1052 Poster Board I-74 Background: Until recently, intensive chemotherapy for acute myeloid leukemia (AML) did not necessarily lead to high success rates, partly because of deaths from infections due to the associated long-term neutropenic phase. However, the advent of effective antifungal agents or the use of granulocyte colony-stimulating factor (G-CSF) or macrophage colony-stimulating factor (M-CSF) has definitely reduced deaths from chemotherapy and has improved the results of treatment with intensive chemotherapy also in elderly patients. Objectives: The complete remission rate after remission induction therapy and the event-free survival (EFS) after postremission therapy were investigated in 165 patients (99 men and 66 women) with untreated de novo AML (excluding subtype M3) who were consecutively registered in a single institution between March 2001 and March 2009. The patients' ages ranged from 16 to 94 years (median: 59 years). There were 3 patients with M0, 18 patients with M1, 25 patients with M2, 25 patients with t(8;21), 35 patients with M4, 12 patients with M4Eo, 35 patients with M5, 10 patients with M6, and 2 patients with M7. Methods: Remission induction therapy consisted of 10 days of behenoyl-ara-C (BHAC) at 350 mg/m2 (300 mg/m2 for patients 70 years or older) and 4 days of idarubicin (IDA) at 12 mg/m2 (10 mg/m2 for 70 years or older). Further, if bone marrow examination revealed 5% or more residual blast cells on day 15, etoposide was additionally administered at a dose of 100 mg/m2 for 4 days. The efficacy of the remission induction therapy was evaluated after 1 course of treatment. The patients who had achieved remission underwent 9 courses of postremission therapy, which lasted 11 months. The details are omitted, but therapy with high-dose (2 g/m2 [1 g/m2 for patients 60 years or older]) cytarabine (HDAC)×10 plus 7 mg/m2 of mitoxantrone (MIT) ×3 was performed during the 1st and 9th courses. No HDAC was performed on the elderly aged above 75 years old. The intensive therapy with Aclarubicin (ACR) of 20 mg/body for 14 days and the maintenance therapy with a combination of BHAC 350 mg/m2×4 with ACR or IDA were repeated alternately every 6 weeks. Chemotherapies other than remission induction therapy and HDAC were performed in an outpatient clinic, and if the patients with the WBC decreasing to 1000/mm3 were hospitalized in the biological clean room. M-CS was administered for 7 days after the day following the end of chemotherapy, and subsequently G-CSF was administered until the WBC becomes to be 1000/mm3. Results: Complete remission (CR) was achieved in 143 of the 165 patients overall (86.7%), 113 of the 123 patients 69 years or younger (92.7%), and 29 of the 42 patients 70 years or older (69.1%). During the remission induction therapy, death occurred in 6 of the 165 patients overall (3.6%), 2 of the 123 patients 69 years or younger (1.6%), and 4 of the 42 patients 70 years or older (9.5%). The EFS in patients with CR was 61.5% at 8 years in patients 69 years or younger, while it was 26.9% at 5 years in patients 70 years or older. There was only a case of death due to chemotherapy during postremission therapy. Seven patients underwent bone marrow transplantation during the first remission, and 6 of these patients have been enjoying EFS. Conclusion: Improvement in supportive care has enabled safe intensive chemotherapy. The patients with good or intermediate prognosis were clearly improved by the present preliminary treatment at a single institution, but the patients with poor prognosis still highly require bone marrow transplantation in the future. Disclosures: No relevant conflicts of interest to declare.

1544 Since myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are more prevalent in the elderly, intensive chemotherapy is difficult. However, recent progress in supportive therapy, especially with anti-fungal agents, and diagnostic procedures for invasive fungal infection (IFI) such as β-D glucan (β-D), galactomannan antigen (GM) and computed tomography (CT), have resulted in dramatically enhanced safety of post-chemotherapy control of elderly patients. To evaluate the efficacy and safety of our diagnosis and treatment strategy for IFI, we examined 112 consecutive episodes in 110 patients who received remission induction therapy from December 15, 2009 to June 18, 2011, including new or recurrent patients with MDS related AML (MDS-AML) and those with AML without a history of invasive aspergillosis (IA). Diagnosis was MDS-AML in 88 episodes (relapse 18) and AML in 24 (M1 5,M2 9,M4 9,M6 1).The median age was 70 (range: 21–88). Remission induction therapy consisted of behenoyl-ara-C for 10 days and idarubicin for 4 days (For further details, please refer to 51st ASH abstract #1052; Taiichi Kyo et al). Patients were always admitted to a clean room until neutrophil recovery, and were routinely administered macrophage-colony stimulating factor (CSF) and granulocyte-CSF. Amphotericin-b syrup and itraconazole capsules were given as antifungal prophylaxis. IFI diagnostic procedures consisted of CT, GM, β-D and surveillance culture (SC). At the time of admission a control CT was taken. CT was repeated within 24 hours when pyrexia of ≥38.0°C occurred. If fever showed no improvement, CT was repeated every 3 days (X-ray was also taken). If any change suggesting infection was noted, treatment against IA was considered. GM, β-D and SC were all conducted twice a week from the time of admission until discharge. ≥0.5 GM was regarded as positive and the treatment against IA was started even if there was only one positive result. At present there is no worldwide consensus concerning β-D, thus we considered a value exceeding the cut-off value of the reagent as positive. Treatment was started when there were both a positive result and increasing fever; and treatment against IA or candidiasis depended on imaging findings. Even if β-D was negative, candida detected by SC or diarrhea combined with increasing fever was also an indication for treatment against candidiasis. IA was treated with voriconazole (VRCZ) and candidiasis with micafungin (MCFG). VRCZ and MCFC were administered at 200–300 mg/twice/day and 100–300 mg/day, respectively. When no sufficient effect was observed with VRCZ alone, MCFG was added. Complete remission (CR) and partial remission (PR) were achieved in 81/112 (72%) and 9/112 (8%) episodes, while in 19/112 (17%) no response was obtained and 3/112 (2.7%) episodes resulted in death during chemotherapy. CR rate was comparable among de novo MDS-AML (49/70, 70%), MDS-AML relapse (9/18, 50%) and AML (23/24, 96%). The cause of death associated with chemotherapy was bacteremia 1, bacteremia or IA 1, and cerebral hemorrhage 1. GM was positive in 48 (43%) episodes. The reason for this large number was probably the advanced age of the patients and the long term neutropenia [absolute neutrophil count <500 (median) 27 days]. In spite of higher IA morbidity, mortality rates seemed very low. Furthermore, although GM >2.5 indicates an unfavorable prognosis and >5.0 no hope of survival, none of our patients with GM >2.5 (10 patients) died of IA (2 died of other causes) and all patients with GM >5.0 (4 patients) survived. Candidemia was found in 2 patients (krusei 1, guilliermondii 1) and were treated succesfully. β-D was positive in 46 /112 (41%) episodes and 28/112 (25%) were also positive for GM. As for GM and β-D, GM positivity preceded that of β-D in 9/28 (32%); regarding GM and CT, GM positivity preceded the observation of CT findings in 13/30 (43%). At the beginning of this study, no control CT was obtained. But in the course of the study we found some patients who presented CT findings indicating IA, such as nodular lesions, but with no infection. Thus, we realized the need for a control CT to detect IA more accurately. Each diagnostic procedure has excellent characteristics but it is not sufficient by itself. The results of this single-center clinical study indicate that an improvement of antifungal therapy combined with a battery of diagnostic procedures may allow safe, intensive chemotherapy for many patients with MDS or AML. Disclosures: No relevant conflicts of interest to declare.

1503 (Objective) The treatment outcome of patients with Ph+ ALL has significantly improved since the advent of TKIs such as imatinib and dasatinib. However, the long-term survival of these patients is not necessarily high when bone marrow transplantation (BMT) is not performed. The present study was aimed at developing an effective combination of a TKI and chemotherapy for long-term survival of patients with Ph+ ALL but ineligible for BMT. (Subjects and Methods) Forty-three consecutive patients (18 men, 25 women) with previously untreated Ph+ ALL who visited our hospital between June 2001 and February 2011 were treated. The age range was 13 to 84 years (median: 57), and 21 were 60 years or older. Measurement of BCR-ABL fusion transcript levels was performed immediately in these patients, and imatinib (IM) was started at 600 mg/body/day (given daily as a rule) as soon as the patient tested positive. A remission induction regimen (chemotherapy) used commonly in acute myeloblastic leukemia (AML) patients at our hospital was combined with TKIs in the first 14 patients. Another remission induction regimen often used in ALL patients at our hospital was then combined with TKIs in the subsequent 29 patients. The AML remission induction regimen used idarubicin (IDR) at 12 mg/m2 for 4 days, behenoyl-ara-C (BH-AC) at 350 mg/m2 for 10 days, and prednisolone (PSL) at 40 mg/body (P.O.) for 10 days. PSL was initially given at 100 mg/body (P.O.) and then gradually reduced in the ALL remission induction regimen. Vincristine (VCR) at 1.3 mg/m2 (Days 1, 8, 15, and 22), daunorubicin at 60 mg/m2 (Days 1, 2, and 3), cyclophosphamide at 1200 mg/m2 (Day 2), and L-asparaginase at 3000 μ/m2 (Days 11, 13, 16, 18, and 20) were administered. The remission induction therapies were given in a sterile room. Macrophage colony-stimulating factor was given for 7 days from Day 11 and granulocyte colony-simulating factor from Day 19. A post-remission therapy commonly administered to AML patients at our hospital was given after remission for 1 year (ASH, 2009, abstract, no. 1052). High-dose cytarabine (at 2 g/m2 BID for 5 days but at 1 g/m2 BID in patients aged 60 years or older) (HD-AC) and mitoxantrone (MIT) at 7 mg/m2 × 3 were initially administered after remission. Maintenance/consolidation therapy was given by alternating BH-AC at 350 mg/m2 × 4 + aclarubicin at 20 mg/body × 6 and BH-AC at 350 mg/m2 × 4 + IDR at 10 mg/m2 × 1 + VCR at 1.3 mg/m2 (each for 35 days). IM was given daily at 600 mg/day simultaneously with the post-remission therapy. Dasatinib was used in the post-remission therapy of 8 patients at 140 mg/day. All of the TKIs were given to patients for 3 years after completion of chemotherapy. (Results) Complete remission (CR) was achieved in 41/43 (95%). CR was achieved in 13 out of 14 (93%) patients treated with the AML regimen and 28 out of 29 (97%) treated with the ALL regimen. DIC occurred in 31/41 (76%) during remission induction therapy. The follow-ups of patients achieving CR lasted for 5 to 128 months (median: 24 months). Ten patients (aged 25 to 54 years [median: 37]) underwent BMT at first CR. Thirty-one patients (aged 13 to 84 years [median: 63]) were assigned to the chemotherapy group. The 10-year overall survival (OS) calculated by the Kaplan-Meier method was 57% for 41 patients who achieved CR, 66% for 20 patients younger than 60 years, and 49% for 21 patients aged 60 years or older. The OS was 80% for 10 patients who underwent BMT at first CR and 47% for 31 patients in the chemotherapy group. The 50% OS of the chemotherapy group was 36 months. The 10-year event-free survival (EFS) was 50% for patients who achieved CR, 80% for patients who underwent BMT at first CR, and 43% for the chemotherapy group. The 50% EFS of the chemotherapy group was 33 months. Fifteen patients have relapsed, and a new chromosomal aberration was observed at relapse in 11/13 (85%). (Discussion) The results of the present report indicate that BMT is the first choice for post-remission therapy of Ph+ ALL. Fifty percent of patients aged 60 years or older, who account for about half of the patients with Ph+ ALL, have achieved long-term survival with the prolonged TKI + chemotherapy used in the present report. Relapse was also rare among patients who received the combination and maintained CR for 3 years or longer. A combination of an appropriate TKI and a chemotherapy regimen as well as careful monitoring for complications is likely to further extend the survival of patients with Ph+ ALL. Disclosures: No relevant conflicts of interest to declare.