Hits 1 - 10 (out of 6027 matching entities) [11178 mentions] (33 ms):
1. chronic myeloid leukemias

9244 articles, score 4339.433

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Enriched GO Terms

Abstracts

  • Smoking is suspected to not only be a risk factor for chronic myeloid leukemia but an adverse prognostic factor for the disease as well. The objective of the current study was to investigate the impact of smoking on survival and progression to advanced phases of disease. Based on the data of the German CML Study IV, the authors analyzed the effect of smoking using a multivariate Cox model with the addition of the European Treatment and Outcome Study (EUTOS) long-term survival score variables of age, spleen size, thrombocytes, and peripheral blasts as well as sex, comorbidities, and type of treatment center. The 8-year survival probability was 87% for a nonsmoking patient and 83% for a patient who smoked. The authors noted a 2.08-times higher risk of death for smokers in comparison with nonsmokers and a 2.11-times higher cause-specific hazard of disease progression. An interaction between smoking and age was found in the model for survival. No significant difference with regard to molecular response was observed. Even when considering differences in socioeconomic status and lifestyle between patients who smoke and nonsmokers, the current analysis demonstrated that smoking also might affect disease biology. The results of the current study indicate that patients with chronic myeloid leukemia, in particular those aged <60 years, should be encouraged to quit smoking. Cancer 2017;123:2467-71. © 2017 American Cancer Society.
    Smokers with chronic myeloid leukemia are at a higher risk of disease progression and premature death.
    Cancer, Jul 2017 [PubMed 28192602]
  • Medication adherence is a major issue for patients with a chronic illness, who sometimes rationally choose temporary nonadherence. This study aims at better understanding intentional nonadherence and especially why it seems to fluctuate over time. It is based on 48 semi-structured interviews conducted in a hospital in the Netherlands with patients who had been prescribed a medication for a chronic disease for at least 1 year, and who had either type 2 diabetes, hypertension, Parkinson's disease, inflammatory bowel disease, or chronic myeloid leukemia. The analysis uses a simplified version of the failure modes and effects analysis (FMEA) method. Intentional nonadherence appeared to be the result of the respondents' desire (a) to exert control over the treatment and its effects on their body, and (b) to control the hold of the treatment on their daily life. This result provides a rationale for the fluctuation of intentional nonadherence behavior.
    Intentional Nonadherence as a Means to Exert Control.
    Qualitative health research, Jul 2017 [PubMed 28682739]
  • Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; 37 patients carried mutations. Sixteen of these had evidence of mutations originating from preleukemic clones. Using unsupervised hierarchical clustering, we identified 5 distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy. This study demonstrates that patterns of mutation acquisition, persistence, and clearance vary but have a number of interesting correlations with clinical outcomes. Mutation burden often persisted despite successful TKI response (pattern 1), providing indirect evidence that these mutations also originated from preleukemic mutations, whereas patients exhibiting mutation clearance (pattern 3) showed mixed clinical outcomes. Unsurprisingly, patients acquiring new mutations during treatment failed TKI therapy (pattern 2). These patterns show that CML mutation dynamics following TKI therapy are markedly distinct from other myeloid neoplasms. In summary, clinical implications of mutation profiles and dynamics in CML should be interpreted with caution.
    Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy.
    Blood, Jan 2017 [PubMed 27733357]

2. imatinib

3043 articles, score 1358.852

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Enriched GO Terms

Abstracts

  • We conducted this study to identify the factors for predicting poor outcomes in chronic myeloid leukemia patients who failed to achieve a 3-month early molecular response (EMR). Of the 413 newly diagnosed, chronic phase, chronic myeloid leukemia patients receiving imatinib (IM), 120 (29.1%) failed to achieve a 3-month EMR. With a median follow-up of 67.0 months, 39 patients continued IM treatment with at least complete cytogenetic response (CCyR), and 81 patients permanently discontinued IM treatment. The cumulative incidence rates of CCyR and major molecular response (MMR) by 3 years were 90.1 ± 3.9% and 53.7 ± 7.3%, respectively. After adjusting for potential factors, multivariate analyses showed that a transcript type of e13a2, compared with e14a2, and a larger spleen size were independent factors for failure of overall MMR. The predictive factors outlined in this study may provide valuable information for high-risk patients who would benefit from early decision-making regarding therapy change.
    Baseline BCR-ABL1 transcript type of e13a2 and large spleen size are predictors of poor long-term outcomes in chronic phase chronic myeloid leukemia patients who failed to achieve an early molecular response after 3 months of imatinib therapy.
    Leukemia & lymphoma, May 2017 [PubMed 28540759]
  • The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine-kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine-kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials with imatinib first-line. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow-up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to second primary malignancies diagnosis was 34 months. We did not find a higher incidence of second primary malignancies compared to the age- and sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% C.I. 0.57-1.54) and 1.61 (95% C.I. 0.92-2.31) in males and females, respectively. Overall, 3.1% patients died for second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to what expected in the age- and sex-matched Italian population, with standardized mortality ratio of 2.41 (95% C.I. 1.26 - 3.56). In conclusion, our analysis of imatinib-treated chronic myeloid leukemia patients did not disclose a higher incidence of second primary malignancies; however, second primary malignancies outcome was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926.
    Incidence of second primary malignancies and related mortality in imatinib-treated chronic myeloid leukemia patients.
    Haematologica, Jun 2017 [PubMed 28572163]
  • In the last decade, the use of imatinib has brought a paradigm shift in the management of chronic myeloid leukemia (CML). In India, imatinib has been available for more than a decade and has been made accessible to all segments of the population because of patient assistance programs and cheaper generic versions. Despite improvements in survival, there are unique challenges in the Indian context. We reviewed published data pertaining to CML in India for the period of 1990 to 2016, using PubMed advanced search with the terms chronic myeloid leukemia and India, and included studies that reported on epidemiology, monitoring for therapy, treatment outcomes, and resistance. Additionally, the references in retrieved articles were also reviewed. Thirty-seven studies were identified. The incidence of CML may be slightly lower in India than in the West, but there was only a single article reporting population-based data. Indian patients presented with more advanced disease. Most centers have access to imatinib as first-line therapy, but there is limited availability of molecular monitoring and second-line therapy. Most of the outcome data were retrospective but seemed comparable with that reported in Western centers. Drug adherence was impaired in at least one third of patients and contributed to poor survival. Focused prospective studies and cooperative studies might improve the quality of data available. Future studies should focus on adherence, its effects on outcomes, and methods to address this problem.
    Chronic Myeloid Leukemia in India.
    Journal of global oncology, Feb 2017 [PubMed 28717743]

3. acute myeloid leukemias

2607 articles, score 1084.975

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Enriched GO Terms

Abstracts

  • Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis. The pseudo-observations can be used as a replacement of the outcomes without censoring when applying 'standard' causal inference methods, such as (1) or (2) earlier. We study this idea for estimating the average causal effect of a binary treatment on the survival probability, the restricted mean lifetime, and the cumulative incidence in a competing risks situation. The methods will be illustrated in a small simulation study and via a study of patients with acute myeloid leukemia who received either myeloablative or non-myeloablative conditioning before allogeneic hematopoetic cell transplantation. We will estimate the average causal effect of the conditioning regime on outcomes such as the 3-year overall survival probability and the 3-year risk of chronic graft-versus-host disease. Copyright © 2017 John Wiley & Sons, Ltd.
    Causal inference in survival analysis using pseudo-observations.
    Statistics in medicine, Jul 2017 [PubMed 28384840]
  • Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.
    Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.
    Journal of the Pediatric Infectious Diseases Society, May 2017 [PubMed 28549148]
  • Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy option for children with acute myeloid leukemia (AML) resistant to the first course of induction chemotherapy (IC1st). We aimed to identify the efficacy of unmanipulated haploidentical HSCT (haplo-HSCT) in children with AML in the first complete remission and whether children resistant (IC1st-resistant; n = 38) or sensitive (IC1st-sensitive; n = 59) to the IC1st can achieve comparable outcomes. The cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) and severe chronic GVHD was .0% versus 20.1% (P = .038) and 21.7% versus 13.2% (P = .238), respectively, for the IC1st-resistant and IC1st-sensitive groups. The 3-year cumulative incidence of relapse and nonrelapse mortality was 22.2% versus 7.6% (P = .061) and 5.3% versus 10.8% (P = .364), respectively, for the IC1st-resistant and IC1st-sensitive groups. The 3-year probability of overall survival and disease-free survival was 76.3% versus 83.0% (P = .657) and 72.5% versus 81.6% (P = .396), respectively, for the IC1st-resistant and IC1st-sensitive groups. Multivariate analysis failed to show significant differences in survival rates between the groups. Thus, our results show that unmanipulated haplo-HSCT may overcome the poor prognostic significance of IC1st-resistance in children with AML, and it is valid as a postremission treatment for children with IC1st-resistant AML lacking an HLA-matched donor.
    Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation in First Complete Remission Can Abrogate the Poor Outcomes of Children with Acute Myeloid Leukemia Resistant to the First Course of Induction Chemotherapy.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Dec 2016 [PubMed 27614057]

4. BCR

2659 articles, score 1029.853

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Enriched GO Terms

Abstracts

  • The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.
    BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, Jan 2017 [PubMed 28580869]
  • Molecular monitoring of BCR-ABL1 transcript levels using quantitative polymerase chain reaction is an essential part of the modern management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Establishing the diagnostic BCR-ABL1 fusion transcript is necessary in order to select appropriate primers and probes for such monitoring. A case is described in which quantitative polymerase chain reaction failed to detect the presence of BCR-ABL1 fusion transcript in a Philadelphia chromosome-positive chronic myeloid leukemia patient. Further investigation demonstrated a novel in-frame BCR-ABL1 fusion transcript with a breakpoint in BCR exon 13 and insertion of a sequence of ABL1 intron 1, therefore enabling subsequent molecular monitoring. This case highlights the requirement for characterization of the BCR-ABL1 transcript type at chronic myeloid leukemia diagnosis. Issues concerning standardized methodological approaches and interpretation of transcript levels in such rare cases are discussed.
    Characterization of a novel variant BCR-ABL1 fusion transcript in a patient with chronic myeloid leukemia: Implications for molecular monitoring.
    Hematology/oncology and stem cell therapy, Jun 2017 [PubMed 27013275]
  • Chronic myeloid leukemia treatment monitoring using polymerase chain reaction-based peripheral blood testing of t9;22 BCR-ABL1 provides improved test sensitivity over cytology but suffers from inadequate standardization in most laboratories due to variations inherent in the existing polymerase chain reaction methodologies. We performed the initial analytic performance evaluation of a novel competitive template-based peripheral blood b2a2/b3a2 transcript abundance method, called standardized nucleic acid quantification (SNAQ) test, with hypothesis that this will produced more consistent results with less frequent interlaboratory variations. Thirty-six chronic myeloid leukemia patients treated at our institution were enrolled. We compared SNAQ test with 2 laboratory developed test at the MD Anderson molecular diagnostic laboratory and Cancer Genetics Institute for analyzing BCR-ABL1 from peripheral blood samples. Each test result (n=36) was ranked against all the other samples tested by the same method. The Pearson correlation between SNAQ and laboratory developed test done at 2 labs was met by correlations of 0.97, 0.96, 0.96, and 0.94. Analysis of variance of log %BCR-ABL1 interlaboratory results indicated no significant difference (P=0.98). Post hoc analysis of method agreement showed the SNAQ method had a 95% limit of agreement of ±3-fold between laboratories. In this pilot study, SNAQ methodology performed consistent with half-log accuracy. Additional studies from a larger sample size and correlation with clinical outcomes are required to confirm this observation.
    New Tool for Monitoring Molecular Response in Patients With Chronic Myeloid Leukemia.
    Applied immunohistochemistry & molecular morphology : AIMM, Jul 2017 [PubMed 28682832]

5. leukemias

2603 articles, score 1022.718

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Enriched GO Terms

Abstracts

  • It was studied that cancer-causing processes are related with the disproportions of essential and toxic elements in body tissues and fluid. The purpose of the current study was to evaluate the levels of magnesium (Mg) and cadmium (Cd) in serum and blood samples of smokers and nonsmokers who have chronic myeloid (CML) and lymphocytic (CLL) leukemia, age ranged 31-50 years. For comparative study, age-matched smokers and nonsmoker males were chosen as controls/referents. The levels of elements in patient were analyzed before any treatment by atomic absorption spectrophotometer, after microwave assisted acid digestion. The validation of the method was done by using certified reference materials of serum and blood samples. The resulted data indicated that the adult male smokers and nonsmokers have two- to fourfold higher levels of Cd in the blood and sera samples as compared to the referents (p < 0.01), whereas two- to threefold lower levels of Mg was found in blood and serum samples of both types of leukemia patients as related to referent values. The resulted data indicates significant negative correlation among Mg and Cd in leukemia patients and smoker referents. Further studies are needed to clarify the role of these elements in pathogenesis of chronic leukemia.
    Correlation of Cadmium and Magnesium in the Blood and Serum Samples of Smokers and Non-Smokers Chronic Leukemia Patients.
    Biological trace element research, Mar 2017 [PubMed 27511371]
  • A dynamic modeling approach to the risk assessment of radiogenic myeloid leukemia is proposed. A basic tool of this approach is a biologically motivated mathematical model of the granulocytopoietic system, which is capable of predicting the dynamics of blood granulocytes and bone marrow granulocytopoietic cells in acutely and chronically irradiated humans. The performed modeling studies revealed that the dose dependence of the scaled maximal concentration of bone marrow granulocytopoietic cells with radiation-induced changes, which make a cell premalignant, and the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to acute irradiation conform to the dose dependence of excess relative risk for myeloid leukemia among atomic bomb survivors in a wide range of doses and in a range of comparatively low doses, respectively. Additionally, the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to continuous irradiation with the dose rate and durations, which were used in brachytherapy, conforms to the dose dependence of excess relative risk for leukemia among the respective groups of exposed patients. These modeling findings demonstrate the potential to use the proposed modeling approach for predicting the excess relative risk for myeloid leukemia among humans exposed to various radiation regimes. Obviously, this is especially important in the assessment of the risks for radiogenic myeloid leukemia among people residing in contaminated areas after an accident or explosion of a radiological device, among astronauts on long-term space missions, as well as among patients treated with radiotherapy.
    Myeloid leukemia risk assessment and dynamics of the granulocytopoietic system in acutely and continuously irradiated humans: modeling approach.
    Health physics, May 2015 [PubMed 25811147]
  • Somatic mitochondrial DNA (mtDNA) mutations have been identified in many human cancers, including leukemia. To identify somatic mutations, it is necessary to have a control tissue from the same individual for comparison. When patients with leukemia achieve remission, the remission peripheral blood may be a suitable and easily accessible control tissue, but this approach has not previously been applied to the study of mtDNA mutations. We have developed and validated a next-generation sequencing approach for the identification of leukemia-associated mtDNA mutations in 26 chronic myeloid leukemia patients at diagnosis using either nonhematopoietic or remission blood samples as the control. The entire mt genome was amplified by long-range PCR and sequenced using Illumina technology. Variant caller software was used to detect mtDNA somatic mutations, and an empirically determined threshold of 2% was applied to minimize false-positive results because of sequencing errors. Mutations were called against both nonhematopoietic and remission controls: the overall concordance between the two approaches was 81% (73/90 mutations). Some discordant results were because of the presence of somatic mutations in remission samples, because of either minimal residual disease or nonleukemic hematopoietic clones. This method could be applied to study somatic mtDNA mutations in leukemia patients who achieve minimal residual disease, and in patients with nonhematopoietic cancers who have a matched uninvolved tissue available.
    A Method for Next-Generation Sequencing of Paired Diagnostic and Remission Samples to Detect Mitochondrial DNA Mutations Associated with Leukemia.
    The Journal of molecular diagnostics : JMD, Jul 2017 [PubMed 28732215]

6. MTTP

2090 articles, score 654.505

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Enriched GO Terms

Abstracts

  • Basophils form a distinct cell lineage within the hematopoietic cell family. In various myeloid neoplasms, including chronic myeloid leukemia, basophilia is frequently seen. Acute and chronic basophilic leukemias, albeit rare, have also been described. However, no generally accepted criteria and classification of basophilic leukemias have been presented to date. To address this unmet need, a series of Working Conferences and other meetings were organized between March 2015 and March 2016. The current article provides a summary of consensus statements from these meetings, together with proposed criteria to delineate acute basophilic leukemia (ABL) from chronic basophilic leukemia (CBL) and primary forms of the disease where no preceding myeloid malignancy is detected, from the more common 'secondary' variants. Moreover, the term hyperbasophilia (HB) is proposed for cases with a persistent peripheral basophil count ⩾1000 per μl of blood. This condition, HB, is highly indicative of the presence of an underlying myeloid neoplasm. Therefore, HB is an important checkpoint in the diagnostic algorithm and requires a detailed hematologic investigation. In these patients, an underlying myeloid malignancy is often found and is then labeled with the appendix -baso, whereas primary cases of ABL or CBL are very rare. The criteria and classification proposed in this article should facilitate the diagnosis and management of patients with unexplained basophilia and basophil neoplasms in routine practice, and in clinical studies.
    Proposed diagnostic criteria and classification of basophilic leukemias and related disorders.
    Leukemia, Apr 2017 [PubMed 28090091]
  • At diagnosis, about 5% of Chronic Myeloid Leukemia (CML) patients lacks Philadelphia chromosome (Ph), despite the presence of the BCR/ABL rearrangement. Two mechanisms have been proposed about the occurrence of this rearrangement: the first one is a cryptic insertion between chromosomes 9 and 22; the second one involves two sequential translocations: a classic t(9;22) followed by a reverse translocation, which reconstitutes the normal morphology of the partner chromosomes. Out of 398 newly diagnosed CML patients, we selected 12 Ph-negative cases. Six Ph-negative patients treated with tyrosine kinase inhibitors (TKIs) were characterized, in order to study the mechanisms leading to the rearrangement and the eventual correlation with prognosis in treatment with TKIs. FISH analysis revealed cryptic insertion in 5 patients and classic translocation in the last one. In more detail, we observed 4 different patterns of rearrangement, suggesting high genetic heterogeneity of these patients. In our cases, the BCR/ABL rearrangement mapped more frequently on 9q34 region than on 22q11 region, in contrast to previous reports. Four patients, with low Sokal risk, achieved Complete Cytogenetic Response and/or Major Molecular Response after TKIs therapy. Therapy resistance was observed in one patient with duplication of BCR/ABL rearrangement and in another one with high risk. Even if the number patient is inevitably low, we can confirm that the rare Ph-negative CML patients do not constitute a "warning" category, meanwhile the presence of further cytogenetic abnormalities remains an adverse prognostic factor even in TKI era.
    Cryptic BCR-ABL fusion gene as variant rearrangement in chronic myeloid leukemia: molecular cytogenetic characterization and influence on TKIs therapy.
    Oncotarget, May 2017 [PubMed 28404889]
  • Clonal myeloid disorders are characterized by genetic alterations that activate cytokine signaling pathways and stimulate cell proliferation. These activated signaling pathways have been extensively studied as potential therapeutic targets, and tyrosine kinase inhibitors have indeed had extraordinary success in treating BCR/ABL-positive chronic myeloiud leukemia. However, although inhibitors of other activated kinases have been developed that perform well in preclinical studies, the therapeutic efficacy of these drugs in patients has been unimpressive. This article discusses potential reasons for these discordant results and outlines recent scientific advances that are informing future efforts to target activated kinases in clonal myeloid disorders.
    Targeting Aberrant Signaling in Myeloid Malignancies: Promise Versus Reality.
    Hematology/oncology clinics of North America, Aug 2017 [PubMed 28673388]

7. ABL1

756 articles, score 427.242

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.
    BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, Jan 2017 [PubMed 28580869]
  • Molecular monitoring of BCR-ABL1 transcript levels using quantitative polymerase chain reaction is an essential part of the modern management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Establishing the diagnostic BCR-ABL1 fusion transcript is necessary in order to select appropriate primers and probes for such monitoring. A case is described in which quantitative polymerase chain reaction failed to detect the presence of BCR-ABL1 fusion transcript in a Philadelphia chromosome-positive chronic myeloid leukemia patient. Further investigation demonstrated a novel in-frame BCR-ABL1 fusion transcript with a breakpoint in BCR exon 13 and insertion of a sequence of ABL1 intron 1, therefore enabling subsequent molecular monitoring. This case highlights the requirement for characterization of the BCR-ABL1 transcript type at chronic myeloid leukemia diagnosis. Issues concerning standardized methodological approaches and interpretation of transcript levels in such rare cases are discussed.
    Characterization of a novel variant BCR-ABL1 fusion transcript in a patient with chronic myeloid leukemia: Implications for molecular monitoring.
    Hematology/oncology and stem cell therapy, Jun 2017 [PubMed 27013275]
  • Chronic myeloid leukemia treatment monitoring using polymerase chain reaction-based peripheral blood testing of t9;22 BCR-ABL1 provides improved test sensitivity over cytology but suffers from inadequate standardization in most laboratories due to variations inherent in the existing polymerase chain reaction methodologies. We performed the initial analytic performance evaluation of a novel competitive template-based peripheral blood b2a2/b3a2 transcript abundance method, called standardized nucleic acid quantification (SNAQ) test, with hypothesis that this will produced more consistent results with less frequent interlaboratory variations. Thirty-six chronic myeloid leukemia patients treated at our institution were enrolled. We compared SNAQ test with 2 laboratory developed test at the MD Anderson molecular diagnostic laboratory and Cancer Genetics Institute for analyzing BCR-ABL1 from peripheral blood samples. Each test result (n=36) was ranked against all the other samples tested by the same method. The Pearson correlation between SNAQ and laboratory developed test done at 2 labs was met by correlations of 0.97, 0.96, 0.96, and 0.94. Analysis of variance of log %BCR-ABL1 interlaboratory results indicated no significant difference (P=0.98). Post hoc analysis of method agreement showed the SNAQ method had a 95% limit of agreement of ±3-fold between laboratories. In this pilot study, SNAQ methodology performed consistent with half-log accuracy. Additional studies from a larger sample size and correlation with clinical outcomes are required to confirm this observation.
    New Tool for Monitoring Molecular Response in Patients With Chronic Myeloid Leukemia.
    Applied immunohistochemistry & molecular morphology : AIMM, Jul 2017 [PubMed 28682832]

8. lymphoblastic leukemia

1297 articles, score 420.299

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • In developing countries, there is commonly a lack of population-based cancer registries or underreporting, thus not recognizing the true dimensions of the problem. To describe the age and sex frequencies of the major subtypes of leukemias in two hospitals of reference in the metropolitan area of Mexico City. This is a descriptive and retrospective study, based on medical records of two hematology services during January 2007 to October 2014; all cases diagnosed with leukemia were included. A total of 1,432 cases were included with a median age of 38 years (range, two months to 115 years). There were significant age differences between subtypes of leukemia (ANOVA test, p = 0.000): chronic lymphocytic with a mean age of 64.8 years, higher than chronic myeloid (43.4 years) and all acute leukemias (lymphoblastic: 32.6 years, myeloblastic 43.5 years). Of the patients, 51.8% (n = 742) were women, although males predominated in chronic myeloid (57.8%) and lymphocytic (60%) leukemia. Acute lymphoblastic leukemia was the more common variety, FABL2 subtype, followed by myeloid leukemia M4, M2, and chronic myeloid. It is necessary to develop inter-institutional works in order to group data of different population sectors and improve the epidemiological profile of leukemia in Mexico.
    [The age and sex frequencies of patients with leukemia seen in two reference centers in the metropolitan area of Mexico City].
    Gaceta medica de Mexico, 2017 [PubMed 28128805]
  • We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality.
    Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, May 2017 [PubMed 28527984]
  • This study was aimed to investigate the effects of myeloid antigen expression on hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia patients post-allogeneic stem cell transplantation (allo-HSCT). Clinical data of 20 patients with acute lymphocytic leukemia in Department of Hematology of the First Affiliated Hospital of Xi'an Jiaotong University from 2008 January to 2014 April were retrospectively analyzed, in which 5 cases were with myeloid antigen (My(+) ALL), while 15 patients were without myeloid antigen expression (My(-) ALL). Differences in prognosis and hematopoietic reconstitution post-allo-HSCT were observed in My(+) ALL and My(-) ALL patients. The results showed that the poor platelet engraftment in patients with My(+) ALL was found more than that in My(-)ALL patients. Three My(+) ALL patients experienced skin chronic graft versus host disease (cGVHD) including local in 2 cases and extensive in one case, and 3 My(-) ALL patients developed grade I-II acute GVHD, while five patients of My(-) ALL experienced cGVHD including local in 3 cases, extensive in 2 cases. One and two year overall survival rate of My(+) ALL and My(-) ALL patients was 80% and 85.7%, 53% and 69.8% respectively, one and two year progress-free survival rate was 53.3% and 54.7%, 26% and 27.4%, respectively. And there was no significant statistical difference between two groups (P > 0.05). It is concluded that the myeloid antigen expression may impact the platelet engraftment post-transplantation. There is no significant difference between one and two year overall survival rate and progress-free survival rate of My(+) ALL and My(-) ALL patients after allogeneic stem cell transplantation.
    [Effects of myeloid antigen expression on hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia patients after allogeneic stem cell transplantation].
    Zhongguo shi yan xue ye xue za zhi, Aug 2014 [PubMed 25130829]

9. myelodysplastic syndromes

957 articles, score 378.571

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • Chronic Myelomonocytic Leukemia is a chronic myeloid neoplasm occurring mostly in the elderly with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) characterized by chronic monocytosis. Recent progresses in the molecular and cellular pathogenesis of CMML have stirred a renewed interest in this clinically heterogeneous disorder. Here, we review the recent progresses in the biology of CMML and how it affects its current and future clinical management.
    CMML: Clinical and molecular aspects.
    International journal of hematology, Jun 2017 [PubMed 28455647]
  • Cytogenetic evolution (CGE) in patients with myeloid neoplasms who relapsed after an allogeneic (allo) hematopoietic cell transplantation (HCT) has been evaluated by only few studies. The effect of the CGE on survival of relapsed allo-HCT recipients is not clear. The effect of previously received chemotherapy to induce CGE in this patient population has not been studied. The aims of our study are to (1) characterize the patterns of cytogenetic change in patients with myeloid neoplasms who relapsed after an allo-HCT, (2) evaluate the effect of CGE on survival, and (3) explore the association of CGE with previous chemotherapy (including the lines of salvage therapy, type of induction, and conditioning therapy). Of 49 patients with a myeloid malignancy (27 acute myeloid leukemia [AML], 19 myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN], and 3 chronic myelogenous leukemia) who relapsed after an allo-HCT, CGE was observed in 25 (51%), whereas 24 patients had unchanged cytogenetic findings at relapse. The CGE group carried more cytogenetic abnormalities at original diagnosis. The most frequent cytogenetic change was the acquisition of 3 or more new chromosomal abnormalities followed by acquisition of unbalanced abnormalities, aneuploidy, and emergence of apparently new clones unrelated to the original clone. The CGE cohort had higher proportion of MDS and MPN and fewer patients with de novo AML. Disease risk assessment category showed a trend to higher frequency of high-risk patients in the CGE group, though the difference was not statistically significant. Time from diagnosis to transplantation and time from transplantation to relapse were not different between the CGE and non-CGE groups. CGE and non-CGE cohorts had similar exposures to salvage therapy and to induction chemotherapy, as well as similar conditioning regimens; thus, no particular type of chemotherapy emerged as a predisposing factor to CGE. CGE was associated with significantly shortened post-transplantation and postrelapse survival when compared with those of the non-CGE group (P = .004 and P < .001, respectively). Our results underscore the significance of CGE in progression of myeloid malignancies after an allo-HCT.
    Cytogenetic Evolution in Myeloid Neoplasms at Relapse after Allogeneic Hematopoietic Cell Transplantation: Association with Previous Chemotherapy and Effect on Survival.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, May 2017 [PubMed 28189903]
  • Patients with acute myeloid leukemia (AML) who relapse after hematopoietic stem cell transplantation (HCT) have dismal outcomes. Our ability to predict those at risk for relapse is limited. We examined chimerism trends post-HCT in 63 children who underwent HCT for AML or myelodysplastic syndrome (MDS). Mixed T-cell chimerism at engraftment and absence of chronic graft versus host disease (cGVHD) were associated with relapse (P = 0.04 and P = 0.02, respectively). Mixed T-cell chimerism at engraftment was predictive in patients without cGVHD (P = 0.03). Patients with engraftment mixed T-cell chimerism may warrant closer disease monitoring and consideration for early intervention.
    Early mixed T-cell chimerism is predictive of pediatric AML or MDS relapse after hematopoietic stem cell transplant.
    Pediatric blood & cancer, Sep 2017 [PubMed 28266766]

10. dasatinib

709 articles, score 328.488

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • kinase domain mutations should always be taken into consideration, among other things. This review mainly focuses on patient selection prior to dasatinib administration in the treatment of chronic myeloid leukemia.
    Dasatinib for the treatment of chronic myeloid leukemia: patient selection and special considerations.
    Drug design, development and therapy, 2016 [PubMed 27784993]
  • Dasatinib is a novel oral prescription drug proposed for treating adult patients with chronic myeloid leukemia. Three analytical methods, namely ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis, were developed, validated, and compared for determination of the drug in the tablet dosage form. The total analysis time of optimized ultra high performance liquid chromatography and capillary zone electrophoresis methods was 2.0 and 2.2 min, respectively. Direct ultraviolet detection with detection wavelength of 322 nm was employed in both cases. The optimized sequential injection analysis method was based on spectrophotometric detection of dasatinib after a simple colorimetric reaction with folin ciocalteau reagent forming a blue-colored complex with an absorbance maximum at 745 nm. The total analysis time was 2.5 min. The ultra high performance liquid chromatography method provided the lowest detection and quantitation limits and the most precise and accurate results. All three newly developed methods were demonstrated to be specific, linear, sensitive, precise, and accurate, providing results satisfactorily meeting the requirements of the pharmaceutical industry, and can be employed for the routine determination of the active pharmaceutical ingredient in the tablet dosage form.
    Determination of dasatinib in the tablet dosage form by ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis.
    Journal of separation science, Jan 2017 [PubMed 27805766]
  • A positive fecal occult blood test (FOBT) is occasionally observed in some chronic myeloid leukemia (CML) patients treated with a tyrosine kinase inhibitor (TKI), and hemorrhagic colitis in patients treated with dasatinib has been reported. To clarify the frequency of TKI-induced hemorrhagic colitis and the screening efficacy of an FOBT followed by a colonoscopy, we prospectively enrolled CML patients treated with a TKI. FOBTs were performed in all patients and colonoscopy was performed in patients with positive FOBTs. When TKI-induced hemorrhagic colitis was pathologically identified, the TKI was interrupted, and the FOBTs were reevaluated. The first FOBT was positive in 10 of 30 patients. All patients with positive FOBTs were treated with dasatinib and developed no symptoms. Dasatinib-induced hemorrhagic colitis was confirmed in 6 of 18 patients treated with dasatinib (33%). Its endoscopic feature was a red flare and/or erosion. Immunohistological analyses showed CD3+, CD8+, CD56+, and Granzyme B+ cytotoxic T lymphocyte infiltration. After dasatinib discontinuation, the FOBTs became negative in all but one patient who had concurrent colorectal polyps. Dasatinib-induced hemorrhagic colitis was observed in one third of asymptomatic patients treated with dasatinib. An FOBT followed by a colonoscopy can be a useful strategy to detect the disease.
    Clinical efficacy of fecal occult blood test and colonoscopy for dasatinib-induced hemorrhagic colitis in CML patients.
    Blood, Nov 2016 [PubMed 27864292]


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