Cefepime-induced encephalopathy in patients with haematological malignancies: clinical features and risk factors.

BACKGROUND: Cefepime is an antibiotic that is widely used in patients with haematological malignancies (HM). Although its use has been reported to be associated with encephalopathy, only case reports or small case series have been reported so far. PATIENTS AND METHODS: We conducted a retrospective cohort study of 243 patients with HM treated with cefepime at our hospital between August 2011 and May 2013. We also investigated the clinical features of patients with cefepime-induced encephalopathy (CIE). RESULTS: Among 243 HM patients treated with cefepime, 10 were diagnosed with CIE, indicating a cumulative incidence of approximately 4.1%. The median creatinine level on commencement of treatment was 2.13 mg/dl (range 0.60-19.85) and the median initial dose of cefepime was 4.0 g/day (range 1.0-6.0). The median time between commencement of treatment and symptoms was 4.0 days (range 2-5). The most common clinical manifestations were decreased level of consciousness and myoclonus. Symptoms resolved fully in all patients. Univariate analyses showed that impaired renal function (creatinine clearance (CLCr) < 30 ml/min, acute renal failure, and chronic dialysis) was significantly associated with the development of CIE (univariate p < 0.0001, p = 0.020, and p = 0.0025, respectively). Receiver operating characteristic (ROC) analysis demonstrated that the threshold levels of creatinine, CLCr, and estimated glomerular filtration rate for CIE were 1.22 mg/dl, 22.96 ml/min, and 43.9 ml/min/1.73 m(2), respectively. CONCLUSIONS: This study indicated that the development of CIE is associated with severely impaired renal function in patients with HM.

Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12.

A rare recurrent chromosomal translocation, t(14;19)(q32;q13), has been identified in a variety of B-cell malignancies, including chronic lymphocytic leukemia (CLL). We report a unique case of CLL in a patient carrying both trisomy 12 and t(14;19) (q32;q13.1), in whom t(11;14)(q13;q32) developed at relapse. The patient was a 77-yr-old woman, and her lymphoma cells at presentation showed CD5(+), CD10(-), CD19(+), CD20(+)(dim), CD23(+), CD38(+), and CD11c(+). At relapse, the patient's lymphoma cells showed positive staining for cyclin D1 in addition to CD5, CD20, and CD23. Lymphoma cells in specimens at both presentation and relapse were positive for lymphoid enhancer factor 1 (LEF1) and negative for sex-determining region Y-box 11 (SOX11). IGH-BCL1 FISH became positive at relapse. Split FISH assay using BCL1, BCL3, IGH, and CCND1 probes on lymph node specimens obtained at presentation and at autopsy confirmed that the translocation of BCL3 was solely detected in the lymph node at presentation and detected BCL3 and CCND1 translocations in the specimen at autopsy. These observations indicated that IGH-BCL3 and IGH-CCND1 had occurred in the same clone after treatment of the disease. In line with immunohistochemical and cytogenetic studies, additional PCR analysis of the FR3-JH region showed the same sequence derived from IGHV4-34 in specimens obtained at disease onset and relapse.

Normalization of free light chain kappa/lambda ratio is a robust prognostic indicator of favorable outcome in patients with multiple myeloma.

PURPOSE: To clarify the impact of serum free light chain (sFLC) ratio normalization in patients with multiple myeloma (MM) treated with novel agents. PATIENTS AND METHODS: Treatment response in 126 consecutive patients over 7 years was assessed by IMWG criteria and sFLC assay. RESULTS: Thirty-four patients (27%) showed complete response (CR), 37 (29%) very good partial response (VGPR), 39 (31%) partial response (PR), and 16 (13%) stable disease (SD) or less at a median follow-up of 28 months. Fifty-two patients (41%) with sFLC ratio normalization showed superior progression-free survival (PFS) and overall survival (OS) compared to those who did not (3-yr OS, 94% vs. 48%; P < 0.001). This favorable effect of sFLC ratio normalization occurred irrespective of high (>1000 mg/dL) or low (<100 mg/dL) baseline sFLC. Rates of normal sFLC ratio were as follows: CR, 69%; VGPR, 64%; PR, 16%; and SD or less, 0%. OS was significantly superior in patients with than without normal sFCL ratio in respective response groups. Although various factors (advanced age >70, high LDH, ISS stage 3) showed negative prognostic impacts on PFS and OS on univariate analysis, normal sFLC ratio and achievement of CR emerged as the strongest prognostic predictors for longer OS in MM patients on multivariate analysis. CONCLUSIONS: This study demonstrated the significance of obtaining normal sFLC ratio independent of other clinical variables. Analysis of sFLC ratio could identify the favorable group of patients as well as immunofixation test and support the inclusion of sFLC ratio as part of the response criteria for MM.