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  • Lomustine In addition further study is required to evaluate

    2019-05-15

    In addition, further study is required to evaluate whether identified mutations influence post-translational Lomustine modifications because they are important mechanism of transcription factors for regulating normal and leukemic hematopoiesis.
    Authors\' contributions
    Conflict of interest
    Acknowledgments We would like to thank Ms. Manami Kira, Mirei Okamoto and Satomi Yamaji for secretarial and technical assistance. This study was supported by Grants-in-Aid from the Ministry of Health, Labor and Welfare for Cancer Research (Clinical Cancer Research ) and the National Cancer Center Research and Development Fund (23-A-23), the Scientific Research Program of the Ministry of Education, Culture, Sports, Science and Technology, and the Global COE Program “Integrated Functional Molecular Medicine for Neuronal and Neoplastic Disorders” Japan.
    Introduction Patients with acute myeloid leukemia (AML) are at increased risk for developing serious infections after receiving cytotoxic chemotherapy. Admission to hospital and administration of broad spectrum Lomustine is thus standard should patients develop fever while neutropenic (NF). However, discharge practices vary once such patients become afebrile, with many patients remaining hospitalized until rise in their absolute neutrophil count (ANC) to >500/μL (ANC recovery). There are several reasons to question this practice. First, today\'s antibiotics are probably more effective than those available when the practice was initiated. Second, Bodey et al. noted that at a given neutrophil count <1000 infections were less common in patients in remission than in those not. Third, keeping patients in hospital until ANC recovery increases their exposure to hospital-acquired infections and may decrease psychological well-being. Finally, this policy increases costs and/or decreases the availability of beds for patients more in need of urgent care. These considerations motivated us to retrospectively compare rates of re-admission, admission to ICU, and death (from the event prompting re-admission) according to discharge ANC in patients discharged from hospital after apparent successful treatment of NF. Here we report our results.
    Materials and methods After obtaining IRB approval we reviewed the medical records (accessed electronically) of 144 patients given chemotherapy for newly-diagnosed AML at the University of Washington/Seattle Cancer Care Alliance (UW/SCCA) between January 2008 and May 2010. Essentially all 144 received “3+7” or “more intense” regimens, particularly those containing ara-C at a daily dose ≥1g/m2. Forty-nine of the 144 were admitted because of NF (a single oral temperature ≥38.3°C or a temperature ≥38°C for ≥1h unrelated to transfusion and accompanied by an ANC of <500/μL, or >500/μL with a predicted decline to <500/μL, in accordance with 2010 Infectious Disease Society of America criteria). For each of the 49, this admission was the first for NF. Patients were included regardless of whether monocytes were receiving induction or post-remission therapy and regardless of whether or not they were in complete remission (CR). Thirty-five of the 49 (71%) were thought to be in CR or were shown to be in CR at the next marrow exam.
    Results Table 1 shows some characteristics of the 49 patients. Thirteen (27%) patients were re-admitted, all for NF. The rate of readmission increased as the discharge ANC became lower (p=0.03). However the ANC 500 cut-off point did not clearly distinguish patients who were and were not re-admitted (Table 1). Nor was there a relation between the ANC at discharge (actual value or <500 vs >500) and subsequent need for ICU admission. One patient died within 30 days of discharge. She was a 55 year old who was discharged afebrile with ANC of after a hospital stay of 21 days; the cause of this fever was not determined. She was re-admitted with fever the next day while her ANC remained 0. She was intermittently febrile and 14 days after re-admission blood cultures grew Stenotrophomonas maltophilia leading to her death, at which time her ANC remained 0. This history suggests that the infection that led to her death was acquired in the hospital.