Trends in direct oral anticoagulant use in patients presenting with acute stroke.

Acute ischaemic strokes occur despite the use of direct oral anticoagulants (DOACs). A retrospective review was conducted at a high-volume primary stroke centre over a 3-year period to assess the acute management of stroke presentations in patients prescribed DOACs. During the time period of the study, 103 of 195 anticoagulated stroke patients presented within the timeframe for thrombolysis and only 15 patients had DOAC plasma level assays performed. Of these 103, 5 received thrombolysis; however, DOAC level was not a factor in these cases.

Inconsistent idealizations and inferentialism about scientific representation.

Inferentialists about scientific representation hold that an apparatus's representing a target system consists in the apparatus allowing "surrogative inferences" about the target. I argue that a serious problem for inferentialism arises from the fact that many scientific theories and models contain internal inconsistencies. Inferentialism, left unamended, implies that inconsistent scientific models have unlimited representational power, since an inconsistency permits any conclusion to be inferred. I consider a number of ways that inferentialists can respond to this challenge before suggesting my own solution. I develop an analogy to exploitable glitches in a game. Even though inconsistent representational apparatuses may in some sense allow for contradictions to be generated within them, doing so violates the intended function of the apparatus's parts and hence violates representational "gameplay".

Cellular Immunotherapy for Hematologic Malignancies: Beyond Bone Marrow Transplantation.

Immunotherapy has changed treatment practices for many hematologic malignancies. Even in the current era of targeted therapy, chemotherapy remains the backbone of treatment for many hematologic malignancies, especially in acute leukemias, where relapse remains the major cause of mortality. Application of novel immunotherapies in hematology attempts to harness the killing power of the immune system against leukemia and lymphoma. Cellular immunotherapy is evolving rapidly for high-risk hematologic disorders. Recent advances include chimeric antigen-receptor T cells, mesenchymal stromal/stem cells, dendritic cell tumor vaccines, cytokine-induced killer cells, and virus-specific T cells. The advantages of nontransplantation cellular immunotherapy include suitability for patients for whom transplantation has failed or is contraindicated, and a potentially less-toxic treatment alternative to transplantation for relapsed/refractory patients. This review examines those emerging cellular immunotherapies that are changing treatment paradigms for patients with hematologic malignancies.

Diagnosis and treatment of MYH9-RD in an Australasian cohort with thrombocytopenia.

MYH9-related disorders (MYH9-RDs) caused by mutation of the MYH9 gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP). This may result in inappropriate treatment with corticosteroids, immunosupressants and in some cases, splenectomy. We explored the efficacy of next generation sequencing (NGS) with a candidate gene panel to establish the aetiology of thrombocytopenia for individuals who had been referred to our center from hematologists in the Australasian region in whom the cause of thrombocytopenia was suspected to be secondary to an inherited condition but which remained uncharacterized despite phenotypic investigations. Pathogenic MYH9 variants were detected in 15 (15/121, 12.4%) individuals and the pathogenecity of a novel variant of uncertain significance was confirmed in a further two related individuals following immunofluorescence (IF) staining performed in our laboratory. Concerningly, only one (1/17) individual diagnosed with MYH9-RD had been referred with this as a presumptive diagnosis, in all other cases (16/17, 94.1%), a diagnosis was not suspected by referring clinicians, indicating a lack of awareness or a failing of our diagnostic approach to these conditions. We examined the mean platelet diameter (MPD) measurements as a means to better identify and quantify platelet size. MPDs in cases with MYH9-RDs were significantly larger than controls (p < 0.001) and in 91% were greater than a previously suggested threshold for platelets in cases of ITP. In addition, we undertook IF staining in a proportion of cases and confirm that this test and/or NGS are satisfactory diagnostic tests. We propose that fewer cases of MYH9-RDs would be missed if diagnostic algorithms prioritized IF and/or NGS in cases of thrombocytopenia associated with giant platelets, even if döhle-like bodies are not appreciated on the peripheral blood film. Finally, our report describes the long-term use of a thrombopoietin agonist in a case of MYH9-RD that had previously been diagnosed as ITP, and demonstrates that treatment with these agents may be possible, and is well tolerated, in this group of patients.

Post-transitional adaptation of the left heart in uncomplicated, very preterm infants.

BACKGROUND: The postnatal period in preterm infants involves multiple physiological changes occurring immediately after birth and continuing for days or weeks. To recognise and treat compromise, it is important to measure cardiovascular function. The aim of this study was to describe longitudinal left ventricular function using conventional and novel echocardiography techniques in preterm infants who did not experience significant antenatal or postnatal complications and treatments. METHODS: We prospectively obtained cardiac ultrasound images at days 3, 7, 14, 21, and 28 in 25 uncomplicated, preterm infants <30 weeks of gestation. Speckle tracking analysis of the four chambers and short-axis images provided parameters of left ventricular volume, deformation, and basal myocardial velocities. The patent ductus arteriosus, cardiac dimensions, and atrial volume were also measured. RESULTS: Stroke volume increased by 24% during the study period (1.05-1.30 ml/kg, p<0.05). Cardiac length, diameter, and systolic basal myocardial velocity increased with unchanged wall stress and deformation parameters. Diastolic function parameters resembled that of the fetus with predominance of atrial contraction compared with early diastolic velocities. Blood pressure and estimates of left ventricular filing pressure increased, suggesting that left ventricular compliance did not change in this period. CONCLUSION: Stroke volume increased in the first 28 days after preterm birth. The preterm heart adapted by increasing its size, while maintaining systolic and atrial function, independent of early diastolic maturation. Longitudinal deformation of the left ventricle remained unchanged, suggesting relatively preserved function with maturation.

Cardiac Function After the Immediate Transitional Period in Very Preterm Infants Using Speckle Tracking Analysis.

BACKGROUND: The postnatal period in preterm infants involves multiple physiologic changes starting directly after birth and continuing for days or weeks. To recognize and treat compromise, it is important to measure cardiovascular function. We used a novel technique (speckle tracking echocardiography, STE) to measure cardiac function in this period. METHODS: We obtained cardiac ultrasound images at day 3, 7, 14, 21 and 28 in preterm infants <30-week gestation. Conventional measures included cardiac size, left ventricular stroke volume, atrial volume and the patent ductus arteriosus (PDA). Four chamber images were analyzed with STE, which provided parameters of left ventricular volume, longitudinal deformation and myocardial velocities. RESULTS: Images of 54 infants (gestational age 23-29 weeks) were analyzed. STE-derived stroke volume correlated well with conventional echocardiography-derived stroke volume, but agreement was suboptimal. Most STE parameters showed good reliability. All volume parameters and systolic and atrial velocities increased over time. Cardiac deformation and early diastolic velocity did not change. A PDA was associated with 33 % increased stroke volume at day 3 up to 98 % at day 28 with a spherically enlarged heart and increased filling pressure. CONCLUSION: Speckle tracking echocardiography analysis is a feasible and reliable technique that can simultaneously obtain systolic and diastolic volumes, longitudinal deformation and myocardial velocities from one ultrasound window. Preterm hearts maintain cardiac function well during the first weeks of life, even with increased preload as a consequence of a PDA.

Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia.

In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m(2) , days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age ≥60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50% at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.

Lenalidomide-based maintenance therapy reduces TNF receptor 2 on CD4 T cells and enhances immune effector function in acute myeloid leukemia patients.

A major limitation to improved outcomes in acute myelogenous leukemia (AML) is relapse resulting from leukemic cells that persist at clinical remission. Regulatory T cells (Tregs), which are increased in AML patients, can contribute to immune evasion by residual leukemic cells. Tumor necrosis factor (TNF), a pro-inflammatory cytokine present at high levels within patients, can induce TNF receptor-2 (TNFR2) expression on Tregs. We hypothesized that since TNFR2 is required for Treg stabilization and TNFR2+ Tregs are potent suppressors, targeting TNFR2+ Tregs may restore the effectiveness of immune-surveillance mechanisms. In this pilot study, we report AML patients in clinical remission have substantially increased levels of TNFR2+ T cells, including TNFR2+ Tregs and impaired effector CD4 T cell function with reduced IL-2 and IFNγ production. The immunomodulatory drug, lenalidomide, and the demethylating agent, azacitidine have been moderately successful in treating AML patients, but their combined effects on TNFR2+ T cells, including Tregs are currently unknown. Our data indicates that although treatment with lenalidomide and azacitidine increased cytokine production by effector T cells in all patients, durable clinical remissions may be observed in patients with a concomitant reduction in TNFR2+ T cells and TNFR2+ Tregs. In vitro studies further demonstrated that lenalidomide can reduce TNFR2 expression and can augment effector cytokine production by T cells, which can be further enhanced by azacitidine. These results indicate that reduction of TNFR2+ T cells in AML postremission phase may result from combined azacitidine/lenalidomide therapy and may contribute to an improved clinical outcome.

How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

Despite an increasing desire to use historical cohorts as "synthetic" controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012-2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

Factors that influence pain intensity and fentanyl requirements after a gynecologic laparotomy.

The association between pain intensity and its control by intravenous patient-controlled analgesia (IV-PCA) with fentanyl after a laparotomy for cystectomy/salphingoophorectomy, myomectomy, or hysterectomy was investigated. IV fentanyl infusion was administered to patients (n = 94) at 3 µg/kg/h to provide intraoperative analgesia after induction of general anesthesia. Postoperative fentanyl requirements were quantified via IV-PCA, and the amounts of rescue fentanyl required both during and after surgery were recorded. Mean values for PCA use as well as the visual analog scores (VAS) for pain were documented for up to 24 hours. The association between postoperative fentanyl requirements and VAS were then analyzed by using Mann-Whitney or Kruskal-Wallis tests. Patients with lower midline incisions had greater degrees of pain (p < .05) during the first 16 hours after surgery but did not consume more fentanyl compared with patients with Pfannenstiel incisions. Subjects who underwent operations lasting >4 hours required more rescue fentanyl during surgery (p < .05). However, this group consumed less fentanyl during the first 4 hours after surgery (p < .05). The demand at the fourth 4-hour period was lower among subjects undergoing myomectomy compared with cystectomy/salphingoophorectomy or hysterectomy (p = .045). Only a poor correlation was observed between pain intensity and analgesic usage. Postoperative pain intensity is influenced by the type of surgical incision but not the type of gynecologic surgery nor the duration of surgery. The relationship between subjective pain ratings with analgesic consumption is weak. Prolonged intraoperative administration of continuous IV fentanyl infusion may reduce fentanyl requirements in the immediate postoperative period.

Accuracy and Reliability of Smartphone Virtual Shade-Matching Technique: An In Vitro Study.

PURPOSE: To determine and compare the accuracy and reliability of shade matching using the conventional and smartphone virtual methods. MATERIALS AND METHODS: A phantom head with both maxillary central incisors removed was set up. A central incisor of various standard shades was inserted into the phantom head. Five undergraduate and five postgraduate students were asked to select the closest shade to match the central incisor using the Vita Classic shade guide. The procedure was then repeated using images taken by a smartphone. Each technique was repeated three times. Differences in accuracy of shade matching between the two techniques for every shade tab and between undergraduate and postgraduate dental students were compared using chi-square statistical analysis. The P value was set at .001. Differences in intra-rater and inter-rater reliability between the two techniques and among the three sessions were compared using paired t test and analysis of variance (ANOVA), respectively, with a P value of .05. The reliability of both techniques was further measured using Cohen kappa statistical test. RESULTS: The smartphone virtual shade-matching technique showed significantly higher accuracy in shade matching with most of the tested shade tabs than the conventional method (P < .001), irrespective of observers' clinical experience. Higher repeatability was found in the virtual technique than the conventional technique, with higher intra-rater and inter-rater reliability observed. CONCLUSION: Smartphone virtual shade matching showed better accuracy and reliability than the conventional method and could be used as an alternative shade-matching method.

Ultrasound-Guided Scalp Blocks for an Awake Craniotomy: A Case Report.

Ultrasound-guided scalp blocks may revolutionize regional anesthesia for neurosurgery. In this report, we demonstrate that ultrasound-guided scalp blocks can be used effectively for a craniotomy. A 48-year-old patient with a brain tumor at the motor cortex was scheduled for an awake craniotomy. Ultrasound-guided scalp blocks targeting the bilateral supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, greater auricular, lesser occipital, greater occipital, and third occipital nerves were performed. A total of 29 mL of levobupivacaine 0.3% was used. No additional local anesthetic agent was given for skull pinning, skin incision, or the craniotomy. Postoperatively, the patient remained pain-free, and she was discharged without complications.

Chronic Subdural Hematoma Drainage Under Local Anesthesia with Sedation versus General Anesthesia and Its Outcome.

BACKGROUND: Burr hole drainage is the criterion standard treatment for chronic subdural hematoma (CSDH), a common neurosurgical condition. However, apart from the surgical technique, the method of anesthesia also has a significant impact on postoperative patient outcome. Currently, there are limited studies comparing the use of local anesthesia with sedation (LA sedation) versus general anesthesia (GA) in the drainage of CSDH. The objective of this study was to compare the morbidity and mortality outcomes of using LA sedation versus GA in CSDH burr hole drainage. METHODS: This retrospective study presents a total of 257 operations in 243 patients from 2 hospitals. A total of 130 cases were operated under LA sedation in hospital 1 and 127 cases under GA in hospital 2. Patient demographics and presenting features were similar at baseline. RESULTS: Values are shown as LA sedation versus GA. Postoperatively, most patients recovered well in both groups with Glasgow Outcome Scale scores of 4-5 (96.2% vs. 88.2%, respectively). The postoperative morbidity was significantly increased by an odds ratio of 5.44 in the GA group compared with the LA sedation group (P = 0.005). The mortality was also significantly higher in the GA group (n = 5, 3.9%) than the LA sedation group (n = 0, 0.0%; P = 0.028). The CSDH recurrence rate was 4.6% in the LA sedation group versus 6.3% in the GA group. No intraoperative conversion from LA sedation to GA was reported. CONCLUSIONS: This study demonstrates that CSDH drainage under LA sedation is safe and efficacious, with a significantly lower risk of postoperative mortality and morbidity when compared with GA.

Evaluation of immature platelet fraction as a marker of dengue fever progression.

OBJECTIVES: Progression of dengue is often associated with thrombocytopenia resulting from viral-induced bone marrow suppression and immune-mediated peripheral platelet consumption. Immature platelet fraction (IPF), which can be measured using a haematology analyser, is a precursor indicating platelet formation in the bone marrow. This study evaluated the trend of IPF as an early recovery indicator of platelets in dengue patients with thrombocytopenia, and its relationship with severe dengue in conjunction with reticulocyte count. METHODS: Hospitalized patients with dengue were enrolled and followed-up daily until discharge. Blood investigations included daily full blood counts and IPF measured using a haematology analyser. RESULTS: In total, 287 patients with confirmed dengue were enrolled in this study, 25 of whom had severe dengue. All patients had a decreasing trend in platelet count in the first week of illness, concomitant with an increasing trend in the percentage of immature platelets to total platelets (IPF%) for more than 3 days prior to platelet recovery. IPF% was significantly increased in patients with severe dengue compared with patients with non-severe dengue on days 3-5 after the onset of fever. Reticulocyte count increased significantly in patients with severe dengue on day 5. CONCLUSIONS: IPF can be utilized as an early recovery indicator of platelets in patients with dengue and thrombocytopenia.

Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia.

PURPOSE: Ivosidenib is an oral inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, approved for treatment of IDH1-mutant (mIDH1) acute myeloid leukemia (AML). Preclinical work suggested that addition of azacitidine to ivosidenib enhances mIDH1 inhibition-related differentiation and apoptosis. PATIENTS AND METHODS: This was an open-label, multicenter, phase Ib trial comprising dose-finding and expansion stages to evaluate safety and efficacy of combining oral ivosidenib 500 mg once daily continuously with subcutaneous azacitidine 75 mg/m2 on days 1-7 in 28-day cycles in patients with newly diagnosed mIDH1 AML ineligible for intensive induction chemotherapy (ClinicalTrials.gov identifier: NCT02677922). RESULTS: Twenty-three patients received ivosidenib plus azacitidine (median age, 76 years; range, 61-88 years). Treatment-related grade ≥ 3 adverse events occurring in > 10% of patients were neutropenia (22%), anemia (13%), thrombocytopenia (13%), and electrocardiogram QT prolongation (13%). Adverse events of special interest included all-grade IDH differentiation syndrome (17%), all-grade electrocardiogram QT prolongation (26%), and grade ≥ 3 leukocytosis (9%). Median treatment duration was 15.1 months (range, 0.3-32.2 months); 10 patients remained on treatment as of February 19, 2019. The overall response rate was 78.3% (18/23 patients; 95% CI, 56.3% to 92.5%), and the complete remission rate was 60.9% (14/23 patients; 95% CI, 38.5% to 80.3%). With median follow-up of 16 months, median duration of response in responders had not been reached. The 12-month survival estimate was 82.0% (95% CI, 58.8% to 92.8%). mIDH1 clearance in bone marrow mononuclear cells by BEAMing (beads, emulsion, amplification, magnetics) digital polymerase chain reaction was seen in 10/14 patients (71.4%) achieving complete remission. CONCLUSION: Ivosidenib plus azacitidine was well tolerated, with an expected safety profile consistent with monotherapy with each agent. Responses were deep and durable, with most complete responders achieving mIDH1 mutation clearance.

Practice characteristics among dental anesthesia providers in the United States.

General descriptions or "snapshots" of sedation/general anesthesia practices during dental care are very limited in reviewed literature. The objective of this study was to determine commonalities in dental sedation/anesthesia practices, as well as to accumulate subjective information pertaining to sedation/anesthesia care within the dental profession. This questionnaire-based survey was completed by participating anesthesia providers in the United States. A standardized questionnaire was sent via facsimile, or was delivered by mail, to 1500 anesthesia providers from a randomized list using an online database. Data from the returned questionnaires were entered onto an Excel spreadsheet and were imported into a JMP Statistical Discovery Software program for analyses. Quantitative evaluations were confined to summation of variables, an estimation of means, and a valid percent for identified variables. A total of 717 questionnaires were entered for data analysis (N=717). Data from this study demonstrate the wide variation that exists in sedation/anesthesia care and those providing its administration during dental treatment in the United States. The demographics of this randomized population show anesthesia providers involved in all disciplines of the dental profession, as well as significant variation in the types of modalities used for sedation/anesthesia care. Data from this study reveal wide variation in sedation/anesthesia care during dental treatment. These distinctions include representation of sedation/anesthesia providers across all disciplines of the dental profession, as well as variations in the techniques used for sedation/anesthesia care.

Utility of directional high-density mapping catheter (AdvisorTM HD Grid) in complex scar-related atrial tachycardia.

Mapping of scar-related atrial tachycardias (AT) can be challenging even with the use of high-density (HD) mapping catheter. AdvisorTM HD Grid is the only directional HD mapping catheter which not only identify local electrical signal but more importantly capture the direction of wave front propagation especially in low voltage zone. Accordingly, we present a case of complex scar-related AT with the use of AdvisorTM HD Grid which showed clear fractionated signal at isthmus area as compare to the absence of signal on ablation catheter at the same area despite adequate contact force. Ablation at this area terminated the tachycardia.

Prospective assessment of the endometrium in postmenopausal breast cancer patients treated with fulvestrant.

This prospective study assessed the endometrial effects of fulvestrant, a pure estrogen-receptor antagonist, in postmenopausal women with breast cancer. This single-center study enrolled postmenopausal patients who had an intact uterus at baseline with progressive metastatic breast cancer on tamoxifen followed by an oral aromatase inhibitor (AI). Fulvestrant (250 mg) was administered every 28 +/- 3 days via IM injection. Transvaginal ultrasonography (TVUS) was performed at baseline and after 3 months of therapy. Primary and secondary endpoints were changes from baseline in double endometrial thickness (DET) and uterine volume (UV), respectively. No interventions were performed on any asymptomatic uterine abnormalities that were detected at baseline. In total, 32 women were enrolled. Five patients had no repeat TVUS because of early progression before 3 months, leaving 27 evaluable patients for final analysis. After 3 months therapy, mean DET had significantly decreased by 23.08% (P = 0.010). Mean UV also decreased by 10.88%, although this change was not significant (P = 0.119). After 3 months of therapy, none reported vaginal bleeding, there were no changes noted in most of the uterine pathologies present at baseline and no new uterine abnormalities were detected. We observed that 3 months of fulvestrant treatment resulted in a significant decrease in endometrial growth and a non-significant decrease in UV in postmenopausal women with metastatic breast cancer previously exposed to tamoxifen and AIs. Furthermore, no new uterine pathologies were detected, indicating that fulvestrant behaves as a pure antiestrogen at the uterine level.

Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors: Results from the Phase IIIb ENESTswift study.

BACKGROUND: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. METHODS: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. RESULTS: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid. CONCLUSION: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.