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Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukaemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukaemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukaemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukaemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukaemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36599752
DOI: 10.1016/j.farma.2022.11.002 -
JAMA Network Open Jul 2021Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are... (Meta-Analysis)
Meta-Analysis
Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.
IMPORTANCE
Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity.
OBJECTIVE
To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit.
DATA SOURCES
PubMed, Embase, Cochrane library databases, and ClinicalTrials.gov were searched for clinical trials published between January 2000 and April 2020.
STUDY SELECTION
Study selection was conducted independently by 2 investigators according to the inclusion and exclusion criteria published previously in the protocol: only randomized phase 2 or phase 3 clinical trials that compared bosutinib, dasatinib, nilotinib, or ponatinib with imatinib were included. Among the 2666 records identified, 9 studies finally fulfilled the established criteria.
DATA EXTRACTION AND SYNTHESIS
Two investigators extracted study characteristics and data independently using a standardized data extraction form. Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. When substantial heterogeneity was observed, pooled estimates were calculated based on the random-effect model; otherwise, the fixed-effect model was used.
MAIN OUTCOMES AND MEASURES
Data extracted included study characteristics, baseline patient information, interventions and data on all-grade and high-grade (grades 3 and 4) elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, overall survival, and major molecular response (MMR). The RRs and 95% CIs were calculated using the inverse variance method.
RESULTS
Nine trials involving 3475 patients were analyzed; the median (range) age was 49 (18-91) years; 2059 (59.2%) were male patients. Increased risks were observed for each new-generation TKI except for dasatinib. Patients receiving new-generation TKIs were more likely to experience all grades of ALT elevation (pooled RR, 2.89; 95% CI, 1.78-4.69; P < .001) and grades 3 and 4 ALT elevation (pooled RR, 4.36; 95% CI, 2.00-9.50; P < .001) compared with those receiving imatinib. Patients receiving new-generation TKIs were also more likely to experience all grades of AST elevation (pooled RR, 2.20; 95% CI, 1.63-2.98; P < .001) and grades 3 and 4 AST elevation (pooled RR, 2.65; 95% CI, 1.59-4.42; P < .001) compared with those receiving imatinib. New-generation TKIs were associated with a significantly higher rate of MMR at 1 year compared with imatinib (pooled RR, 1.59; 95% CI, 1.44-1.75; P < .001). No statistical difference in overall survival at 1 year was found between new-generation TKIs and imatinib (pooled RR, 1.00; 95% CI, 1.00-1.01; P = .33).
CONCLUSIONS AND RELEVANCE
When compared to imatinib, bosutinib, nilotinib, and ponatinib had higher relative risks of hepatotoxicity. Treatment with new-generation TKIs was associated with a higher MMR rate at 1 year but not with 1-year overall survival.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Aniline Compounds; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Dasatinib; Female; Humans; Imatinib Mesylate; Imidazoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Nitriles; Oncogene Proteins v-abl; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-bcr; Pyridazines; Pyrimidines; Quinolines; Risk; Young Adult
PubMed: 34292334
DOI: 10.1001/jamanetworkopen.2021.20165 -
Acta Bio-medica : Atenei Parmensis Jan 2022Philadelphia negative myeloproliferative neoplasms (MPNs) are classically characterized by excess production of terminal myeloid cells in the peripheral blood. They...
Philadelphia negative myeloproliferative neoplasms (MPNs) are classically characterized by excess production of terminal myeloid cells in the peripheral blood. They include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Among this group, primary myelofibrosis is the least common and usually carries the worst prognosis. Bone involvement in primary myelofibrosis has many forms; it affects bone marrow leading to bone marrow fibrosis, it can cause periostitis, in addition to bone and joint pain. A common radiologic finding in primary myelofibrosis is the presence of osteosclerotic lesions. However, the presence of osteolytic lesions in bone imaging was described in few reports. In this review, we searched English literature using the PRISMA guidelines looking for patients with Primary myelofibrosis who had osteolytic bone lesions to assess the impact of such findings on the disease and its effect on prognosis. We found the vast majority of lesions were painful affecting most commonly the vertebral column, pelvis, and ribs, and were detected in patients above 50 years of age with no gender preference, unfortunately they represented advanced disease stages, resulting in inadequate treatment response and poor outcome.
Topics: Bone Marrow; Humans; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 35075062
DOI: 10.23750/abm.v92i6.12350 -
The Oncologist Aug 2022This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem...
BACKGROUND
This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem cell transplantation (HSCT), although the small number of patients has limited study of their efficacy. Herein, we present all available cases in the current searchable literature with their demographics, diagnoses, treatments, and outcomes.
METHODS
PubMed, ScienceDirect, Publons, the Cochrane Library, and Google were searched with the following terms: PCM1-JAK2, ruxolitinib and myeloid/lymphoid.
RESULTS
Sixty-six patients (mean age = 50, 77% male) had an initial diagnosis of myeloproliferative neoplasm (MPN) in 40, acute leukemia in 21 and T-cell cutaneous lymphoma in 5. Thirty-five patients (53%) had completed 5-year follow-up. The 5-year survival for the MPN, acute myelogenous leukemia (AML), acute lymphocytic leukemia, and lymphoma groups are 62.7, 14.9%, 40.0%, and 100%, respectively. Too few patients have been treated with ruxolitinib to draw conclusions regarding its effect on survival while the 5-year survival for MPN patients with or without HSCT was 80.2% (40.3%-94.8%) versus 51.5% (22.3%-74.6%), respectively. The T-cell cutaneous lymphoma patients have all survived at least 7 years.
CONCLUSION
This rare condition may be increasingly detected with wider use of genomics. Ruxolitinib can yield hematologic and molecular remissions. However, HSCT is, at this time, the only potentially curative treatment. Useful prognostic markers are needed to determine appropriate timing for HSCT in patients with MPN. Patients presenting with acute leukemia have a poor prognosis.
Topics: Female; Humans; Janus Kinase 2; Leukemia; Lymphoma; Male; Middle Aged; Myeloproliferative Disorders; Oncogene Proteins, Fusion
PubMed: 35472244
DOI: 10.1093/oncolo/oyac072 -
Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Antineoplastic Agents; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36870818
DOI: 10.1016/j.farma.2023.02.002 -
Cytometry. Part B, Clinical Cytometry May 2021
Topics: Aged, 80 and over; CD4 Antigens; CD56 Antigen; Dendritic Cells; Flow Cytometry; Humans; Leukemia, Myelomonocytic, Chronic; Male; Myeloproliferative Disorders; Skin Neoplasms
PubMed: 32830878
DOI: 10.1002/cyto.b.21932 -
Acta Bio-medica : Atenei Parmensis Mar 2022Objective: Avascular necrosis (AVN)has been encountered in hematological malignancies; nonetheless, AVN is extremely uncommon in patients with chronic myeloid leukemia...
UNLABELLED
Objective: Avascular necrosis (AVN)has been encountered in hematological malignancies; nonetheless, AVN is extremely uncommon in patients with chronic myeloid leukemia (CML). This review aims to describe the pathophysiology, clinical characteristics, and outcomes of AVN in CML. To our knowledge, this is the first systematic review of this topic.
METHODS
We searched PubMed and Google Scholar for the case reports and series of patients with CML who developed AVN from inception to July 2021.
RESULTS
We found 21 cases of AVN in CML patients,17 cases with avascular necrosis of the femoral head (AVNFH), and four cases with osteonecrosis of the jaw (ONJ). The median age was 39 years with an almost equal distribution between males and females (ratio of 1:1). AVN related to CML management has been linked to tyrosine kinase inhibitors (TKIs) and standard interferon-alpha (IFN-α) therapies. Only six (out of 17) patients who developed AVN of the femoral head eventually required a hip replacement, and one (out of 17) developed a recurrent episode of AVNFH. All the reported cases of CML with osteonecrosis of the jaw were associated with TKIs therapy.
CONCLUSION
Clinician should consider AVN in any CML patient complaining of either hip or jaw pain. IFN-α and TKI therapies can predispose to AVN in CML patients. Further studies are required for a better understanding of this condition in CML.
Topics: Adult; Arthroplasty, Replacement, Hip; Female; Femur Head Necrosis; Humans; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male
PubMed: 35315390
DOI: 10.23750/abm.v93i1.12270 -
American Journal of Clinical Oncology Jun 2021Lack of adherence to tyrosine kinase inhibitors (TKIs) is a significant problem resulting in incomplete cytogenetic response and increased mortality in patients with...
BACKGROUND
Lack of adherence to tyrosine kinase inhibitors (TKIs) is a significant problem resulting in incomplete cytogenetic response and increased mortality in patients with chronic myeloid leukemia (CML). Few studies have been conducted on interventions to improve adherence. The authors conducted a systematic review to explore studies that examined the impact of strategies to improve TKI adherence among individuals with CML.
METHODS
The first 2 authors completed a systematic literature review according to the guidelines in Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Studies (n=2633) conducted between 1980 and 2019 were identified through 3 databases and examined for inclusion/exclusion criteria.
RESULTS
Fourteen studies were identified which met the eligibility criteria. The studies only examined adherence to imatinib, dasatinib, or nilotinib. Ten of the 14 used large data sets (commercial health insurance plans or Surveillance Epidemiology and End Results [SEER] data) for analysis. The majority of the studies used a cohort design. Adherence was defined and measured in a variety of ways with most studies using 80% or higher as adequate adherence. Strategies not focused on health care costs used a multidisciplinary team approach.
CONCLUSION
Development of evidence to improve treatment adherence to TKIs for CML have relied on large data sets rather than prospective trials. Current studies lack patient focused interventions.
Topics: Health Care Costs; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Medication Adherence; Prognosis; Protein Kinase Inhibitors
PubMed: 33867480
DOI: 10.1097/COC.0000000000000818 -
Blood Advances Jan 2020Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea;... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea; however, evidence regarding its efficacy in terms of thrombosis reduction is uncertain. We searched Medline, Embase, and archives of abstracts from the European Hematology Association and the American Society of Hematology annual congresses from 2014 onward for randomized controlled trials comparing the treatment vs best available therapy (BAT). Our search retrieved 80 records; after screening of abstracts and full text, the total was reduced to 16. Evidence came from 4 randomized controlled trials, including 663 patients (1057 patients per year). We estimated a thrombosis risk ratio of 0.56 for ruxolitinib BAT, corresponding to an incidence of 3.09% and 5.51% patients per year, respectively. The number of thrombotic events reported with ruxolitinib was consistently lower than that with BAT in our sample, but, globally, the difference did not reach significance (P = .098). Hard evidence in favor of ruxolitinib is lacking; a clinical trial on selected patients at high risk of thrombosis would be warranted, but its feasibility is questionable.
Topics: Humans; Nitriles; Odds Ratio; Polycythemia Vera; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Thrombosis; Treatment Outcome
PubMed: 31985808
DOI: 10.1182/bloodadvances.2019001158 -
Medical Oncology (Northwood, London,... Apr 2024Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell... (Review)
Review
Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell (HSC) self-renewal and the generation of specialized cells. Cytokines and chemokines, two important components of the inflammatory process, also influence hematological differentiation. In this scenario, immunological dysregulation plays a pivotal role in the pathogenesis of bone marrow neoplasms. The STING pathway recognizes DNA fragments in the cell cytoplasm and triggers an immune response by type I interferons. The role of STING in cancer has not yet been established; however, both actions, as an oncogene or tumor suppressor, have been documented in other types of cancer. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42023407512) to discuss the role of STING pathway in the advancement of pathogenesis and/or prognosis for different myeloid neoplasms. In brief, scientific evidence supports investigations that primarily use cell lines from myeloid neoplasms, such as leukemia. More high-quality research and clinical trials are needed to understand the role of the STING pathway in the pathology of hematological malignancies. Finally, the STING pathway suggests being a promising therapeutic molecular target, particularly when combined with current drug therapies.
Topics: Humans; Hematologic Neoplasms; Membrane Proteins; Myeloproliferative Disorders; Signal Transduction
PubMed: 38656461
DOI: 10.1007/s12032-024-02376-8