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The Tohoku Journal of Experimental... Jun 2021Myeloid sarcoma is a rare disease entity of extramedullary myeloid neoplasm that can occur both as an initial isolated myeloid sarcoma without leukemic cell invasion in...
Myeloid sarcoma is a rare disease entity of extramedullary myeloid neoplasm that can occur both as an initial isolated myeloid sarcoma without leukemic cell invasion in the peripheral blood and bone marrow, and as the secondary lesion of acute and chronic myeloid leukemias, myelodysplastic syndrome and chronic myeloproliferative neoplasms. Due to its rarity and its frequent emergence as the recurrent lesion after intensive systemic therapy, including allogeneic hematopoietic stem cell transplantation, the standard treatment has not been established for myeloid sarcoma. In this report, we presented an 84-year-old female patient with isolated myeloid sarcoma which progressed to myelodysplastic syndrome and systemic myeloid sarcoma despite various types of conventional anti-leukemic chemotherapies. However, the patient got a durable partial response by the monotherapy of azacitidine, a hypomethylating agent. She received thirteen courses of azacitidine therapy without progression. We discuss the possibility that hypomethylating agents are the novel effective and feasible therapeutic options for myeloid sarcoma, even in cases refractory to or relapsed after intensive systemic treatment. We also discuss the possible future development of hypomethylating agent-containing combinatory therapeutic strategy for myeloid sarcoma, given its direct anti-leukemic effect and immunomodulatory effect.
Topics: Aged, 80 and over; Azacitidine; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Sarcoma, Myeloid
PubMed: 34148918
DOI: 10.1620/tjem.254.101 -
Modern Pathology : An Official Journal... Apr 2020Myelodysplastic syndrome with isolated del(5q) is a well-recognized entity with a relatively favorable prognosis. Isolated del(5q) in acute myeloid leukemia is rare and... (Comparative Study)
Comparative Study
Acute myeloid leukemia with isolated del(5q) is associated with IDH1/IDH2 mutations and better prognosis when compared to acute myeloid leukemia with complex karyotype including del(5q).
Myelodysplastic syndrome with isolated del(5q) is a well-recognized entity with a relatively favorable prognosis. Isolated del(5q) in acute myeloid leukemia is rare and acute myeloid leukemia cases with isolated del(5q) are not well characterized. Del(5q) has been shown to be a poor prognostic marker in acute myeloid leukemia based on multivariable analysis in large cohort studies, which contained mostly cases with del(5q) in the context of multiple chromosomal abnormalities. To further characterize acute myeloid leukemia with isolated del(5q), clinicopathologic characterization including mutation analysis was performed. During a 10-year period, we identified 12 cases of acute myeloid leukemia with isolated del(5q), 7 cases of acute myeloid leukemia with del(5q) plus one additional chromosome abnormality not involving chromosome 7, as well as two control groups composed of 124 cases of acute myeloid leukemia with complex karyotype including del(5q), and 40 cases of myelodysplastic syndrome with isolated del(5q). At diagnosis, cases of acute myeloid leukemia with isolated del(5q) had higher platelet counts (p = 0.044), hemoglobin (p = 0.011), and mean corpuscular volume (p = 0.017) compared with cases of acute myeloid leukemia with complex karyotype including del(5q). Acute myeloid leukemia with isolated del(5q) was less likely therapy-related (p = 0.037), more likely to have IDH1/IDH2 mutations (p = 0.009), and less likely to have TP53 mutations (p = 0.005) when compared to acute myeloid leukemia with complex karyotype including del(5q). Acute myeloid leukemia with isolated del(5q) also showed longer overall survival than acute myeloid leukemia with complex karyotype cases including del(5q) (p = 0.004). In summary, acute myeloid leukemia with isolated del(5q) appeared to show some distinct clinicopathologic and genomic features as compared to cases of acute myeloid leukemia with complex karyotype including del(5q).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Chromosome Deletion; Chromosomes, Human, Pair 5; Female; Genetic Predisposition to Disease; Humans; Infant; Isocitrate Dehydrogenase; Karyotype; Leukemia, Myeloid, Acute; Male; Middle Aged; Phenotype; Prognosis; Young Adult
PubMed: 31685963
DOI: 10.1038/s41379-019-0396-4 -
The Indian Journal of Medical Research Dec 2016Dysregulation in microRNAs (miRNAs) expression has been observed in distinct acute myeloid leukaemia (AML) subtypes, and their potential as an effective diagnostic and... (Review)
Review
Dysregulation in microRNAs (miRNAs) expression has been observed in distinct acute myeloid leukaemia (AML) subtypes, and their potential as an effective diagnostic and prognostic biomarker is slowly being realized. Certain miRNAs have been found to be associated with various cytogenetic and molecular abnormalities of prognostic significance in AML. Experimental evidences have indicated the potential of modulating miRNA expression as an effective antileukaemic strategy. This has opened a new window for miRNAs-based targeted therapies. In this review, we present results of some studies analyzing the dysregulation in miRNAs expression pattern in paediatric AML and also discuss their use as diagnostic and prognostic markers.
Topics: Biomarkers, Tumor; Child; Gene Expression Profiling; Humans; Leukemia, Myeloid, Acute; MicroRNAs; Prognosis
PubMed: 28474617
DOI: 10.4103/ijmr.IJMR_220_15 -
Hematology. American Society of... Nov 2018We are several years into the "postdiscovery" era in acute myeloid leukemia (AML) thanks to extensive work involving the sequencing of genomes and exomes of countless... (Review)
Review
We are several years into the "postdiscovery" era in acute myeloid leukemia (AML) thanks to extensive work involving the sequencing of genomes and exomes of countless patients, which has led to routine comprehensive targeted sequencing in clinical care. The ability to unlock the molecular underpinnings of each patient's disease was supposed to usher in a new treatment era in which each patient was assigned, based on her mutational profile, a personalized cocktail of targeted therapies that would snuff the disease into submission with minimal toxicity. Whether we have fully realized the promise of personalized therapy in AML is unclear. Here, I review those new drugs that have been inspired by genomics, discuss others that might be possible and their potential roles, and consider whether the ability to target genomic mutations in a personalized manner constitutes the future of AML therapeutics or is representative of an era that has already passed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid, Acute; Mutation; Precision Medicine
PubMed: 30504290
DOI: 10.1182/asheducation-2018.1.45 -
Clinical Cancer Research : An Official... Oct 2022A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by...
PURPOSE
A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC.
PATIENTS AND METHODS
In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers.
RESULTS
Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders.
CONCLUSIONS
The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.
Topics: Antineoplastic Combined Chemotherapy Protocols; Genetic Therapy; Humans; Immune Checkpoint Inhibitors; Radiosurgery; Thymidine; Thymidine Kinase; Triple Negative Breast Neoplasms; Valacyclovir
PubMed: 35877117
DOI: 10.1158/1078-0432.CCR-22-0622 -
British Journal of Haematology Apr 2014Acute myeloid leukaemia (AML) is a heterogeneous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most... (Review)
Review
Acute myeloid leukaemia (AML) is a heterogeneous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most prominent patient-specific risk factor, while chromosomal aberrations are the strongest disease-specific risk factors. For patients with cytogenetically normal AML, prognosis can be specified by mutational status of the genes NPM1, FLT3 and CEBPA. A growing number of recurrent mutations in additional genes have recently been identified, for which the prognostic effect yet has to be determined. Performance status, geriatric assessment, secondary leukaemia following myelodysplastic syndrome or cytotoxic treatment, common laboratory parameters, leukaemic stem cell frequency, bone marrow microenvironment, gene expression levels, epigenetic changes, micro-RNA's as well as kinetics and depth of response to treatment influence prognosis of AML patients. Despite the high number of established risk factors, only few predictive markers exist which can truly aid therapy decisions in patients with AML.
Topics: Adult; Humans; Leukemia, Myeloid, Acute; Nucleophosmin; Prognosis; Risk Factors
PubMed: 24484469
DOI: 10.1111/bjh.12750 -
Blood Jul 1993
Topics: Clone Cells; Dosage Compensation, Genetic; Female; Humans; Leukemia, Myeloid, Acute; Remission Induction
PubMed: 8329693
DOI: No ID Found -
Biology of Blood and Marrow... Jan 2012Acute myeloid leukemia and myelodysplastic syndromes are the most common indications for allogeneic hematopoietic cell transplantation. Although this treatment can be... (Review)
Review
Acute myeloid leukemia and myelodysplastic syndromes are the most common indications for allogeneic hematopoietic cell transplantation. Although this treatment can be curative, even in advanced disease, treatment failure is commonly manifested by relapse of disease, for which treatment is successful in only a minority of patients. There is a necessity for new strategies for prevention of posttransplantation relapse through early disease detection and intervention in order to improve patient outcomes. Detection of minimal residual disease in posttransplantation surveillance is felt to be a necessary component of any strategy. In chronic myeloid leukemia, assessment of the BCR-ABL1 load by quantitative real-time PCR provides an optimal guideline for posttransplantation therapeutic decisions, but in patients with acute myeloid leukemia or myelodysplastic syndromes, the situation is more complex because of the genetic heterogeneity of these disorders. Past strategies for relapse prevention have focused on use of donor lymphocyte infusions with variable success. Peritransplantation and maintenance therapies (eg, azacitidine) are under current investigation. This review summarizes the current status of minimal residual disease monitoring and prevention strategies for both pediatric and adult patients with myeloid malignancies in the transplantation setting and discusses perspectives for further improvement.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Fusion Proteins, bcr-abl; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myeloid, Acute; Male; Monitoring, Physiologic; Neoplasm, Residual; Real-Time Polymerase Chain Reaction; Recurrence; Transplantation, Homologous
PubMed: 22226115
DOI: 10.1016/j.bbmt.2011.10.028 -
Blood Advances Mar 2022
Topics: Hematology; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Prognosis; Tumor Suppressor Protein p53
PubMed: 35090167
DOI: 10.1182/bloodadvances.2021006580 -
Haematologica Feb 2023
Review
Topics: Humans; Leukemia, Myeloid, Acute; Longitudinal Studies
PubMed: 36722401
DOI: 10.3324/haematol.2022.280803