Hormographiella aspergillata, a filamentous basidiomycete, has rarely been involved in human infections. We describe 2 febrile neutropenic patients who developed a severe pulmonary infection due to H. aspergillata while receiving empirical caspofungin therapy for presumed fungal pneumonia. After introduction of liposomal amphotericin B, one patient, who had neutrophil recovery, presented a favorable outcome, while the other, who remained neutropenic throughout the course of infection, died. Resistant fungi, including basidiomycetes, may emerge during empirical treatment with caspofungin in febrile neutropenic patients. A rapid switch to any other potent antifungal should be rapidly considered in case of failure of caspofungin in this setting. CASE REPORTSCase description for patient 1. A 23-year-old female was diagnosed with biphenotypic acute leukemia. She received induction chemotherapy associating idarubicine, high-dose cytarabine, and corticosteroids. Because of her persistent fever while receiving large-spectrum antibiotics for febrile neutropenia, empirical caspofungin was added (70 mg on day 1, followed by 50 mg daily thereafter). Fever persisted, and she developed a dry cough and scapular pain on day 23. Serum galactomannan antigen (GMA) was repeatedly negative, and blood cultures were sterile. A chest X-ray showed an upper right lobe infiltrate, and a computed tomography (CT) scan demonstrated a nodular infiltrate surrounded by a halo sign. Caspofungin was replaced after 20 days by voriconazole (400 mg per day) for possible pulmonary aspergillosis. Despite hematological recovery and complete remission, a control CT scan on day 36 showed a progression of the lung infiltrate. A transthoracic percutaneous puncture of the lesion was performed under CT scan guidance and showed the presence of rare septated hyphae under direct microscopic examination (Fig. 1). After 13 days of voriconazole, antifungal therapy was then changed to liposomal amphotericin B starting at 5 mg/kg of body weight/day, and the patient's condition improved, with a marked reduction of the pulmonary infiltrate. Liposomal amphotericin B was then reduced to 5 mg/kg on alternate days because of severe hypokalemia. Consolidation chemotherapy was delayed for 2 weeks because of uncontrolled infection, during which time she received oral treatment with 6-mercaptopurine and etoposide. She then proceeded to the consolidation phase and received three courses of chemotherapy before undergoing myeloablative conditioning and syngeneic stem cell transplantation from her twin sister 7 months later. Hematological recovery occurred on day 15. During neutropenia, she was maintained on liposomal amphotericin at 5 mg/kg/day until day 45, when all antifungal treatment was discontinued (total duration of liposomal amphotericin B, 8 months). Three years after stem cell transplantation, she is alive and cured from her invasive fungal infection.Case description for patient 2. A 27-year-old male with adult-onset X-linked adrenoleukodystrophy characterized by adren...

Multiple Myeloma (MM) is an incurable malignant plasma cell disorder. We have evaluated the counts of Multiple Myeloma Cells (MMCs) and normal plasma cells (N-PCs), seven days after high-dose melphalan (HDM) and autologous stem transplantation (ASCT). Two third of patients had detectable minimal residual disease (MRD+) (71.7 MMCs/μL) after induction treatment with dexamethasone and proteasome inhibitor. MMC counts were reduced by 92% (P ≤ .05) but not eradicated 7 days after HDM+ASCT. Post-HDM+ASCT MMCs were viable and bathed in a burst of MMC growth factors, linked with post-HDM aplasia. In one third of patients (MRD− patients), MMCs were not detectable after induction treatment and remained undetectable after HDM+ASCT. Major difference between MRD− and MRD+ patients is that N-PC counts were increased 3 fold (P < .05) by HDM+ASCT in MRD− patients, but were unaffected in MRD+ patients. Possible explanation could be that clearance of MMCs in MRD− patients makes more niches available for N-PCs. Thus, MMCs are not fully eradicated shortly after HDM, are bathed in high concentrations of MMC growth factors in an almost desert BM, are viable in short-term culture, which suggests providing additional therapies shortly after HDM to kill resistant MMCs before full repair of lesions.

Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m 2 (6-hr intravenous [IV]) and 3 mg/m 2 IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m 2 (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m 2 with doses ranging from 12-18 mg/m 2 IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m 2 . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m 2 . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.

2694 Poster Board II-670 Introduction: This study was performed to determine the maximum-tolerated dose (MTD) and the recommended dose (RD) of idarubicin in combination with methotrexate (MTX), vindesine (VDS) and prednisolone (PRED) given to previously untreated patients (pts) (60–70 years-old) with primary central nervous system lymphoma (PCNSL). Patients and Methods: MTX and VDS were respectively given at the fixed dose of 3 g/m2 (6-hour intravenous [IV]) and 3 mg/m2 IV both on day 1. PRED was given at the fixed dose of 60 mg/m2 (IV or per os) on day 1 to 5. Idarubicin was administrated IV on day 1 with doses starting at 12 mg/m2 and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks, three times. G-CSF was used. Intrathecal chemotherapy (MTX 15 mg, cytarabine 40 mg ) was performed on day 1. Subsequent whole brain irradiation (30 Gy + 10 Gy on residual mass) was performed. Limiting toxicity was defined as grade 4 neutropenia for more than 7 days or thrombopenia grade 4 or extra haematological toxicity more than grade 2. Results: Between 2000 and 2005, 35 immunocompetent pts (19 men, 16 women) with a new diagnosis of PCNSL received 87 cycles at four different idarubicin dose levels. At dose level 1 (12 mg/m2) and level 2 (14 mg/m2), only one of six developed a limiting toxicity. About 3 cases, no limiting toxicity was observed at level 3 (16 mg/m2). Three of six developed a limiting toxicity at level 4 (18 mg/m2) which was considered as MTD. Fourteen patients were enrolled at level 3 to confirm the data. At level 3, main haematological toxicities were neutropenia grade 3 (9%) or grade 4 (40%) and main extra haematological toxicities were infectious disease (5 % grade 3 or 4) and renal failure (grade 2: 9%). Median survival time was 385 days (IC95% 136–679).Overall response rate after radiotherapy was 65.7 % (15 CR, 7 PR). Conclusion: Our study suggests that the RD of idarubicin administrated with MTX, VDS and PRED, should be 16 mg/m2 on day 1 every 21-day cycle. Disclosures: Delwail: Innate Pharma: Honoraria.

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