Decisive points for pregnancy losses in beef cattle.

Beef cattle producers rely on each of their cows to produce a marketable calf each year to maintain a sustainable operation. Within the first month of gestation, pregnancy failures have been recorded to be upwards of 40-50%. From fertilisation to birth, there are numerous factors contributing to pregnancy failure. From the beginning of gestation oocyte competence is often a large factor impacting fertility as the dam contributes all mRNA for initial embryo development. Other factors contributing to early embryonic infertility include hormonal concentration and heat stress. After the embryo enters the uterus, it becomes critical for the uterus to be receptive to the developing conceptus. The embryo then begins to elongate and secrete interferon-tau to initiate maternal recognition of pregnancy; a requirement to establish and maintain bovine pregnancies. After a pregnancy completes these steps, placentation actively begins around day 22 of pregnancy and lasts until organogenesis. The fetal phase follows the embryonic phase where disease and/or toxins are often the cause of pregnancy failure at this period. However, fetal mortality has been reported to occur in less than 10% of pregnancies. Understanding of the many factors influencing infertility needs to be further investigated to increase pregnancy success in beef cattle.

Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Serine protease inhibitor-6 differentially affects the survival of effector and memory alloreactive CD8-T cells.

The clonal expansion of effector T cells and subsequent generation of memory T cells are critical in determining the outcome of transplantation. While cytotoxic T lymphocytes induce direct cytolysis of target cells through secretion of Granzyme-B (GrB), they also express cytoplasmic serine protease inhibitor-6 (Spi6) to protect themselves from GrB that has leaked from granules. Here, we studied the role of GrB/Spi6 axis in determining clonal expansion of alloreactive CD8-T cells and subsequent generation of memory CD8-T cells in transplantation. CD8-T cells from Spi6(-/-) mice underwent more GrB mediated apoptosis upon alloantigen stimulation in vitro and in vivo following adoptive transfer into an allogeneic host. Interestingly, while OT1.Spi6(-/-) CD8 T cells showed significantly lower clonal expansion following skin transplants from OVA mice, there was no difference in the size of the effector memory CD8-T cells long after transplantation. Furthermore, lack of Spi6 resulted in a decrease of short-lived-effector-CD8-cells but did not impact the pool of memory-precursor-effector-CD8-cells. Similar results were found in heart transplant models. Our findings suggest that the final alloreactive CD8-memory-pool-size is independent from the initial clonal-proliferation as memory precursors express low levels of GrB and therefore are independent of Spi6 for survival. These data advance our understanding of memory T cells generation in transplantation and provide basis for Spi6 based strategies to target effector T cells.

Evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for adjuvant radiotherapy in breast cancer.

BACKGROUND: The European Society of Medical Oncology (ESMO) has suggested using the ESMO-Magnitude of Clinical Benefit Scale (MCBS) to grade the magnitude of clinical benefit of cancer therapies. This approach has not been applied to radiation therapy (RT) yet. We applied the ESMO-MCBS to experiences describing the use of RT to assess (1) the 'scoreability' of the data, (2) evaluate the reasonableness of the grades for clinical benefit and (3) identify potential shortcomings in the current version of the ESMO-MCBS in its applicability to RT. MATERIALS AND METHODS: We applied the ESMO-MCBS v1.1 to a selection of studies in radiotherapy that had been identified as references in the development of American Society for Radiation Oncology (ASTRO) evidence-based guidelines on whole breast radiation. Of the 112 cited references, we identified a subset of 16 studies that are amenable to grading using the ESMO-MCBS. RESULTS: Of the 16 studies reviewed, 3/16 were scoreable with the ESMO tool. Six of 16 studies could not be scored because of shortcomings in the ESMO-MCBS v1.1: (1) in 'non-inferiority studies', there is no credit for improved patient convenience, reduced patient burden or improved cosmesis; (2) in 'superiority studies' evaluating local control as a primary endpoint, there is no credit for the clinical benefit such as reduced need for further interventions. In 7/16 studies, methodological deficiencies in the conduct and reporting were identified. CONCLUSIONS: This study represents a first step in determining the utility of the ESMO-MCBS in the evaluation of clinical benefit in radiotherapy. Important shortcomings were identified that would need to be addressed in developing a version of the ESMO-MCBS that can be robustly applied to radiotherapy treatments. Optimization of the ESMO-MCBS instrument will proceed to enable assessment of value in radiotherapy.

Arsenic toxicity in a sediment-dwelling polychaete: detoxification and arsenic metabolism.

The accumulation, subcellular distribution and speciation of arsenic in the polychaete Arenicola marina were investigated under different laboratory exposure conditions representing a range of metal bioavailabilities, to gain an insight into the physiological mechanisms of how A. marina handles bioaccumulated arsenic and to improve our understanding of the potential ecotoxicological significance of bioaccumulated arsenic in this deposit-feeder. The exposure conditions included exposure to sublethal concentrations of dissolved arsenate, exposure to sublethal concentrations of sediment-bound metal mining mixtures, and exposure to lethal concentrations of sediment-bound metal mining mixtures and arsenic- and multiple metal-spiked sediments. The sub-lethal exposures indicate that arsenic bioaccumulated by the deposit-feeding polychaete A. marina is stored in the cytosol as heat stable proteins (~50%) including metallothioneins, possibly as As (III)-thiol complexes. The remaining arsenic is mainly accumulated in the fraction containing cellular debris (~20%), with decreasing proportions accumulated in the metal-rich granules, organelles and heat-sensitive proteins fractions. A biological detoxified metal compartment including heat stable proteins and the fraction containing metal-rich granules is capable of binding arsenic coming into the cells at a constant rate under sublethal arsenic bioavailabilities. The remaining arsenic entering the cell is bound loosely into the cellular debris fraction, which can be subsequently released and diverted to an expanding detoxified pool. Our results suggest that a metal sensitive compartment comprising the cellular debris, enzymes and organelles fractions may be more representative of the toxic effects observed.

Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting.

Approximately 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.; most are not aware of their infection. Our objectives were to examine HCV testing practices to determine which patient characteristics are associated with HCV testing and positivity, and to estimate the prevalence of HCV infection in a high-risk urban population. The study subjects were all patients included in the baseline phase of the Hepatitis C Assessment and Testing Project (HepCAT), a serial cross-sectional study of HCV screening strategies. We examined all patients with a clinic visit to Montefiore Medical Center from 1/1/08 to 2/29/08. Demographic information, laboratory data and ICD-9 diagnostic codes from 3/1/97-2/29/08 were extracted from the electronic medical record. Risk factors for HCV were defined based on birth date, ICD-9 codes and laboratory data. The prevalence of HCV infection was estimated assuming that untested subjects would test positive at the same rate as tested subjects, based on risk-factors. Of 9579 subjects examined, 3803 (39.7%) had been tested for HCV and 438 (11.5%) were positive. The overall prevalence of HCV infection was estimated to be 7.7%. Risk factors associated with being tested and anti-HCV positivity included: born in the high-prevalence birth-cohort (1945-64), substance abuse, HIV infection, alcohol abuse, diagnosis of cirrhosis, end-stage renal disease, and alanine transaminase elevation. In a high-risk urban population, a significant proportion of patients were tested for HCV and the prevalence of HCV infection was high. Physicians appear to use a risk-based screening strategy to identify HCV infection.

"Bridge population": sex workers or their clients?--STI prevalence and risk behaviors of clients of female sex workers in China.

As the HIV/AIDS epidemic and the spread of sexually transmitted infections (STIs) in China has come to the forefront of public health attention, female sex workers (FSWs) and their clients (CFSWs) are becoming increasingly important to HIV/STI prevention efforts. This secondary analysis uses data abstracted from the Chinese Health and Family Life Survey 1999-2000 to report prevalence rates of two STIs as well as sexual risk behaviors for CFSWs - men who paid for sex with FSWs in the past 12 months - in comparison with men who had not patronized FSWs. Among 1879 Chinese CFSWs who completed anonymous interviews and urine testing, 152 (6.3%, weighted) said they had paid for sex in the past 12 months and 18.8% of CFSWs (weighted) tested positive for gonorrhea. CFSWs were 10 times more likely to have an STI (either self-reported or tested) than non-client Chinese men, and they were equally likely to use condoms inconsistently with their spouses. This study highlights the importance of studying CFSWs who use condoms inconsistently and do not practice safe sex with their spouse as a potential bridge population. Prevention and intervention efforts should target this bridge population and include education on HIV/AIDS and STI transmission, condom promotion, marriage counseling, destigmatization of HIV and STIs, and promotion of STI diagnosis and treatment.

An assessment of the current status of children's toothpaste in Australia.

BACKGROUND: Despite recommendations that pre-school children use toothpaste containing 500-550 ppm of fluoride, there has been an increase in non-fluoridated toothpastes marketed for children. This study investigated children's toothpaste in Australia. METHODS: A comprehensive audit of all toothpastes marketed for pre-school children and available in store in the Macarthur region of NSW, Australia, was carried out. All toothpastes available for purchase were obtained and examined; size and price were catalogued, along with ingredient lists and fluoride levels. RESULTS: One hundred and seven individual toothpastes were identified in the audit, with 67 (62.6%) containing no fluoride. Of the 40 fluoridated toothpastes, only 11 (10.3%) contained the recommended level of fluoride of 500-550 ppm. Twenty-two (20.6%) of all toothpastes were made in Australia, all of which were non-fluoridated. Six (5.6%) of the toothpastes studied contained excessive levels of fluoride (1350-1500 ppm). Seventeen of the 20 least expensive toothpastes contained fluoride, while 18 of the 20 most expensive toothpastes were non-fluoridated. CONCLUSIONS: Despite expert recommendations, the majority of children's toothpaste available in Australia contains either no fluoride or the wrong levels of fluoride. Further study is needed to determine why this change is occurring and what is influencing the increase in non-fluoride toothpastes on the market.

Prevalence and risks for sexually transmitted infections among a national sample of migrants versus non-migrants in China.

This study aims to describe and compare the gender-specific prevalence of chlamydia and gonorrhoea, sexual behaviours and experiences, and risk factors associated with sexually transmitted infections (STIs) among migrants versus rural and urban non-migrants in China. Data were abstracted from the Chinese Health and Family Life Survey conducted from 1999 to 2000, which provided a nationally representative adult (ages 20-64 years) sample. STI results were determined using a urine-based nucleic acid amplification assay. The prevalence of chlamydia for migrant women was triple that of rural non-migrant women. Migrants were more likely to engage in STI-associated risk behaviours than non-migrants (e.g. receiving money for sex). Among migrants, women were more likely than men to have STIs. The high STI prevalence among migrants highlights an urgent need to implement comprehensive prevention and intervention programmes targeting the cultural, social and structural needs of migrants in the city, especially migrant women.

Key residues controlling binding of diverse ligands to human cytochrome P450 2A enzymes.

Although the human lung cytochrome P450 2A13 (CYP2A13) and its liver counterpart cytochrome P450 2A6 (CYP2A6) are 94% identical in amino acid sequence, they metabolize a number of substrates with substantially different efficiencies. To determine differences in binding for a diverse set of cytochrome P450 2A ligands, we have measured the spectral binding affinities (K(D)) for nicotine, phenethyl isothiocyanate (PEITC), coumarin, 2'-methoxyacetophenone (MAP), and 8-methoxypsoralen. The differences in the K(D) values for CYP2A6 versus CYP2A13 ranged from 74-fold for 2'-methoxyacetophenone to 1.1-fold for coumarin, with CYP2A13 demonstrating the higher affinity. To identify active site amino acids responsible for the differences in binding of MAP, PEITC, and coumarin, 10 CYP2A13 mutant proteins were generated in which individual amino acids from the CYP2A6 active site were substituted into CYP2A13 at the corresponding position. Titrations revealed that substitutions at positions 208, 300, and 301 individually had the largest effects on ligand binding. The collective relevance of these amino acids to differential ligand selectivity was verified by evaluating binding to CYP2A6 mutant enzymes that incorporate several of the CYP2A13 amino acids at these positions. Inclusion of four CYP2A13 amino acids resulted in a CYP2A6 mutant protein (I208S/I300F/G301A/S369G) with binding affinities for MAP and PEITC much more similar to those observed for CYP2A13 than to those for CYP2A6 without altering coumarin binding. The structure-based quantitative structure-activity relationship analysis using COMBINE successfully modeled the observed mutant-ligand trends and emphasized steric roles for active site residues including four substituted amino acids and an adjacent conserved Leu(370).

Chenopodium as a prehistoric domesticate in eastern north america: evidence from russell cave, alabama.

Approximately 50,000 carbonized fruits of the species Chenopodium berlandieri recovered from Russell Cave, Alabama, and dating to 1975 +/- 55 before the present, exhibit a set of interrelated morphological characteristics reflecting domestication (thin testa, truncate margin, rectanguloid fruit cross section, ligulate cotyledons, and increased internal fruit volume). These morphological characteristics establish the presence of a domestic variety of Chenopodium in the eastern United States by 2000 years ago.

Origins of agriculture in eastern north america.

As a result of research carried out over the past decade, eastern North America now provides one of the most detailed records of the origins of agriculture available. Spanning a filll three millennia, the transition from forager to farmer in eastern North America involved the domestication of four North American seed plants during the second millennium B.C., the initial emergence of food production economies based on local crop plants between 250 B.C. and A.D. 200, and the rapid and broad-scale shift to maize-centered agriculture during the three centuries from A.D. 800 to 1100.

The effect of surface charge, negative and bipolar ionization on the deposition of airborne bacteria.

AIMS: A series of experiments were conducted to evaluate the effect of surface charge and air ionization on the deposition of airborne bacteria. METHODS AND RESULTS: The interaction between surface electrostatic potential and the deposition of airborne bacteria in an indoor environment was investigated using settle plates charged with electric potentials of 0, +/-2.5kV and +/-5kV. Results showed that bacterial deposition on the plates increased proportionally with increased potential to over twice the gravitational sedimentation rate at +5kV. Experiments were repeated under similar conditions in the presence of either negative or bipolar air ionization. Bipolar air ionization resulted in reduction of bacterial deposition onto the charged surfaces to levels nearly equal to gravitational sedimentation. In contrast, diffusion charging appears to have occurred during negative air ionization, resulting in an even greater deposition onto the oppositely charged surface than observed without ionization. CONCLUSIONS: Static charges on fomitic surfaces may attract bacteria resulting in deposition in excess of that expected by gravitational sedimentation or simple diffusion. Implementation of bipolar ionization may result in reduction of bacterial deposition. SIGNIFICANCE AND IMPACT OF STUDY: Fomitic surfaces are important vehicles for the transmission of infectious organisms. This study has demonstrated a simple strategy for minimizing charge related deposition of bacteria on surfaces.

The sandhopper Talitrus saltator (Crustacea: Amphipoda) as a biomonitor of trace metal bioavailabilities in European coastal waters.

The amphipod crustacean Talitrus saltator is an established, easily accessible, biomonitor of trace metal bioavailabilities in coastal waters. We have carried out a geographically widespread collection of T. saltator from European shores, stretching from the north-west Atlantic through the Baltic to the Mediterranean. A primary aim of the work was to establish a database of accumulated trace metal concentrations (Cd, Cr, Cu, Fe, Mn and Zn) in this biomonitor. Statistical analysis has shown significant geographical differences in the bioavailabilities of all the metals, the most distinct being copper, iron and manganese. It has proved possible to identify unusually high accumulated concentrations of Cd, Cr, Cu, Fe, Mn and Zn in this biomonitor, indicative of high metal bioavailability at a particular site. These may serve as reference points for future biomonitoring programmes seeking to identify metal contamination in coastal waters.

Acute bilineal leukemia: a rare disease with poor outcome.

Most cases of acute leukemia can be assigned to the myeloid, B or T lineage. In a few cases, definitive assignment cannot be achieved because blasts express antigens of more than one lineage. A subset of these, referred to as acute bilineal leukemias (aBLLs), is characterized by the presence of more than one population of blasts, each comprising a single lineage. We identified 19 cases of aBLL, including 10 mixed T and myeloid (T-My) and nine mixed B and myeloid (B-My); no mixed B and T cases were identified. Cytogenetic data were available for 16 patients. Three of seven patients with B-My had a t(9;22)(q34q11.2), two had 11q23 translocations and one had del(9). Two of nine patients with T-My had 2p13 translocations; five had other unrelated abnormalities. Of 16 patients with outcome data, only six achieved complete remission and only two remain free of disease 2.5 and 4.5 years after chemotherapy or stem cell transplantation. aBLL is a rare disease that combines B or T and myeloid blasts. Cytogenetic abnormalities of t(9;22) and 11q23 are common in, and may be restricted to, B-My cases, while T-My cases have frequent but generally non-recurring abnormalities. Both types of aBLL are associated with poor outcome.

Induction of acute lymphocytic leukemia differentiation by maintenance therapy.

Despite extensive study in many malignancies, maintenance therapy has clinically benefited only two diseases: acute lymphocytic leukemia (ALL) and acute promyelocytic leukemia (APL). ALL maintenance therapy utilizes low-dose 6-mercaptopurine (6MP) and methotrexate (MTX), while maintenance in APL primarily consists of all-trans-retinoic acid (ATRA). 6MP and MTX as used in ALL are also now usually added to maintenance ATRA for APL, based on data suggesting an improved disease-free survival. Although the mechanism of action of MTX and 6MP as maintenance is unknown, low-dose cytotoxic agents are potent inducers of differentiation in vitro. Thus, we studied whether maintenance therapy in ALL, like ATRA in APL, may be inducing terminal differentiation of ALL progenitors. The APL cell line NB4, the ALL cell lines REH and RS4;11, and patients' ALL blasts were incubated with ATRA, 6MP, and MTX in vitro. All three drugs inhibited the clonogenic growth of the APL and ALL cell lines without inducing immediate apoptosis, but associated with induction of phenotypic differentiation. The three drugs similarly upregulated lymphoid antigen expression, while decreasing CD34 expression, on patients' ALL blasts. These data suggest that induction of leukemia progenitor differentiation plays an important role in the mechanism of action of maintenance therapy in ALL.

Quantitative analysis of bone marrow CD34 cells in aplastic anemia and hypoplastic myelodysplastic syndromes.

Aplastic anemia (AA) and hypoplastic myelodysplastic syndromes (hMDS) are often difficult to distinguish. However, an accurate diagnosis is important because the prognosis and treatment of these diseases may differ. CD34+ hematopoietic progenitors are central to the pathogenesis of both disorders; they are the targets of the autoimmune attack in AA and neoplastic transformation in MDS. The aim of this study was to assess whether bone marrow CD34+ cell numbers could be used in differentiating between AA and hMDS. The percentage of bone marrow CD34+ cells was normal or increased (mean -3.5+0.5%, range 1-7%) in 15 of 35 patients studied, and low (mean -0.13 +/- 0.02%, range 0.02-0.36%) in 20 of 35 patients. All patients with a normal or increased percentage of CD34+ cells were ultimately diagnosed with hMDS based on the detection of clonal cytogenetic abnormalities or progression to refractory anemia with excess blasts/acute myeloid leukemia. All patients with low marrow CD34+ cell numbers met standard clinical criteria for AA and have not demonstrated neoplastic transformation with follow-up. Quantification of marrow CD34+ cells may serve as an important tool for distinguishing between AA and hMDS.

Butyltins, trace metals and morphological variables in surf scoter (Melanitta perspicillata) wintering on the south coast of British Columbia, Canada.

From 1998 to 2001 we examined spatial and temporal variation in uptake of contaminants by surf scoters (Melanitta perspicillata) in the Georgia Basin region of the Pacific coast of Canada. Samples were collected during late fall and early spring at industrialized and reference locations, carcasses examined, and tissues collected for histology, biomarkers, and contaminant analyses. Scoters from both Vancouver and Victoria harbours had significantly higher hepatic concentrations of summation operatorbutyltins than birds from a reference site. In adult male surf scoters, hepatic summation operatorbutyltins increased over the winter at two sites (p=0.02, n=26), while mercury increased (p=0.03, n=15) and selenium decreased at one site (p=0.001, n=15). Body condition decreased over the winter at both the treatment site, Howe Sound (p<0.0001, n=12), and the reference site, Baynes Sound (p=0.02, n=15). Multiple regression analysis using Akaike's Information Criteria (AIC(C)) showed an association between hepatic butyltin concentrations and overall body condition (p=0.06, r=-0.237).

Impact of urologists' ownership of radiation equipment in the treatment of prostate cancer.

BACKGROUND: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. We wanted to evaluate how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referral practice (SRP) compared to a traditional urologic practice. METHODS: A total of 17 982 men aged 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. A total of 13 SRPs in the state of Texas were evaluated. We used multilevel logistic regression models that evaluated the odds of receiving a specific type of treatment. RESULTS: Men diagnosed in SRPs were more likely to receive upfront treatment (vs watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs 89%; adjusted odds ratio (AOR) 1.61, 95% confidence interval (CI) 1.30-2.00; P<0.001) and were more likely to be treated with external beam radiation (47.4% vs 34.1%; AOR 1.59, 95% CI 1.37-1.84; P<0.001). This persisted for both favorable and unfavorable risk cancer. Median annual prostate cancer care cost was $2460 (95% CI $1663-$3368) higher for men diagnosed by SRPs. Limitations include data limited to men aged 65 years or older and geographic concentration of SRPs in Texas may not depict nationwide patterns. CONCLUSIONS: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.

Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide.

Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.