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A 54-year-old woman with acute myeloid leukemia (AML) achieved complete remission by induction chemotherapy, but developed zygomycosis after consolidation therapy. As zygomycosis could not be cured by liposomal amphotericin B and micafungin, left lower lobectomy was performed. As AML relapsed 7 months after onset, she received haploidentical stem cell transplantation under administration of liposomal amphotericin B. Despite experiencing severe acute graft-versus-host disease, she remains alive with no relapse of either zygomycosis or AML.

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.

Background: Indications for allogeneic hematopoietic stem cell transplantation (allo-HCT) with reduced-intensity conditioning (RIC) have expanded widely for elderly patients and those with comorbidities. However, the optimal RIC regimen remains uncertain. A combination of fludarabine phosphate (Flu) and melphalan (Mel) is widely used in RIC regimen with comparable results to that of fludarabine phosphate and busulfan. In our hospital, Flu/Mel and low-dose total body irradiation (Flu/Mel/TBI) is mainly used in RIC regimen. We analyzed safety and efficacy in allo-HCT patients with Flu/Mel/TBI. Methods: This study was a retrospective analysis of patients with hematopoietic malignancies who received their first allo-HCT with Flu/Mel/TBI from between January 2005 to December 2015. Patients were included for Flu/Mel/TBI treatment for elderly, those with a recent fungal infection or organ dysfunction. Flu/Mel/TBI consists of intravenous Flu (125-150 mg/m2), Mel (140 mg/m2), and TBI (2-4 Gy). GVHD prophylaxis consists of tacrolimus and short-term methotrexate with or without low-dose anti-thymocyte globulin (ATG). The primary end point was non-relapse mortality (NRM) on day 100. As the secondary end point, we verified the effects about Flu/Mel/TBI for patients with non-remission. Results: From January 2005 to December 2015, 168 patients received conditioning regimens with Flu/Mel/TBI. The median age was 59 years (16-71 years). Hematopoietic malignancies consisted of acute myeloid leukemia (AML) (n=74), myelodysplastic syndrome (MDS) (n=63), acute lymphoblastic leukemia (ALL) (n=12), malignant lymphoma (ML) (n=10), chronic myeloid leukemia (CML) (n=5), adult T-cell leukemia (ATL) (n=2), acute myeloid/NK cell leukemia (n=1), and chronic active Epstein-Barr virus infection (CAEBV) (n=1). Twenty-eight donors were HLA matched siblings, 6 were mismatched siblings, and 2 were haplo-identical donors. Of these, 55 had matched unrelated bone marrow donors, and 47 had 1-allele mismatched unrelated donors and 30 cord blood donors. With regard to disease status at allo-HCT, 44 patients (26.0%) were in remission and 124 patients (74.0%) were non-remission. Forty-nine patients were administered low-dose ATG. The median observation period of survivors was 2021 days (758-4660 days). Neutrophil engraftment was achieved in 89.3%. Median neutrophil recovery to over 500/µl was obtained on day 19 (11-87). Cumulative incidence of NRM at day 100 was 17.4%. Early death, defined as death before day 100, from allo-HCT occurred in 32 patients. Three patients had early relapse. Causes for NRM were infection in 15 patients (8 pneumonia, 7 sepsis), acute cardiac failure in 3 patients, cerebral hemorrhage in 2 patients, thrombotic microangiopathy in 2 patients, acute GVHD in 1 patient, hemophagocytic syndrome in 1 patient, and 5 other causes. NRM rates at day 100 by disease status at allo-HCT showed no significant differences (remission: 15.9% vs non-remission: 17.9%, p=0.15). Overall survival (OS) and disease-free survival (DFS) at 2 years were 50.6% and 43.5%, respectively. Survival rates with regard to disease status showed significant differences. Patients in remission had a 2-year OS of 65.9%, whereas patients in non-remission had a 2-year OS of 45.2% (p=0.031). Patients in remission had a 2-year DFS of 59.1%, whereas patients in non-remission had a 2-year DFS of 37.9% (p=0.016). Cumulative incidences of grade 2-4 and 3-4 acute GVHD were 30.7% and 17.1%, respectively. Cumulative incidence of relapse at 2 years was 29.8%. Conclusion: The current study proved that disease status at allo-HCT were mainly in non-remission. In such a situation, RIC using Flu/Mel/TBI was well tolerated with relatively low NRM, and was sufficient to allow engraftment for elderly or frail patients with hematopoietic malignancies. Disclosures No relevant conflicts of interest to declare.