly hypercellular bone marrow (60% cellularity) with trilineage hematopoiesis and no evidence of leukemia. Megakaryo- cytes were decreased in number and normal in morphology and no dysplastic erythroid cells were identified. A repeat bone marrow aspirate and biopsy 1 month later revealed the same finding with no evidence of residual leukemia. Fluorescence in situ hybridization (FISH) analysis did not reveal the RUNX1/RUNX1T1 (formerly known as AML1/ETO) rearrangement. He now presents to our institution for a second opinion regarding postremission treatment options. His medical history is notable only for hypertension and a previous surgical procedure to repair an ankle fracture. His medications include valsartan and metoprolol. He has no known drug allergies. He denies any smoking history or known toxin exposure. He is married and lives with his wife and 3 children, all of whom are in good health. There is no family history of malignancy. The patient appeared well. The physical examination was completely normal. Laboratory test results revealed a WBC of 3000/mm 3 with an absolute neutrophil count of 900/mm 3 , hemato- crit of 34.6%, and platelet count of 37 000/mm 3 . Specimens from all the previous bone marrow aspirates and biopsies were reviewed and a management decision was made after additional test results were obtained. Discussion This patient with AML and the t(8;21), one of the CBF AMLs, was in apparent first complete remission (CR) (although the persistent cytopenias were unexplained) and sought advice regarding the best postremission strategy. The patient was given induction elsewhere initially with a cytarabine dose of 200 mg/m 2 . A randomized trial has demonstrated that doses of cytarabine of 100 mg/m 2 and 200 mg/m 2 when combined with daunorubicin lead to equivalent CR rates. Any potential benefit for the higher dose remains to be proven in a clinical trial. The dose of daunorubicin of 90 mg/m 2 /d for 3 days was appropriate considering that a large randomized trial in younger patients showed an improved outcome compared with the standard approved dose of 45 mg/m 2 . 1 He required 2 cycles of induction to achieve CR, which is the case in approximately 30% of patients with AML and the t(8;21)(q22;q22), and necessitating 2 cycles does not confer a less favorable prognosis compared with patients who achieve CR with a single cycle. 2 It appears that no change in postremission therapy is required. Historically, patients with CBF AML have been reported to have a relatively favorable outcome when treated with conven- tional induction and intensive consolidation chemotherapy. 3 The standard postremission approach for a patient with a CBF AML is to administer 3-4 cycles of high-dose cytarabine or other intensive chemotherapy. Many, but not all, studies have suggested that leukemia cells from patients with CBF AML are particularly sensitive to high-dose cytarabine and that multiple cycles lead to a higher cure rate than 1. However, no definitive randomized trial testing this hypothesis has been conducted. Furthermore, other studies have demonstrated that the same relatively favorable outcome can be achieved with multiple cycles of intensive chemotherapy other than high-dose cytarabine. Submitted December 27, 2010; accepted January 9, 2011. Prepublished online as Blood First Edition paper, February 1, 2011; DOI 10.1182/blood- 2011-01-326819. © 2011 by The American Society of Hematology 2775 BLOOD, 10 MARCH 2011  VOLUME 117, NUMBER 10 For personal use only. on June 22, 2016. by guest www.bloodjournal.org From