Hits 1 - 10 (out of 6088 matching entities) [11557 mentions] (34 ms):
1. chronic myeloid leukemias

9534 articles, score 4465.527

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Molecular Interaction Network

Enriched GO Terms

Abstracts

  • Many diseases have their treatment options narrowed and end up being fatal if detected during later stages. As a consequence, point-of-care devices have an increasing importance for routine screening applications in the health sector due to their portability, fast analyses and decreased cost. For that purpose, a multifunctional chip was developed and tested using gold nanoprobes to perform RNA optical detection inside a microfluidic chip without the need of molecular amplification steps. As a proof-of-concept, this device was used for the rapid detection of chronic myeloid leukemia, a hemato-oncological disease that would benefit from early stage diagnostics and screening tests. The chip passively mixed target RNA from samples, gold nanoprobes and saline solution to infer a result from their final colorimetric properties. An optical fiber network was used to evaluate its transmitted spectra inside the chip. Trials provided accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB. When compared to actual state-of-art screening techniques of chronic myeloid leukemia, these results were, at microscale, at least 10 times faster than the reported detection methods for chronic myeloid leukemia. Concerning point-of-care applications, this work paves the way for other new and more complex versions of optical based genosensors.
    Multifunctional microfluidic chip for optical nanoprobe based RNA detection - application to Chronic Myeloid Leukemia.
    Scientific reports, Jan 2018 [PubMed 29321602]
  • Medication non-adherence is associated with poor health outcomes and increased health care costs. Depending on definitions, reported non-adherence rates in cancer patients ranges between 16 and 100%, which illustrates a serious problem. In malignancy, non-adherence reduces chances of achievement of treatment response and may thereby lead to progression or even relapse. Except for Chronic Myeloid Leukemia (CML), the extent of non-adherence has not been investigated in hematological-oncological patients in an outpatient setting. In order to explore ways to optimize cancer treatment results, this study aimed to assess the prevalence of self-administered medication non-adherence and to identify potential associated factors in hematological-oncological patients in their home situation. This is an exploratory cross-sectional study, carried out at the outpatient clinic of the Department of Hematology at the VU University medical center, Amsterdam, the Netherlands between February and April 2014. Hematological-oncological outpatients were sent questionnaires retrieving information on patient characteristics, medication adherence, beliefs about medication, anxiety, depression, coping, and quality of life. We performed uni- and multivariable analysis to identify predictors for medication non-adherence. In total, 472 participants were approached of which 259 (55%) completed the questionnaire and met eligibility criteria. Prevalence of adherence in this group (140 male; 54,1%; median age 60 (18-91)) was 50%. In univariate analysis, (lower) age, (higher) education level, living alone, working, perception of receiving insufficient social support, use of bisphosphonates, depression, helplessness (ICQ), global health, role function, emotional function, cognitive function, social functioning, fatigue, dyspnea, diarrhea were found to be significantly related (p = <0.20) to medication non-adherence. In multivariable analysis, younger age, (higher) education level and fatigue remained significantly related (p = <0.10) to medication non-adherence. This cross-sectional study shows that 50% of the participants were non-adherent. Lower age, living alone and perception of insufficient social support were associated factors of non-adherence in hematological-oncological adult patients in their home-situation.
    Prevalence and associated factors of medication non-adherence in hematological-oncological patients in their home situation.
    BMC cancer, Nov 2017 [PubMed 29121889]
  • We investigated factors that physicians consider of most importance in the selection of second line tyrosine kinase inhibitors treatments (TKIs) in chronic myeloid leukemia patients (CML).
    Physicians' attitude towards selection of second line therapy with nilotinib and dasatinib in chronic myeloid leukemia patients.
    Health and quality of life outcomes, Oct 2017 [PubMed 29047379]

2. imatinib

3141 articles, score 1338.861

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Enriched GO Terms

Abstracts

  • ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p < 0.0001). Moreover, +68GA del/del and ins/del genotypes in imatinib-treated chronic myeloid leukemia patients were associated with an increased risk of developing thrombocytopenia, with odds ratios 6.5 (95% confidence interval = 2.02-0.89, p = 0.001) and 6.0 (95% confidence interval = 2.26-15.91, p = 0.0002), respectively. Similarly, -909C/A promoter polymorphism genotype distribution also differed significantly between thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p = 0.02), and a significantly increased risk of imatinib-induced thrombocytopenia was associated with -909C/A polymorphism mutant homozygous (AA) genotypes the odds ratio being 7.7 (95% confidence interval 1.50 to 39.91, p = 0.009). However, no significant risk of imatinib-induced thrombocytopenia was found to be associated with heterozygous genotype (-909C/A) with odds ratio 1.9 (95% confidence interval = 0.86-4.56, p = 1.14). Platelet-derived growth factor receptor-α messenger RNA expression was significantly higher in chronic myeloid leukemia patients compared to controls (p = 0.008). Moreover, patients with imatinib-induced thrombocytopenia had a significantly lower platelet-derived growth factor receptor-α messenger RNA expression, compared to patients without thrombocytopenia (p = 0.01). A differential expression of platelet-derived growth factor receptor-α messenger RNA was observed with respect to different +68 GA ins/del and -909C/A polymorphism genotypes. The +68GA deletion allele and -909A allele were significantly associated with lower expression of platelet-derived growth factor receptor-α messenger RNA. The platelet-derived growth factor receptor-α +68GA del/del, +68GA ins/del, and -909AA genotypes are associated with an increased risk of developing thrombocytopenia in imatinib-treated chronic myeloid leukemia patients. A significantly lower platelet-derived growth factor receptor-α messenger RNA expression accompanies the +68GA deletion allele in an allele dose-dependent manner. Platelet-derived growth factor receptor-α -909AA genotype is also associated with lower expression of platelet-derived growth factor receptor-α. The downregulation of platelet-derived growth factor receptor-α expression may play a causative role in imatinib-induced thrombocytopenia, a common side effect, in the subset of chronic myeloid leukemia patients with platelet-derived growth factor receptor-α +68 GA ins/del, +68 GA del/del, and -909C/A genotypes.
    PDGFRα promoter polymorphisms and expression patterns influence risk of development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A study from India.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Oct 2017 [PubMed 29019285]
  • Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR. The imatinib sensitive CML cells transfected with pre-miR-365 displayed lower chemosensitivity and apoptosis rate compared with controls. We further confirmed that exosomal transfer of miR-365 induced drug resistance by inhibiting expression of pro-apoptosis protein in sensitive CML cells. In conclusion, our study reveals that exosomes mediate a horizontal transfer of drug-resistant trait in chronic myeloid leukemia cell by delivering miR-365.
    Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365.
    Experimental cell research, Jan 2018 [PubMed 29223442]
  • Generic imatinib therapy is being globally considered owing to cost considerations. However, evidence of its efficacy and safety in Middle Eastern clinical settings is scarce. The efficacy and safety of generic imatinib (Cemivil) were assessed among Jordanian patients diagnosed with chronic myeloid leukemia using an observational, multicenter, prospective study design. Responses were defined using European LeukemiaNet 2009 guidelines and assessed by complete blood counts, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. All patients (N = 91) were adults with chronic myeloid leukemia treated with generic imatinib 400 mg/day. Thirty-three patients received generic imatinib as first-line therapy, and 58 switched from patented imatinib to generic imatinib after a median of 4.5 years (range, 0.5-13.6 years) of imatinib therapy. The majority (85%; n = 28) of the first-line patients achieved complete hematologic response within 3 months of starting generic imatinib therapy (100% after 6 months [n = 33]). The 12-month major molecular response rate in the intention-to-treat population was 45%. The 12-month major molecular response rate was 88% for patients who switched therapy. The 12-month progression-free and overall survival rates were 92% and 100%, respectively. Most (85%; n = 144) adverse events were mild. Frequencies of drug-related adverse events were similar to patented imatinib. This study suggests that the efficacy and safety of generic imatinib in this Middle Eastern population in routine clinical practice are comparable to patented imatinib, and to that of the global population.
    Generic Imatinib Therapy Among Jordanians: An Observational Assessment of Efficacy and Safety in Routine Clinical Practice.
    Clinical lymphoma, myeloma & leukemia, Dec 2017 [PubMed 28844599]

3. acute myeloid leukemias

2691 articles, score 1122.006

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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]
  • Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. Case Series and review of the literature. We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient. Although a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft-versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement.
    Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant.
    Journal of pediatric hematology/oncology, Nov 2017 [PubMed 28991134]
  • 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]

4. leukemias

2673 articles, score 1060.368

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Enriched GO Terms

Abstracts

  • The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.
    Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT.
    Journal of internal medicine, Feb 2018 [PubMed 28977716]
  • 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]
  • Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. Case Series and review of the literature. We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient. Although a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft-versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement.
    Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant.
    Journal of pediatric hematology/oncology, Nov 2017 [PubMed 28991134]

5. BCR

2749 articles, score 1019.643

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]
  • Imatinib was the first tyrosine kinase inhibitor that has revolutionized the therapy of chronic myeloid leukemia. It binds breakpoint cluster region-Abelson kinase domain inducing apoptosis of the leukemic cells. In this study, we assessed the efficacy and toxicity of imatinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) in our hospital. We retrospectively analyzed the outcome of 17 patients with CML-CP treated with imatinib. The median age at the time of presentation was 35 years with male preponderance. The most common presenting clinical features were fatigue, abdominal distention, and discomfort. Forty-seven percent of patients had fever at presentation whereas 35.29% were referred to our hospital because of incidental findings of high blood cell counts. With a median follow-up of 8 years (range, 2-16 years) the overall survival is 100% and progression-free survival 85%. Two patients had acceptable adverse effects. After a median follow-up of 8 years, imatinib was found to induce long survival with manageable side effect in adult Saudi patients with CML-CP.
    Outcome of Chronic Myeloid Leukemia-Chronic Phase Patients Treated With Imatinib: A Local Experience.
    Clinical lymphoma, myeloma & leukemia, Jan 2018 [PubMed 29397347]
  • 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]

6. MTTP

2143 articles, score 642.602

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Enriched GO Terms

Abstracts

  • findings using a functional pre-clinical mouse model of chronic myeloid leukemia (CML), whereby we demonstrated the ability of NOX-A12, combined with the ABL kinase inhibitor, nilotinib, to reduce the leukemia burden in mice to a greater extent than either agent alone. Overall, the data support the idea of using SDF-1 inhibition in combination with targeted kinase inhibition to override drug resistance in oncogene-driven leukemia to significantly diminish or eradicate residual leukemic disease.
    Inhibition of SDF-1-induced migration of oncogene-driven myeloid leukemia by the L-RNA aptamer (Spiegelmer), NOX-A12, and potentiation of tyrosine kinase inhibition.
    Oncotarget, Dec 2017 [PubMed 29299123]
  • 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]

7. ABL1

801 articles, score 438.364

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]
  • Nowadays, more than 90% of patients affected by chronic myeloid leukemia (CML) survive with a good quality of life, thanks to the clinical efficacy of tyrosine kinase inhibitors (TKIs). Nevertheless, point mutations of the ABL1 pocket occurring during treatment may reduce binding of TKIs, being responsible of about 20% of cases of resistance among CML patients. In addition, the presence of leukemic stem cells (LSCs) represents the most important event in leukemia progression related to TKI resistance. LSCs express stem cell markers, including active efflux pumps and genetic and epigenetic alterations together with deregulated cell signaling pathways involved in self-renewal, such as Wnt/β-catenin, Notch, and Hedgehog. Moreover, the interaction with the bone marrow microenvironment, also known as hematopoietic niche, may influence the phenotype of surrounding cells, which evade mechanisms controlling cell proliferation and are less sensitive or frankly resistant to TKIs. This Review focuses on the role of LSCs and stem cell niche in relation to response to pharmacological treatments. A literature search from PubMed database was performed until April 30, 2017, and it has been analyzed according to keywords such as chronic myeloid leukemia, stem cell, leukemic stem cells, hematopoietic niche, tyrosine kinase inhibitors, and drug resistance. Stem Cells Translational Medicine 2018.
    Concise Review: Chronic Myeloid Leukemia: Stem Cell Niche and Response to Pharmacologic Treatment.
    Stem cells translational medicine, Feb 2018 [PubMed 29418079]

8. lymphoblastic leukemia

1329 articles, score 430.917

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, Sep 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

984 articles, score 379.898

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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

756 articles, score 346.138

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Enriched GO Terms

Abstracts

  • Chronic myeloid leukemia (CML) has evolved into a chronic disease that is managed with tyrosine kinase inhibitor therapy. Now that long-term survival has been achieved in patients with CML, the focus of treatment has shifted to dose optimization, with the goal of maintaining response while improving quality of life. In this review, the authors discuss optimizing the dose of the second-generation tyrosine kinase inhibitor dasatinib. Once-daily dosing regimens for dasatinib in the first and later lines of treatment were established through long-term (5-year and 7-year) trials. Recently published data have indicated that further dose optimization may maintain efficacy while minimizing adverse events. Results obtained from dose optimization and discontinuation trials currently in progress will help practitioners determine the best dose and duration of dasatinib for patients with CML, because treatment decisions will be made through continued discussions between physicians and patients. Cancer 2018. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
    Dasatinib dose management for the treatment of chronic myeloid leukemia.
    Cancer, Jan 2018 [PubMed 29370463]
  • Pregnancy in a patient with chronic myeloid leukemia presents a therapeutic challenge. Both dasatinib and nilotinib are indicated for first-line treatment as well as for treatment-resistant chronic myeloid leukemia. Animal studies with dasatinib or nilotinib demonstrate fetal skeletal malformations as well as significant mortality during organogenesis. The goal of this article is to review the experience to date of dasatinib and nilotinib in human pregnancy, specifically dasatinib and nilotinib dose, length of exposure, trimester of use, as well as patient and fetal outcomes. Based on the limited data, both dasatinib and nilotinib may cause fetal harm. Additionally, thorough analysis of the available literature indicates no correlation between dasatinib nor nilotinib dose, length of exposure, trimester of use, and deleterious patient or fetal outcomes can be concluded. Therefore, health care professionals need to regularly counsel women of child bearing potential with chronic myeloid leukemia regarding the risks of taking dasatinib or nilotinib during pregnancy. The safest potential therapeutic options for the management of chronic myeloid leukemia in pregnancy include temporary discontinuation of the tyrosine kinase inhibitor followed by observation or intervention with interferon alfa and/or leukapheresis.
    Experience with dasatinib and nilotinib use in pregnancy.
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, Mar 2018 [PubMed 29284357]
  • Preclinical animal studies have demonstrated an association between maternal use of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical case series have reported normal pregnancy outcomes and healthy infants in women on these medications during the course of their pregnancy. We describe a case of a woman with chronic myeloid leukemia who had taken the second-generation tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic diamniotic twin pregnancy and subsequently delivered two low-birth weight infants, one with severe cardiac malformations and the other without apparent birth abnormalities. To our knowledge, this is the first reported case of fetal cardiovascular defects in an infant born to a woman on dasatinib during a twin pregnancy and supports current recommendations to avoid this medication during pregnancy. We also review relevant preclinical and clinical studies of tyrosine kinase inhibitor use during pregnancy and explore alternative therapeutic options for patients with chronic myeloid leukemia during pregnancy to aid clinicians in the appropriate management of these patients so as to minimize both maternal and fetal risks.
    Cardiac birth defects in a twin infant born to a woman with chronic myeloid leukemia on dasatinib.
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, Jan 2017 [PubMed 29207935]


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