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Infectious disease following hematopoietic SCT (HSCT) is a major cause of TRM. The more valuable markers to distinguish infections disease from non-infectious complications are needed. Procalcitonin (PCT) and C-reactive protein (CRP) were measured periodically throughout the clinical course of consecutive 28 patients who underwent HSCT. The diagnoses of 103 febrile episodes were analyzed. PCT and CRP level on the first day of fever significantly increased in systemic bacterial or fungal infection ( P <0.001 and <0.001, respectively). PCT is more valuable than CRP for discrimination between systemic bacterial or fungal infection and intracellular infection ( P =0.022 and 0.447, respectively). The area under receiver-operator characteristics curve for detection of bacterial or fungal infection was 0.82 for PCT and 0.76 for CRP. When PCT levels did not increase over 0.25 ng/mL through the fifth day of fever, PCT yielded a specificity of 100.0%. In multivariate analysis, the maximum level of PCT during a whole course of HSCT>=2 ng/mL was independently associated with worse overall survival as post-transplant predictors (adjusted hazard ratio 6.42, P =0.035). PCT provide additional information for discrimination between bacterial or fungal infection and other causes and predicting the patient’s prognosis after HSCT.

Chemotherapy-induced nausea and vomiting (CINV) is a serious complication of treatments of hematological malignancies. Although aprepitant, an NK1 receptor antagonist, has been shown to control CINV in highly emetogenic therapies for solid tumors, the antiemetic effect of this agent in hematological chemotherapies is not well established. In this randomized controlled trial, we examined the additional effect of aprepitant in combination with conventional 5HT3 blocker-based prophylaxis for CINV in highly or moderately emetic chemotherapies for hematological malignancies ( n  = 41). The complete response rate, defined as no emetic episodes and no salvage treatments, was significantly higher in the aprepitant arm than the control arm (82 versus 47 %, p  = 0.026), with no increase in severe adverse effects. However, the difference of nausea, measured with visual analog scale, and of oral intake impairment was moderate, which suggests insufficiency of blocking NK receptor for these events. Furthermore, sub-group analysis revealed that merit of aprepitant addition depends on treatment regimens. Our results indicate the overall advantage of applying aprepitant in the control of CINV in hematological malignancies and the need for further refinement of anti-CINV strategies, including stratification according to regimen.

Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1 ), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which—depending on lifestyle risks—may affect cancer development. In physiologically normal epithelia, age-related expansion of clones that carry mutations in NOTCH1 and other driver genes is accelerated by risk factors for developing oesophageal squamous cell carcinoma, such as alcohol consumption or smoking.

Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11,234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A , TET2 , JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH. Analysis of single-nucleotide variants and copy number alterations gives a more complete picture of clonal hematopoiesis and its impact on hematological malignancy and cardiovascular disease.

This retrospective study examined the differences in the prognostic impact of the haematopoietic cell transplantation-specific comorbidity index (HCT-CI) on transplant outcomes by disease status and time from transplant in allogeneic haematopoietic stem cell transplantation (HSCT) recipients at a Japanese transplant centre. Of 187 patients, nonrelapse mortality (NRM) at 3 years was 9.6, 21.2 and 27.8% in the low-risk (score 0), intermediate-risk (score 1–2) and high-risk (score ⩾3) HCT-CI groups, respectively ( P =0.03). The corresponding overall survival (OS) at 3 years was 70.1, 60.5 and 38.9%, respectively ( P <0.01). In multivariate analyses, high-risk HCT-CI significantly predicted higher NRM (relative risk, (RR) 2.44 (95% confidence interval, (CI) 1.02–5.85); P =0.04) and worse OS (RR 2.02 (95% CI 1.15–3.54); P =0.01). In the subgroup analysis according to disease status, the HCT-CI was associated with OS ( P <0.01) and NRM ( P =0.07) in patients with low-risk diseases, but not in those with high-risk diseases. Within patients who survived without relapse >1 year after HSCT, the HCT-CI did not predict OS ( P =0.59) or NRM ( P =0.31). These findings can be useful to determine the role of pretransplant comorbidity in allogeneic HSCT.

Late-onset noninfectious pulmonary complications (LONIPCs) are life threatening for allogeneic hematopoietic SCT (allo-HSCT) recipients. However, the impact of LONIPCs on survival has not been properly evaluated and little is known about treatment efficacy. We retrospectively investigated 290 allo-HSCT recipients in our institute and reviewed the clinical aspects of 44 patients who had been diagnosed with LONIPCs. LONIPCs were significantly associated with higher rates of chronic GVHD ( P <0001) and nonrelapse mortality ( P =0.013), and lower rates of relapse ( P =0.009). As a result of these effects, OS was significantly worse in those with LONIPCs ( P =0.003). This result differs from a previous report. We then assessed short-term treatment response and final outcome. These results were defined by radiological findings, subjective symptoms, oxygen requirement and survival. Use of inhaled and systemic steroids did not affect either short-term response or final outcomes. However, administration of systemic corticosteroids earlier than at 21 days (median interval of time from onset of symptoms to systemic corticosteroids administration) was associated with a better outcome ( P =0.054 for short-term response, and 0.016 for final outcome). Our study indicates that LONIPCs reduce OS, and early intervention with systemic corticosteroids may be effective.

UR 150 Pneumonia

Although previous invasive fungal diseases (IFD) pose a significant risk of reactivation during successive chemotherapies in patients with acute leukemia, and secondary antifungal prophylaxis is regarded as mandatory, much remains unknown about the optimal strategy including the efficacy of voriconazole. During January 2006 and October 2008, a total of 15 patients with acute leukemia had pulmonary IFD (4 probable and 11 possible cases) before or during chemotherapy. After successful treatment of primary IFD with oral voriconazole, all of them received voriconazole during a total of 35 courses of successive chemotherapy. All but one patient successfully accomplished planned treatment without suspected IFD or significant toxicity despite profound neutropenia. We retrieved the previous reports of myelosuppressive therapies after IFD using various secondary prophylaxes, and showed that voriconazole is the most effective drug to suppress IFD relapses.