Induction Chemotherapy with N(4)-behenoyl-1-beta-D-arabinofuranosylcytosine, Idarubicin and 6-Thioguanine in Childhood Acute Myelogenous Leukemia / 대한소아혈액종양학회지

PURPOSE: Retrospective study was performed to evaluate the survivals, remission rate and complications of induction chemotherapy using N(4)-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), idarubicin and 6-thioguanine (6-TG) in newly diagnosed childhood acute myelogenous leukemia. METHODS: From July 1994 to March 2000, 40 children (male 30, female 10) were enrolled in the study. From day 0 to 6 of induction, BH-AC 300 mg/m(2)/day was administered intravenously over 3 hours and from day 7 to 9, dosage was adjusted according to residual leukemic blasts in day 7 bone marrow aspirates. Idarubicin 10 mg/m(2)/day was administered intravenously over 15 minutes from day 0 to 2 and 6-TG 100 mg/m(2)/ day orally divided in two from day 0 to 6. Median age at diagnosis was 4.4 years (1 month~14.9 years) with a distribution according to the FAB classification of 1 M1, 10 M2, 13 M4, 5 M4E, 7 M5a, 3 M6 and 1 M7. RESULTS: Complete remission (CR) rate was 82.5% (33/40) with one cycle of induction chemotherapy and 90.0% (36/40) with additional cycle (BH-AC and idarubicin). One patient achieved partial remission with one cycle and was lost to follow-up, and 3 died of septic shock with disseminated intravascular coagulopathy during induction. Median time to CR from diagnosis was 28 days (25~68) and recovery from neutropenia (ANC> 1,000/muL) was achieved on median day 24 (21~44). All 40 patients had a fever during neutropenic period. Toxicities such as diarrhea, mucositis, nausea and vomiting were observed over half of the patients but tolerable and transient. Five-year overall, relapse- free and event-free survivals were 54.0%, 51.1% and 46.7%, respectively. CONCLUSION: These data show that this regimen is superior to others with high remission rate and well tolerated.

A Preliminary Report of Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia Conditioned by Triple-alkylating Regimen / 대한혈액학회지

BACKGROUND: We assessed the toxicity and feasibility of the three-alkylator combinations as conditioning regimens for allogeneic hemopoietic stem cell transplantation (HSCT) in 23 adult patients with acute leukemia. METHODS: Sixteen patients were transplanted for acute myeloid leukemia, six for acute lymphoblastic leukemia, and one for myelodysplastic syndrome. Group A included thirteen cases of relapsed refractory, 2 relapsed after first HSCT and group B eight patients in first complete remission or two in second complete remission. Eleven cases received G-CSF mobilized CD34+allogeneic peripheral blood stem cells (PBSCs) in addition to bone marrow (BM) and three in vivo expanded BM by G-CSF and eight unmanipulated BM and one from syngeneic BM after conditioned with busulfan, thiotepa and melphalan (n=14) or cyclophosphamide, thiotepa and melphalan (n=6) or TBI, melphalan and thiotepa (n=3). RESULTS: Twelve of thirteen patients in group A patients engrafted successfully and only one patient failed to achieve complete remission (CR). All patients in group B had successful engraftment. The median days reaching absolute neutrophil count (ANC) more than 500/microliter and platelet more than 30,000/microliter in group A and group B were 13.4 days (7-22), 17.9 days (9-40) and 16.3 days (10-21), 22.6 days (13-38), respectively. Acute graft vs host disease (GVHD) developed in both groups with the incidence of seven (78%) for group A and six (60%) for group B. The major regimen-related toxicity was mucositis with incidence of 95.7% (22/23). The disease free survival rate after HSCT with median follow-up of 161 days (31-283 days) and 101 days (22-163 days) in each group were 24% and 62.5%, respectively. CONCLUSION: Although the observation period is limited, this study shows that the combination of triple-alkylating regimens are tolerable as a preparative regimen for allogeneic HSCT for both high-risk and standard-risk leukemic patients. We need to confirm effects of these regimens in prospective randomized-controlled studies in the future. (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 34.1% (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% in order, respectively. Univariate analyses showed that age (P=0.0274) and augmentation with BHAC (p=0.0334) were significant factors for achieving CR.

Induction Chemotherapy with BH-AC, Idarubicin, and 6-Thioguanine in Childhood Acute Myelogenous Leukemia

PURPOSE: We have undertaken this study to evaluate the effects of induction chemotherapy involving BH-AC, idarubicin, and 6-thioguanine (6-TG). METHODS: BH-AC 300mg/m2/day was administered intravenously over three hours for seven consecutive days. Idarubicin 12mg/m2/day was administered intravenously for three days. 6-TG 100 mg/m2/day was administered orally for seven days. Intrathecal ara-C was administered on the first day of treatment. RESULTS: Complete remission (CR) was achieved in 18 cases (66.7%), partial remission (PR) was achieved in 2 cases (7.4%). In previously untreated patients, complete reimission rate was 92.9% (13/ 14), in relapsed patients, 40% (2/5) and in the refractory patients, 37.5% (3/8). The remission duration until December 1996 was 45 to 630 days (median 133). Duration of the neutropenia (ANC<500/microliter) was 0 to 38 days (median 24). Side effects were nausea, vomiting (7/27, 25.9%), liver dysfunction (1/27, 3.7%), skin eruption (1/27, 3.7%), and mucositis (1/27, 3.7%). In all cases, fever developed in the neutropenic state (culture proven sepsis in 5 cases). Death occurred in 5 cases who achieved CR due to sepsis after chemotherapy (4 cases), intracerebral hemorrhage after bone marrow relapse (1 case). CONCLUSION: BH-AC, idarubicin, and 6-TG induction chemotherapy could be a useful induction chemotherapy treatment that combines supportive care for infection and bleeding.