Tomotaka Ugai

Antibiotic prophylaxis in hematopoietic stem cell transplantation. A meta-analysis of randomized controlled trials.

OBJECTIVES We performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients. METHODS We collected reports from PubMed, the Cochrane Library, EMBASE, CINAHL, and Web of Science, along with references cited therein. We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. RESULTS Seventeen trials with 1453 autologous and allogeneic HSCT recipients were included. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotics in two trials. Systemic antibiotics other than fluoroquinolones were evaluated in five of these 12 trials. Four trials evaluated the effect of the addition of antibiotics for gram-positive bacteria to fluoroquinolones. One trial compared two different systemic antibiotic regimens: fluoroquinolones versus trimethoprim-sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95%CI 0.09-0.30), clinically or microbiologically documented infection (OR 0.38; 95%CI 0.22-0.63) and bacteremia (OR 0.31; 95%CI 0.16-0.59) without significantly affecting all-cause mortality or infection-related mortality. CONCLUSIONS Systemic antibiotic prophylaxis successfully reduced the incidence of infection. However, there was no significant impact on mortality. The clinical benefits of prophylaxis with fluoroquinolones were inconclusive because of the small number of clinical trials evaluated.

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

To clarify the impact of serum free light chain (sFLC) ratio normalization in patients with multiple myeloma (MM) treated with novel agents.

Risk factors for pre‐ and post‐engraftment bloodstream infections after allogeneic hematopoietic stem cell transplantation

Bloodstream infections (BSI) are frequently observed after allogeneic hematopoietic stem cell transplant (HSCT), and could cause morbidity and mortality.

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 patients 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.

High Incidence of Afebrile Bloodstream Infection Detected by Surveillance Blood Culture in Patients on Corticosteroid Therapy after Allogeneic Hematopoietic Stem Cell Transplantation.

Bloodstream infections (BSI) are still important complications after allogeneic hematopoietic stem cell transplantation (allo-SCT). Patients who are receiving corticosteroid therapy can develop BSI without fever. The utility of surveillance blood cultures in these situations is controversial. We retrospectively analyzed 74 patients who received a corticosteroid consisting of ≥.5 mg/kg prednisolone or equivalent after allo-SCT. In principle, we performed surveillance blood culture weekly for these patients. Sixteen patients (21.6%) developed definite BSI. In a multivariate analysis, a myeloablative conditioning regimen, high-risk disease status at allo-SCT, and the presence of a central venous catheter at the initiation of corticosteroid therapy were identified as independent significant risk factors for the development of definite BSI. At the first definite BSI episode, 7 patients (46.7%) were afebrile and diagnosed by surveillance blood culture. However, 6 of these 7 afebrile patients showed various signs that could be attributed to infection at the time of positive blood culture. In conclusion, patients receiving corticosteroid therapy after allo-SCT frequently develop afebrile BSI. Although surveillance blood culture might be beneficial in these situations, it also seems important to not miss the signs of BSI, even when patients are afebrile.

Reduced-dose (two-thirds) R-CHOP chemotherapy for elderly patients with non-Hodgkin lymphoma.

Abstract Elderly patients with non-Hodgkin lymphoma (NHL) have a poor prognosis. Owing to treatment-related toxicities, there is no standard chemotherapy for the elderly patients, especially those aged 70 years or older. In this study, we retrospectively evaluated the efficacy and toxicity of reduced-dose (two-thirds) R-CHOP chemotherapy as an initial chemotherapy for 45 patients aged 70 years or older with B-cell NHL. The WHO classification of NHL included diffuse large B-cell lymphoma (DLBCL) (31), mantle cell lymphoma (5), follicular lymphoma (4), extranodal marginal zone lymphoma (1), Burkitt lymphoma (1), and B-cell lymphoma whose further types were unclassified (3). The incidences of grade 4 neutropenia and febrile neutropenia (FN) were 51·1 and 15·6%, respectively. Efficacy was evaluated in patients with DLBCL. The overall and complete response (CR) rates were 96·7 and 90·0%, respectively. Two-year event-free survival (EFS) and overall survival (OS) were 84·4 and 89·2%, respectively. There was no treatment-related mortality. In conclusion, two-thirds R-CHOP chemotherapy is a promising treatment for elderly patients with B-cell NHL in terms of its efficacy and toxicity.

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

Abstract 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 m2, respectively. Conclusions: This study indicated that the development of CIE is associated with severely impaired renal function in patients with HM.

Significance of a positive Clostridium difficile toxin test after hematopoietic stem cell transplantation

Patients with hematological malignancies show a high prevalence of asymptomatic colonization with Clostridium difficile (CD colonization). Therefore, it is difficult to distinguish CD colonization with diarrhea induced by a conditioning regimen from true Clostridium difficile infection (CDI) in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively analyzed 308 consecutive patients who underwent a CD toxin A/B enzyme immunoassay test for diarrhea within 100 d after HSCT from November 2007 to May 2014. Thirty patients (9.7%) had positive CD toxin results, and 11 of these had positive results in subsequent tests after an initial negative result. Allogeneic HSCT, total body irradiation, stem cell source, acute leukemia, and the duration of neutropenia were significantly correlated with positive CD toxin results. In a logistic regression model, allogeneic HSCT was identified as a significant risk factor (odds ratio 18.6, p < 0.01). In an analysis limited to within 30 d after the conditioning regimen, the duration of neutropenia was the sole risk factor (odds ratio 10.4, p < 0.01). There were no distinctive clinical features for CDI, including the onset or duration of diarrhea. In conclusion, although CDI may be overdiagnosed in HSCT recipients, it is difficult to clinically distinguish between CDI and CD colonization.

A retrospective analysis of computed tomography findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation

OBJECTIVE The purpose of this study was to review the high-resolution computed tomography (CT) findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT), and to evaluate the relationship between CT findings and clinical outcomes. PATIENTS AND METHODS We collected the clinical data in 96 consecutive patients who underwent CT scan for pulmonary complications after allogeneic HSCT and analyzed the relationships among these clinical characteristics, CT findings and clinical responses. Radiologists who were blinded to clinical information evaluated the CT findings. RESULTS In multivariate analyses, the presence of chronic graft-versus-host disease (GVHD) and non-segmental multiple consolidations were significantly associated with a poor response to antimicrobial therapies, and the disease risk was significantly associated with a poor corticosteroid response. In addition, the existence of cavity formation and pleural effusion were significantly associated with a fatal prognosis. Twenty-five patients underwent bronchoscopic examination and 4 of them also underwent transbronchial lung biopsy (TBLB), but diagnostic information was not obtained in 15 patients. There was no significant association between specific CT findings and the diagnosis based on bronchoscopic examination. CONCLUSIONS No specific CT finding was identified as a predictor for either an antimicrobial response or for a corticosteroid response in this study. The presence of cavity formation and pleural effusion may predict a poor prognosis.

Prediction of infectious complications by the combination of plasma procalcitonin level and localized infection before allogeneic hematopoietic cell transplantation.

We previously reported that the baseline C-reactive protein level did not predict infectious events after hematopoietic cell transplantation (HCT). Procalcitonin (PCT) has recently emerged as a powerful biomarker for the early diagnosis of bacterial infection. We evaluated the ability of the baseline PCT level to predict early infectious events after HCT in 79 recipients who received HCT between 2008 and 2012. The high-PCT group (⩾0.07 ng/mL, n=27) frequently experienced documented infection (DI) (21.2% vs 44.4% at day 30, P=0.038) and bloodstream infection (BSI) (15.4% vs 37.0% at day 30, P=0.035). In a multivariate analysis, however, the baseline PCT level was not significantly associated with DI (HR 2.01, P=0.089) or BSI (HR 2.28, P=0.084). Localized infection, such as anal canal problems, before the start of conditioning was seen in 26 patients. When we stratified the patients according to the presence of elevated PCT and localized infection, the group with elevated PCT and localized infection (n=17) was significantly associated with increased DI (HR 3.40, P=0.0074) and BSI (HR 3.59 P=0.0078) after HCT. A larger prospective observation is warranted to confirm the impact of the baseline PCT level and clinical features on the outcome of HCT.