Clinical characteristics and treatment outcomes of pulmonary invasive fungal infection among adult patients with hematological malignancy in a medical centre in Taiwan, 2008-2013.

BACKGROUND/PURPOSE: This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy. METHODS: All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus. RESULTS: During the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack of response to anti-fungal treatment (P < 0.001), and admission to the intensive care unit (ICU) (P < 0.001) were predictors of poor prognosis. However, only admission to the ICU was an independent predictor of poor prognosis for 12-week mortality (P = 0.022) based on multivariate analysis. CONCLUSION: Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.

Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS. METHODS: shRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance. RESULTS: Downregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P <  0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group. CONCLUSIONS: This study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group.

Hyperleukocytosis is associated with distinct genetic alterations and is an independent poor-risk factor in de novo acute myeloid leukemia patients.

OBJECTIVES: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited. METHODS: A total of 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications. RESULTS: Hyperleukocytosis, defined as initial white blood cell counts above 50 000/µL, occurred in 28.9% of AML patients. HL patients had higher incidences of FLT3-ITD, NPM1, DNMT3A, CEBPA, and TET2 mutations. Multivariate analysis demonstrated that HL was an independent poor prognostic factor for overall survival and disease-free survival in total patients, those with intermediate-risk cytogenetics and normal karyotype irrespective of genetic alterations. Intriguingly, HL predicted poor survival in CEBPA double mutated, NPM1 + /FLT3-ITD- and NPM1-/FLT3-ITD- patients. Further, HL patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR) had a significantly longer overall survival and disease-free survival than those without allo-HSCT. CONCLUSIONS: Hyperleukocytosis is an independent poor prognostic factor irrespective of cytogenetics and mutation status. Allo-HSCT in first CR seems to ameliorate the poor prognostic impact of HL.

Clinical and microbiological characteristics of bloodstream infections among patients with haematological malignancies with and without neutropenia at a medical centre in northern Taiwan, 2008-2013.

This study aimed to investigate the epidemiology and microbiology of bloodstream infections (BSIs) in patients with haematological malignancies. Clinical characteristics and microbiology of 2083 patients with haematological malignancy who were treated for BSI from 2008 to 2013 at a medical centre in Taiwan were retrospectively reviewed. Lymphoma (38.1%) was the most common, followed by acute myeloid leukaemia (30.9%). Of the 2090 non-duplicate BSI isolates, 1310 (62.7%) were recovered from patients with neutropenia. Of the Gram-negatives (53.7%), Escherichia coli was predominant (13.8%), followed by Klebsiella pneumoniae (9.5%), Acinetobacter calcoaceticus-baumannii (ACB) complex (5.7%) and Pseudomonas aeruginosa (4.0%). Of the Gram-positives (40.2%), coagulase-negative staphylococci were the most common (20.5%), followed by Enterococcus faecium (5.6%). Candida tropicalis (2.0%) was the most commonly encountered yeast (5.0%). Multidrug resistance (MDR) was identified in 21.8% of ACB complex isolates. Among the 57 Staphylococcus aureus isolates, 24 (42.1%) were resistant to oxacillin (MRSA), and among the 118 E. faecium isolates, 55 (46.6%) were resistant to vancomycin (VRE). The overall 14-day mortality rate was 12.9% (n = 269). There was no significant difference in 14-day mortality among patients with (13.4%) and without (11.9%) neutropenia (P = 0.315). Multivariate analysis revealed that age ≥60 years, prior allogeneic transplantation, BSI due to VRE (E. faecium) and shock were independent predictors of 14-day mortality. Gram-negative organisms continued to be the most common cause of BSI in patients with haematological malignancies during the period 2008-2013. There was a significant increase in the prevalence of VRE (E. faecium) and MDR-ACB complex isolates.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS).

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (P<0.001) as in NH-MDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients (P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.

Soluble PD-L1: A biomarker to predict progression of autologous transplantation in patients with multiple myeloma.

Autologous hematopoietic stem cell transplantation (AuHSCT) is standard in treating eligible multiple myeloma (MM) patients. However, the outcome after treatment is highly variable. We used ELISA to analyze the levels of soluble PD-L1 (suPD-L1) in bone marrow (BM) plasma from 61 patients with MM at 100 days after AuHSCT. Patients were classified into high (H) and normal-to-low (NL) groups depending on their suPD-L1 levels. Among patients who had a very good partial response (VGPR) or better after AuHSCT, those in the H-group had a shorter response period (RpSCT) as well as shorter overall survival (OS) than those in the NL-group. Multivariate analyses confirmed that a high suPD-L1 level and high-risk cytogenetic abnormalities are independent factors for RpSCT. Our data suggest that suPD-L1 in the BM plasma of MM patients who have VGPR or better after AuHSCT could be used as a biomarker to predict outcome.

Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study.

OBJECTIVE: Existing data regarding the risk of hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins are limited by the small sample size. This population-based study aimed to examine the association between exposure to hypoprothrombinemia-inducing cephalosporins and hemorrhagic events using National Health Insurance Research Database in Taiwan. DESIGN: A nationwide nested case-control study. SETTING: National Health Insurance Research database. PARTICIPANTS: We conducted a nested case-control study within a cohort of 6191 patients who received hypoprothrombinemia-inducing cephalosporins and other antibiotics for more than 48 hours. Multivariable conditional logistic regressions were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins (overall, cumulative dose measured as defined daily dose (DDD), and individual cephalosporins). RESULTS: Within the cohort, we identified 704 patients with hemorrhagic events and 2816 matched controls. Use of hypoprothrombinemia-inducing cephalosporins was associated with increased risk of hemorrhagic events (aOR, 1.71; 95% CI, 1.42-2.06), which increased with higher cumulative doses (<3 DDDs, aOR 1.62; 3-5 DDDs, aOR 1.78; and >5 DDDs, aOR 1.89). The aOR for individual cephalosporin was 2.88 (95% CI, 2.08-4.00), 1.35 (1.09-1.67) and 4.57 (2.63-7.95) for cefmetazole, flomoxef, and cefoperazone, respectively. Other risk factors included use of anticoagulants (aOR 2.08 [95% CI, 1.64-2.63]), liver failure (aOR 1.69 [1.30-2.18]), poor nutritional status (aOR 1.41 [1.15-1.73]), and history of hemorrhagic events (aOR 2.57 [1.94-3.41]) 6 months prior to the index date. CONCLUSIONS: Use of hypoprothrombinemia-inducing cephalosporins increases risk of hemorrhagic events. Close watch for hemorrhagic events is recommended when prescribing these cephalosporins, especially in patients who are at higher risk.

Clinical outcomes of primary intraocular lymphoma patients treated with front-line systemic high-dose methotrexate and intravitreal methotrexate injection.

A standard treatment for patients with primary intraocular lymphoma (PIOL) remains unclear. This study retrospectively analyzed the clinical features and outcomes of 19 patients with PIOL who were treated with a first-line therapy comprising combined intravenous high-dose methotrexate and intravitreal methotrexate between January 2003 and December 2013. Thirteen (68.4 %) patients were female, and the median age at diagnosis was 57 (39-77 years). Diagnoses were based on the identification of abnormal lymphoid cells in vitreous fluid. Ten (52.6 %) patients had bilateral eye involvement, and six had concurrent central nervous system (CNS) involvement. All 19 patients achieved complete remission (CR) as confirmed by cytological examination of vitreous and cerebrospinal fluid and brain imaging if CNS was involved. Patients with concurrent brain involvement required a longer time to achieve CR. However, the duration of complete remission did not differ between patients with and without CNS involvement. The 5-year overall survival rate was 55.8 % for the total cohort and was higher (68.8 %) in patients with isolated PIOL than in those with concurrent CNS involvement. In all patients, methotrexate treatment was well tolerated, with manageable side effects. We conclude that combined intravitreal methotrexate and systemic high-dose methotrexate treatment is effective in patients with PIOL.

Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia.

Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.8% of total cohort and 13.2% of those with intermediate-risk cytogenetics. SF mutations were closely associated with RUNX1, ASXL1, IDH2 and TET2 mutations. SF-mutated AML patients had a significantly lower complete remission rate and shorter disease-free survival (DFS) and overall survival (OS) than those without the mutation. Multivariate analysis demonstrated that SFmutation was an independent poor prognostic factor for DFS and OS. A scoring system incorporating SF mutation and ten other prognostic factors was proved very useful to risk-stratify AML patients. Sequential study of paired samples showed that SF mutations were stable during AML evolution. In conclusion, SF mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. These mutations may be potential targets for novel treatment and biomarkers for disease monitoring in AML.

Higher Decorin Levels in Bone Marrow Plasma Are Associated with Superior Treatment Response to Novel Agent-Based Induction in Patients with Newly Diagnosed Myeloma - A Retrospective Study.

The growth of myeloma cells depends on bone marrow (BM) stroma consisting of stromal cells, secreted cytokines and the extracellular matrix (ECM). Decorin, a small leucine-rich proteoglycan in the ECM, is a signaling ligand and native anti-tumor agent. However, the role of decorin in patients with myeloma is not clear. We evaluated the correlation between the decorin levels measured by enzyme-linked immunosorbent assay in BM plasma from 121 patients with newly diagnosed myeloma based on their clinical features and treatment response. The median decorin levels in the patients and the normal control group were 12.31 ng/mL [standard deviation (SD), 7.50 ng/mL; range, 2.45 to 44.46 ng/mL] and 10.31 ng/mL (SD, 2.42 ng/mL; range, 4.85-15.14 ng/mL), respectively (P < 0.001). Using 15.15 ng/mL as a cut-off, 46 patients (38%) exhibited higher decorin levels (H-DCN), whereas the other patients exhibited normal to lower decorin levels (NL-DCN). Except for the median age, which was significantly younger in the H-DCN than in the NL-DCN group (60.6 ± 14.0 vs. 65.8 ± 12.2 years, respectively; P = 0.034), there were no differences between the two groups. However, in 79 patients who had received novel agent-based induction, the overall response rate was significantly better in the H-DCN than in the NL-DCN (97 vs. 63%, respectively; P < 0.001), as was the depth of responses (P = 0.008), which were not observed in those who had received chemotherapeutic agents alone. Progression-free survival (PFS) was significantly longer in H-DCN than NL-DCN (not reached vs. 19.5 mo, respectively; P = 0.0003). Multivariate analyses indicated that H-DCN, as a significantly independent factor, was associated with better treatment response (odds ratio, 20.014; 95% CI, 2.187-183.150; P = 0.008) and longer PFS (hazard ratio, 0.135; 95% CI, 0.051-0.361; P < 0.001). These findings disclose the potential role of decorin in myeloma and provide a basis for further study on possible synergistic anti-myeloma effects between decorin and the novel agents that target BM stroma.

High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan.

Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100-2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided.

Risk factors and clinical outcomes of acute myeloid leukaemia with central nervous system involvement in adults.

BACKGROUND: Acute myeloid leukaemia (AML) with central nervous system (CNS) involvement in adults is uncommon, and studies of this subject are scant. METHODS: We conducted a retrospective study to investigate the clinical aspects, cytogenetic abnormalities, molecular gene mutations and outcomes of adult AML patients with CNS involvement. Three hundred and ninety-five patients with newly diagnosed AML were reviewed. RESULTS: Twenty (5.1%) patients had CNS involvement, including 7 (1.8%) with initial CNS disease and 4 (1%) who suffered an isolated CNS relapse. The patients with CNS involvement were younger, had higher leukocyte, platelet, and peripheral blast cell counts, FAB M4 morphology, and chromosome translocations involving 11q23 (11q23 abnormalities) more frequently than did the patients without CNS involvement. No differences in sex, haemoglobin levels, serum LDH levels, immunophenotype of leukaemia cells, or molecular gene mutations were observed between the two groups. Multivariate analyses showed that age ≤ 45 years (OR, 5.933; 95% CI, 1.82 to 19.343), leukocyte counts ≥ 50,000/µl (OR, 3.136; 95% CI, 1.083 to 9.078), and the presence of 11q23 abnormalities (OR, 5.548; 95% CI, 1.208 to 25.489) were significant predictors of CNS involvement. Patients with initial CNS disease had 5-year overall survival and relapse-free survival rates that were similar to those without initial CNS disease. However, three of four patients who suffered an isolated CNS relapse died, and their prognosis was as poor as that of patients who suffered a bone marrow relapse. CONCLUSION: CNS involvement in adult patients with AML is rare. Three significant risk factors for CNS involvement including age ≤ 45 years, leukocyte counts ≥ 50,000/µl and the presence of 11q23 abnormalities were identified in this study. Future investigations to determine whether adult AML patients having these specific risk factors would benefit from CNS prophylactic therapy are necessary.

High Risk of Hepatitis B Reactivation among Patients with Acute Myeloid Leukemia.

BACKGROUND: Hepatitis B virus (HBV) infections are common and associated with significant morbidity and mortality in cancer patients. However, the incidence and risk factors of HBV reactivation in patients with acute myeloid leukemia (AML) are rarely investigated. METHODS: AML patients followed-up at the National Taiwan University Hospital between 2006 and 2012 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. RESULTS: Four hundred and ninety patients comprising 265 men and 225 women were studied. The median age was 52 years (range, 18 - 94). Chronic HBV carriage was documented at the time of leukemia diagnosis in 57 (11.6%) patients. Forty-six (80.7%) of the 57 HBV carriers received prophylaxis with anti-HBV agents. Sixteen HBV carriers (28.1%) developed hepatitis B reactivation during or after chemotherapy, including 7 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among AML patients with HBV carriage was 9.5 per 100 person-years. Prophylaxis with anti-HBV agents significantly decreased the risk of hepatitis B reactivation among HBV carriers (13% vs. 61%, p<0.001). Four (2.8%) of 142 patients with initial positive anti-HBsAb and anti-HBcAb experienced hepatitis B reactivation and lost their protective anti-HBsAb. Multivariate analysis revealed that diabetes mellitus (p=0.008, odds ratio (OR) = 2.841, 95% confident interval (CI): 0.985-8.193) and carriage of HBsAg (p<0.001, OR=36.878, 95% CI: 11.770-115.547) were independent risk factors for hepatitis B reactivation in AML patients. CONCLUSIONS: Hepatitis B reactivation is not uncommon in the HBsAg positive AML patients. Prophylaxis with anti-HBV agent significantly decreased the risk of hepatitis B reactivation.

A study of 65 patients with acquired hemophilia A in Taiwan.

BACKGROUND/PURPOSE: Acquired hemophilia A (AHA) is a rare disorder that has not been comprehensively reported in the Chinese population. Treatment-related fatal sepsis (TRS), other than hemorrhage, is the leading cause of death in patients with AHA. However, researchers have not systematically evaluated salient parameters, to determine their association with the risk of TRS in this rare disorder. This study reports the salient features of AHA in Chinese patients and presents possible factors associated with TRS. METHODS: Sixty-five Chinese patients with AHA, including 42 men and 23 women, were studied retrospectively. RESULTS: The median age was 64 years (range = 18-94 years). The features, laboratory findings, and outcomes of various therapies designed to arrest acute bleeding and eliminate autoantibodies against the factor VIII coagulant protein (VIIIi) were comparable to those previously reported. The complete response (CR) rate was 60%, and the median time to CR was 16 weeks. Ten patients (15%) died of bleeding related to FVIIIi by the end of the median follow-up period of 115 months. The estimated 1- and 5-year hemorrhage-related mortality rates were 15% and 22%, respectively. The absence of CR to therapy was the only independent factor associated with shorter survival. The rate of TRS was 20%, and the use of a rituximab-based (Rb) regimen (odds ratio = 8.0, 95% CI, 1.1-68.2) and platelet < 1.5 × 10(11)/L at diagnosis (odds ratio = 38.5, 95% CI, 1.3-1107.6) were the two significantly independent factors associated with TRS. CONCLUSION: The salient features of AHA and treatment outcomes of the patients in this study are similar to those of other patients. Two independent factors (the use of a Rb regimen and platelet < 1.5 × 10(11)/L) were significantly associated with TRS.

Clinical and prognostic implications of Roundabout 4 (robo4) in adult patients with acute myeloid leukemia.

BACKGROUND: Robo4 is involved in hematopoietic stem/progenitor cell homeostasis and essential for tumor angiogenesis. Expression of Robo4 was recently found in solid tumors and leukemia stem cells. However, the clinical implications of Robo4 expression in patients with acute myeloid leukemia (AML) remain unclear. METHODS: We investigated the clinical and prognostic relevance of mRNA expression of Robo4 in bone marrow (BM) mononuclear cells from 218 adult patients with de novo AML. We also performed immunohistochemical staining to assess the Robo4 protein expression in the BM biopsy specimens from 30 selected AML patients in the cohort. RESULTS: Higher Robo4 expression was closely associated with lower white blood cell counts, expression of HLA-DR, CD13, CD34 and CD56 on leukemia cells, t(8;21) and ASXL1 mutation, but negatively correlated with t(15;17) and CEBPA mutation. Compared to patients with lower Robo4 expression, those with higher expression had significantly shorter disease-free survival (DFS) and overall survival (OS). This result was confirmed in an independent validation cohort. Furthermore, multivariate analyses showed that higher Robo4 expression was an independent poor prognostic factor for DFS and OS in total cohort and patients with intermediate-risk cytogenetics, irrespective of age, WBC count, karyotype, and mutation status of NPM1/FLT3-ITD, and CEBPA. CONCLUSIONS: BM Robo4 expression can serve as a new biomarker to predict clinical outcomes in AML patients and Robo4 may serve as a potential therapeutic target in patients with higher Robo4 expression.

Clinical characteristics and treatment outcomes of patients with candidaemia due to Candida parapsilosis sensu lato species at a medical centre in Taiwan, 2000-12.

OBJECTIVES: To investigate the clinical characteristics and treatment outcomes of adult patients with Candida parapsilosis sensu lato candidaemia. METHODS: We evaluated data in the mycology database of the National Taiwan University Hospital and on patients diagnosed with candidaemia due to C. parapsilosis sensu lato species from 2000 to 2012. Isolates were identified to the species level by conventional identification methods, MALDI-TOF and gene sequencing analysis. RESULTS: A total of 323 adult patients with candidaemia caused by C. parapsilosis sensu lato species were evaluated, including 256 (79.3%) patients with C. parapsilosis sensu stricto, 34 (10.5%) with Candida orthopsilosis and 33 (10.2%) with Candida metapsilosis. There were 222 men and 101 women and the median age was 60 years (range 18-103 years). Among them, 178 (55%) had an underlying diagnosis of cancer. The overall 30 day mortality rate was 25% (n = 80). Multivariate analysis revealed that shock (P < 0.001), antifungal therapy (P = 0.002), central catheter removal (P = 0.02) and abdominal surgery (P = 0.043) were independent prognostic factors for patients with candidaemia due to C. parapsilosis sensu lato species. There were no significant differences in 30 day mortality rate among patients with candidaemia caused by the three different species (P = 0.770). All isolates of C. metapsilosis, C. orthopsilosis and C. parapsilosis sensu stricto were susceptible to voriconazole. WT isolates were susceptible to itraconazole, posaconazole and amphotericin B. CONCLUSIONS: There were no significant differences in 30 day mortality among patients with candidaemia caused by C. parapsilosis sensu stricto, C. metapsilosis or C. orthopsilosis. The currently used antifungal agents exhibited good in vitro activities against C. parapsilosis sensu lato species isolates.