BACKGROUND: N4-behenoyl-1-β-D-arabinofuranosylcytosine (BHAC) was introduced as an ara-C analogue which possesses a strong anti-leukemic effect, mainly because of its resistance to cytidine deaminase. The purpose of this study is to evaluate the effects of BHAC as an induction regimen. We studied induction chemotherapy using BHAC plus idarubicin (IDA) for patients with previously untreated acute myelogenous leukemia (AML).
METHODS: Seventy-eight patients eligible for the induction study were enrolled. The remission induction therapy consisted of IDA 12㎎/㎡ intravenously over 30 minutes dally on days 1 to 3 in combination with BHAC 300㎎/㎡ over 4 hours daily on days 1 to 7. Augmentation chemotherapy included following three regimens with a BHAC (dosage was increased to 400㎎/㎡ IV for 4 hours for three days), IDA(12㎎/㎡/d IV for 2 days) plus BHAC (300㎎/㎡/d IV for 3 days) and amsacrine (AMSA, 100㎎/㎡/d IV for 2 days) plus BHAC (300㎎/㎡/d IV for 3 days) based upon the results of bone marrow study on seventh-day (D7) of induction chemotherapy.
RESULTS: Complete remission(CR) was achieved in 63 patients(80.8%), 36 by the first induction therapy (3×7) and 27 by the augmentation therapy for more three days with BHAC (3×10). Moreover, 5 patients were treated with further second induction regimen and achieved CR(6.4%). Six patients(7.7%) were primary refractory and 4 aplastic death. The median lays reached ANC>500/㎕ and platelet>20,000/㎕ were 15 days (range, 3 to 50) and 17 days (range, 6 to 57), respectively. The treatment-related mortality during induction chemotherapy were four cases(5.1％) with sepsis (n=1), disseminated intravascular coagulopathy (n=1), marrow aplasia(n=1), and cerebral hemorrhage (n=1). Other nonhematological toxicities were manageable and tolerable.
Among patients achieved CR, 23 cases of allogeneic bone marrow stem cell transplantation (allo-BMSCT) and 14 cases of autologous peripheral blood stem cell transplantation (aPBSCT) were underwent. With a median follow-up of 293 days (range, 35∼510), the relapse rate was 35.1% (14/41 cases) in chemotherapy-only group and 13.5% (5/37 cases) in transplant-group. The probability of disease-free survival (DFS) at 2 years of chemotherapy-only group, aPBSCT group, and allo-BMSCT group were 20.1%, 44.9%, and 90%, respectively. The relapse-probability at 2 years of three groups were 76.1%, 55.1%and 11.1% inorder, respectively. Univariate analyses showed that age (P=0.0274) and augmentation with BHAC(p=0.0334) were significant factors for achieving CR.
CONCLUSION: These data indicate that IDA+BHAC induction chemotherapy seems to be comparable to other combinations for induction chemotherapy in AML. More longer follow-up period is needed for assessing the impact of BHAC-containing regimen on the outcome of autologous and allogeneic hematopoietic stem cell transplantation.

Keywords: BHAC, Induction chemotherapy, AML