-
Best Practice & Research. Clinical... Sep 2013Relapse after achieving a prior response remains one of the most important obstacles to improving the outcome of patients with acute myeloid leukemia (AML). Although... (Review)
Review
Relapse after achieving a prior response remains one of the most important obstacles to improving the outcome of patients with acute myeloid leukemia (AML). Although overall, the majority of patients with disease relapse do poorly, this is by no means uniform and a number of predictors of outcome have been identified. Previously, most trials of investigational agents in the setting of disease relapse in AML have accrued a wide range of patients with widely different patient and disease characteristics. With increased understanding of the biology of the neoplastic change in AML, and better identification of disease subsets based on their molecular characterization, target-specific novel agents are being developed that will hopefully lead to better strategies, not only for treating relapsed disease, but also for the initial induction treatment.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Prognosis; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Salvage Therapy; Standard of Care; Survival Analysis; Transplantation, Homologous
PubMed: 24309527
DOI: 10.1016/j.beha.2013.10.005 -
Haematologica Dec 2022
Topics: Humans; Neoplasm, Residual; Leukemia, Myeloid, Acute; Prognosis; Flow Cytometry
PubMed: 35295082
DOI: 10.3324/haematol.2022.280747 -
Haematologica Apr 2023
Topics: Humans; Leukemia, Myeloid, Acute; Induction Chemotherapy
PubMed: 35861019
DOI: 10.3324/haematol.2022.281506 -
Haematologica Apr 2010
Topics: Humans; Leukemia, Myeloid, Acute; Mutation; Nuclear Proteins; Nucleophosmin
PubMed: 20378574
DOI: 10.3324/haematol.2009.017822 -
Modern Pathology : An Official Journal... Jul 2015The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of...
The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia-not evaluable showed significantly different event-free survival compared with acute myeloid leukemia-not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.
Topics: Adult; Aged; Aged, 80 and over; Cell Shape; Female; Humans; Leukemia, Myeloid, Acute; Male; Megakaryocytes; Middle Aged; Myeloid Cells; Prognosis; Reproducibility of Results; Young Adult
PubMed: 25975285
DOI: 10.1038/modpathol.2015.55 -
Journal of Medical Case Reports Feb 2016Acute myeloid leukemia is typically a disease of the older population and presents mostly in the fifth decade of life. Myeloid sarcoma is a rare initial presentation of... (Review)
Review
BACKGROUND
Acute myeloid leukemia is typically a disease of the older population and presents mostly in the fifth decade of life. Myeloid sarcoma is a rare initial presentation of acute myeloid leukemia. Previously it has only been documented in children and younger patients.
CASE PRESENTATION
We present an unusual case of retro-orbital myeloid sarcoma as an initial presentation of acute myeloid leukemia in a 43-year-old Caucasian man, with rearrangement of chromosome 11q23 involving the MLL gene.
CONCLUSIONS
We present an unusual case of retro-orbital myeloid sarcoma as an initial presentation of acute myeloid leukemia in a 43-year-old man, with rearrangement of chromosome 11q23 involving the MLL gene.
Topics: Adult; Chromosomes, Human, Pair 11; Fatal Outcome; Gene Rearrangement; Histone-Lysine N-Methyltransferase; Humans; Leukemia, Myeloid, Acute; Male; Myeloid-Lymphoid Leukemia Protein; Orbital Neoplasms; Sarcoma, Myeloid
PubMed: 26846095
DOI: 10.1186/s13256-015-0778-2 -
Blood Jun 2022
Topics: Aged; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Neoplasm Recurrence, Local; Transplantation, Homologous; Treatment Outcome
PubMed: 35708721
DOI: 10.1182/blood.2022017070 -
Gut Jun 2018Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to facilitate myeloid cell recruitment from the bone marrow to establish an immunosuppressive tumour...
Targeting both tumour-associated CXCR2 neutrophils and CCR2 macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma.
OBJECTIVE
Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to facilitate myeloid cell recruitment from the bone marrow to establish an immunosuppressive tumour microenvironment (TME). Targeting tumour-associated CXCR2neutrophils (TAN) or tumour-associated CCR2 macrophages (TAM) alone improves antitumour immunity in preclinical models. However, a compensatory influx of an alternative myeloid subset may result in a persistent immunosuppressive TME and promote therapeutic resistance. Here, we show CCR2 and CXCR2 combined blockade reduces total tumour-infiltrating myeloids, promoting a more robust antitumour immune response in PDAC compared with either strategy alone.
METHODS
Blood, bone marrow and tumours were analysed from PDAC patients and controls. Treatment response and correlative studies were performed in mice with established orthotopic PDAC tumours treated with a small molecule CCR2 inhibitor (CCR2i) and CXCR2 inhibitor (CXCR2i), alone and in combination with chemotherapy.
RESULTS
A systemic increase in CXCR2 TAN correlates with poor prognosis in PDAC, and patients receiving CCR2i showed increased tumour-infiltrating CXCR2 TAN following treatment. In an orthotopic PDAC model, CXCR2 blockade prevented neutrophil mobilisation from the circulation and augmented chemotherapeutic efficacy. However, depletion of either CXCR2 TAN or CCR2 TAM resulted in a compensatory response of the alternative myeloid subset, recapitulating human disease. This was overcome by combined CCR2i and CXCR2i, which augmented antitumour immunity and improved response to FOLFIRINOX chemotherapy.
CONCLUSION
Dual targeting of CCR2 TAM and CXCR2 TAN improves antitumour immunity and chemotherapeutic response in PDAC compared with either strategy alone.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Databases, Factual; Flow Cytometry; Humans; Immunohistochemistry; Immunomodulation; Macrophages; Mice; Mice, Inbred C57BL; Myeloid Cells; Neutrophil Infiltration; Neutrophils; Pancreatic Neoplasms; Real-Time Polymerase Chain Reaction; Receptors, CCR2; Receptors, Interleukin-8B; Tissue Array Analysis; Tumor Microenvironment
PubMed: 29196437
DOI: 10.1136/gutjnl-2017-313738 -
Blood Mar 1970
Topics: Adult; Antineoplastic Agents; Autopsy; Biopsy; Breast Neoplasms; Cheek; Diagnosis, Differential; Facial Neoplasms; Female; Humans; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Sarcoma; Thoracic Neoplasms
PubMed: 4908654
DOI: No ID Found -
The Western Journal of Medicine Jan 1978
Topics: Aged; Diagnosis, Differential; Humans; Leukemia, Myeloid, Acute; Preleukemia; Prognosis
PubMed: 272807
DOI: No ID Found