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Pathobiology : Journal of... 2023Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic...
INTRODUCTION
Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic disorders or consequent to bone marrow transplant. Its molecular characterization has become an increasingly important requirement for the diagnostic definition of this solid leukemia.
CASE PRESENTATION
Our case report concerns an MS arising in the breast of a woman with a previous diagnosis of JAK2-mutated essential thrombocythemia (Val617Phe exon 14p) mimicking, on histology, a lobular carcinoma of the breast. The immunohistochemical study of the neoplasm provided the key that solved the diagnostic doubt and the immunohistochemical evaluation of NPM protein expression, which turn out to be negative, provided a clear indication on the molecular status and prognosis of the disease. A year later, the neoplasm relapsed in the pelvic area.
DISCUSSION
This diagnostic challenge led us to review the literature of the past 10 years concerning MS of the breast. To the best of our knowledge, this was the first case of MS of the breast occurring in a patient with a history of essential thrombocythemia and recurred in the pelvic region.
Topics: Female; Humans; Thrombocythemia, Essential; Sarcoma, Myeloid; Blast Crisis; Leukemia; Exons; Janus Kinase 2
PubMed: 35850113
DOI: 10.1159/000525163 -
Expert Review of Hematology May 2022Chronic myeloid leukemia at myeloid blastic phase (CML-MBP) is a rapidly lethal illness, and its prognosis is dismal with standard therapy. As the clinical and...
INTRODUCTION
Chronic myeloid leukemia at myeloid blastic phase (CML-MBP) is a rapidly lethal illness, and its prognosis is dismal with standard therapy. As the clinical and histological characteristics of CML-MBP closely resemble acute myeloid leukemia (AML), the management of these two entities has historically gone hand in hand. The remarkable success of tyrosine kinase inhibitors (TKI) for chronic phase CML significantly reduced the incidence of CML-MBP.
AREA COVERED
We performed a systematic literature review to aggregate the clinical data of CML-MBP patients who have been treated with the new drugs approved for use in AML, including decitabine, azacytidine, venetoclax, omecetaxine, glasdegib, gemtuzumab, , and inhibitors. The literature review revealed 14 articles directly contributing relevant data. We analyzed them according to the type of regimen each studied. This review will highlight selected findings from these papers.
EXPERT OPINION
Hypomethylating agent and TKI combination with or without the addition of venetoclax appear to be highly promising and have produced comparable outcomes with intensive chemotherapy and TKI combinations. Current evidence is insufficient to reach conclusions prompting dedicated research to improve the care of patients with CML-MBP.
Topics: Azacitidine; Gemtuzumab; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Protein Kinase Inhibitors
PubMed: 35536916
DOI: 10.1080/17474086.2022.2076669 -
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 -
Journal of Comparative Effectiveness... Jun 2022To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid... (Review)
Review
To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid leukemia (CML). We identified 155 references in Chinese- and English-language journals from 2001 to 2021. The age-adjusted mortality rate in Chinese CML patients was decreasing. Imatinib treatment had a higher annual treatment failure risk than nilotinib (0.199 vs 0.041). Patients with TKI treatment failure tended to be young (median: 38.6 years), have progressive disease (44.3%) and harbor mutations (51.6%). The disease burden of TKI treatment failure included reduced health outcomes and increased health resource utilization and costs. CML relapse cases could continuously rise in China due to increasing TKI treatment failure over extended survival.
Topics: Asian People; Humans; Imatinib Mesylate; Language; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors
PubMed: 35411807
DOI: 10.2217/cer-2022-0032 -
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 -
Journal of Oncology Pharmacy Practice :... Sep 2022To provide up to date guidance, practice recommendations and highlight barriers to medication adherence in the long-term management of chronic myeloproliferative...
PURPOSE
To provide up to date guidance, practice recommendations and highlight barriers to medication adherence in the long-term management of chronic myeloproliferative neoplasms (MPNs).
AIM
Current drug therapy for MPN is not curative and has not been shown to prolong survival. The main indication for treatment is the prevention of thrombosis and medication adherence remains a challenge in this group of patients. Identifying potentially modifiable barriers to medication adherence including primary nonadherence and non-persistent adherence enables timely interventions to be put in place and improve overall medication adherence.
METHODS
A systematic review of peer-reviewed literature and expert opinions was performed using electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) that were searched for articles reporting MPN and medication adherence. Discussions A case vignette is discussed throughout the article and expert opinion with international peer reviewed guidelines that are authored to support clinical decision making at the point of care were utilised. The evidence base was combined with more practical/clinical (data based) insight from real world clinical practice. Adoption of a broad range of digital health care activities and services in the health care system (telehealth applications) by the advanced practice providers (Non-Medical Prescribers-NMPs) in MPN clinics included medication prescribing and management, oral drug compliance and adherence evaluations, interventions, chronic care management, counselling and patient education on treatments.
CONCLUSION
Current drug therapy for MPN is neither curative nor has it been shown to prolong survival, and medication adherence remains a challenge in this group of patients. The longevity of the patients' disease course may contribute to the high risk of non-adherence in this patient cohort. Poor adherence to long-term therapies severely compromises the effectiveness of treatment. Adherence interventions should be tailored to the needs of the patient in order to achieve maximum impact. Interventions aimed at improving adherence provide the best experience and outcome for the patient and their families and can have a profound impact on the quality of life and mitigation of disease consequences.
Topics: Humans; Medication Adherence; Myeloproliferative Disorders; Neoplasms; Quality of Life; Thrombosis
PubMed: 35296179
DOI: 10.1177/10781552221082293 -
European Journal of Haematology Jun 2022Molecular biomarker tests can inform the clinical management of genomic heterogeneous hematological malignancies, yet their availability in routine care largely depends...
OBJECTIVES
Molecular biomarker tests can inform the clinical management of genomic heterogeneous hematological malignancies, yet their availability in routine care largely depends on the supporting health economic evidence. This study aims to systematically review the economic evidence for recent molecular biomarker tests in hematological malignancies.
METHODS
We conducted a systematic search in five electronic databases for studies published between January 2010 and October 2020. Publications were independently screened by two reviewers. Clinical study characteristics, economic methodology, and results were extracted, and reporting quality was assessed.
RESULTS
Fourteen studies were identified, of which half (n = 7; 50%) were full economic evaluations examining both health and economic outcomes. Studies were predominantly conducted in a first-line treatment setting (n = 7; 50%) and adopted a non-lifetime time horizon to measure health outcomes and costs (n = 7; 50%). Five studies reported that companion diagnostics for associated therapies were likely cost-effective for acute myeloid leukemia, chronic myeloid leukemia, diffuse large B-cell lymphoma, and multiple myeloma. Four studies suggested molecular biomarker tests for treatment monitoring in chronic myeloid leukemia were likely cost-saving.
CONCLUSIONS
Although there is initial confirmation of the promising health economic results, the present research for molecular biomarker tests in hematological malignancies is sparse with many applications of technological advances yet to be evaluated.
Topics: Biomarkers; Cost-Benefit Analysis; Hematologic Neoplasms; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
PubMed: 35158410
DOI: 10.1111/ejh.13755 -
Acta Bio-medica : Atenei Parmensis Jan 2022Myasthenia Gravis (MG) is a rare neurological condition characterized by muscle weakness that worsens after use. Myeloproliferative Neoplasms (MPNs) are disorders due to...
Myasthenia Gravis (MG) is a rare neurological condition characterized by muscle weakness that worsens after use. Myeloproliferative Neoplasms (MPNs) are disorders due to stem-cell hyperplasia characterized by an increased peripheral blood cell count, overactive bone marrow, and proliferation of mature hematopoietic cells. MPNs may be Philadelphia (Ph) chromosome-positive or Negative .A systematic review of case reports was conducted by searching PubMed, Scopus, and Google scholar to identify case reports in which there is an association between MG and MPN and know whether MG can be considered a possible neurological paraneoplastic syndrome in patients with MPNs. A total of 13 cases of MPNs associated with MG were identified. The most common type of MPN associated with MG was chronic myeloid leukemia (CML) (10 out of 13 patients). In most of the patients, MG symptoms appeared after a diagnosis of MPN was made. Considering that 10 out of the 13 patients in our cohort had positive auto-antibodies though only 4 of them had thymic hyperplasia, we hypothesize that bone marrow proliferation was responsible for the production of autoantibodies in these patients.As the clonal cell population cannot be eliminated entirely in the bone marrow even after treatment with tyrosine kinase inhibitors (TKI) in Ph +ve MPNs and JAK2 inhibitors in Ph -ve MPNS, MG can occur even in patients who are treated with these agents. A high index of suspicion is needed to diagnose it early, and treatment should be initiated immediately with steroids and anticholinergic agents.
Topics: Bone Marrow; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myasthenia Gravis; Myeloproliferative Disorders; Paraneoplastic Syndromes, Nervous System
PubMed: 35075066
DOI: 10.23750/abm.v92i6.12180 -
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 -
Computational and Mathematical Methods... 2021The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly... (Meta-Analysis)
Meta-Analysis
Second-Generation Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response: A Systematic Review and a Meta-Analysis.
The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly diagnosed chronic phase-chronic myeloid leukemia (CP-CML) patients as compared with imatinab. A number of studies on the discontinuation of 2G-TKIs have been conducted and recently published. A meta-analysis was conducted in this study to assess the rate of treatment-free remission (TFR) rate as well as the long-term safety of 2G-TKI discontinuation in CML patients with stable deep molecular response (DMR). 517 patients were recruited in 5 single-armed, prospective cohort studies. The overall weighted mean TFR rate at the follow-up of 12 months reached 57% (95% CI 51-64%; = 56.4%). The weighted mean TFR rate at the 24-month follow-up was 53% (95% CI 47-60%; = 47.1%). The loss of TFR was primarily concentrated in the first 12 months. 96.5% of patients, having restarted TKI therapy after a molecular relapse, achieved major molecular response (MMR) rapidly. There were four deaths at the two-year follow-up. As suggested from the results of the final study, 2G-TKI discontinuation in CML patients with stable DMR was reported to be feasible. Relapsed patients were retreated with 2G-TKI, and over 95% of patients could reach MMR. Almost no deaths occurred due to adverse events in two years after discontinuation, and more than half of the patients could maintain a TFR.
Topics: Antineoplastic Agents; Computational Biology; Dasatinib; Disease-Free Survival; Duration of Therapy; Female; Humans; Imatinib Mesylate; Leukemia, Myeloid, Chronic-Phase; Male; Protein Kinase Inhibitors; Pyrimidines; Recurrence; Remission Induction
PubMed: 34956393
DOI: 10.1155/2021/3110622