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Journal of Experimental & Clinical... Oct 2023Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible... (Review)
Review
Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all" treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine.The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach.Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a "tailored" therapeutic approach based also on engineered CAR-T cells.
Topics: Humans; Receptors, Chimeric Antigen; Single-Cell Gene Expression Analysis; Leukemia, Myeloid, Acute; Cytarabine; Recurrence
PubMed: 37803464
DOI: 10.1186/s13046-023-02841-8 -
International Journal of Molecular... Feb 2024Minimal residual disease (MRD) is of major importance in onco-hematology, particularly in acute myeloid leukemia (AML). MRD measures the amount of leukemia cells... (Review)
Review
Minimal residual disease (MRD) is of major importance in onco-hematology, particularly in acute myeloid leukemia (AML). MRD measures the amount of leukemia cells remaining in a patient after treatment, and is an essential tool for disease monitoring, relapse prognosis, and guiding treatment decisions. Patients with a negative MRD tend to have superior disease-free and overall survival rates. Considerable effort has been made to standardize MRD practices. A variety of techniques, including flow cytometry and molecular methods, are used to assess MRD, each with distinct strengths and weaknesses. MRD is recognized not only as a predictive biomarker, but also as a prognostic tool and marker of treatment efficacy. Expected advances in MRD assessment encompass molecular techniques such as NGS and digital PCR, as well as optimization strategies such as unsupervised flow cytometry analysis and leukemic stem cell monitoring. At present, there is no perfect method for measuring MRD, and significant advances are expected in the future to fully integrate MRD assessment into the management of AML patients.
Topics: Humans; Neoplasm, Residual; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Recurrence; Flow Cytometry
PubMed: 38396825
DOI: 10.3390/ijms25042150 -
Journal of Pediatric Hematology/oncology Oct 2023B-cell acute lymphoblastic leukemia is the most common type of leukemia found in children. Timely diagnosis, white blood cell count, age of onset, and sex are considered...
B-cell acute lymphoblastic leukemia is the most common type of leukemia found in children. Timely diagnosis, white blood cell count, age of onset, and sex are considered the most important prognostic factors in childhood leukemia. Hematological and biochemical profiles are crucially important to infer the health of leukemia patient pre-chemotherapy and post-chemotherapy treatment. In the current study 200 cases were taken and evaluated for hematological (complete blood count and white blood differential count) and biochemical parameters (renal function tests, liver function tests, serum electrolytes and serum proteins) by comparison with normal reference values. Most of the cases were male under 5 years of age. Hematology parameters including red blood cells, hemoglobin and platelet levels were relatively low whereas white blood cells level was high in cases as compared with normal reference value. Sex-wise and age-wise comparison of biochemical profile showed significant difference among B-cell acute lymphoblastic leukemia cases whereas hematological profile did not show any visible difference.
Topics: Humans; Child; Male; Female; Prognosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Hematology
PubMed: 37526363
DOI: 10.1097/MPH.0000000000002715 -
Blood Mar 2024We show that red cell exchange (RCE) treats hyperleukocytosis in acute leukemia. RCE provided similar leukoreduction to standard therapeutic leukoreduction and could be...
We show that red cell exchange (RCE) treats hyperleukocytosis in acute leukemia. RCE provided similar leukoreduction to standard therapeutic leukoreduction and could be superior in patients with severe anemia or monocytic leukemias or when requiring rapid treatment.
Topics: Adult; Humans; Leukostasis; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Acute Disease; Leukapheresis; Leukocytosis
PubMed: 38052031
DOI: 10.1182/blood.2023021895 -
Current Hematologic Malignancy Reports Dec 2023Largely, treatment advances in relapsed and/or refractory acute lymphoblastic leukemia (ALL) have been made in B cell disease leaving T cell ALL reliant upon... (Review)
Review
PURPOSE OF REVIEW
Largely, treatment advances in relapsed and/or refractory acute lymphoblastic leukemia (ALL) have been made in B cell disease leaving T cell ALL reliant upon high-intensity chemotherapy. Recent advances in the understanding of the biology of T-ALL and the improvement in immunotherapies have led to new therapeutic pathways to target and exploit. Here, we review the more promising pathways that are able to be targeted and other therapeutic possibilities for T-ALL.
RECENT FINDINGS
Preclinical models and early-phase clinical trials have shown promising results in some case in the treatment of T-ALL. Targeting many different pathways could lead to the next advancement in the treatment of relapsed and/or refractory disease. Recent advances in cellular therapies have also shown promise in this space. When reviewing the literature as a whole, targeting important pathways and antigens likely will lead to the next advancement in T-ALL survival since intensifying chemotherapy.
Topics: Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Immunotherapy; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; T-Lymphocytes; Lymphoma; Lymphoma, T-Cell
PubMed: 37490229
DOI: 10.1007/s11899-023-00706-7 -
Blood Jul 2023
Topics: Humans; Leukemia, Myeloid, Acute; Genomics
PubMed: 37410505
DOI: 10.1182/blood.2023020672 -
Hematology (Amsterdam, Netherlands) Dec 2023This study aims to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aims to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8.
METHODS
A retrospective analysis was conducted on 244 patients with primary acute leukemia with trisomy 8 who received treatment in our hospital, and they were randomly divided into the modeling group (122 cases, including 78 cases with good prognosis and 44 cases with poor prognosis) and the verification group (122 cases). R software was used to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8.
RESULTS
The results of multivariate analysis showed that age >51 years old, and white blood cell count ≤20 × 10/L were risk factors for poor prognosis in acute leukemia patients with trisomy 8 ( < 0.05), and chemotherapy + transplantation was a protective factor for poor prognosis in acute leukemia patients with trisomy 8 ( < 0.05). The nomogram for poor prognosis of acute leukemia patients with trisomy 8 was constructed using the above four risk predictors. The Hosmer-Lemeshow goodness of fit test was = 6.371, = 0.497, and the area under the ROC curve was 0.817 (95%CI: 0.742-0.892). The slope of the calibration curve of external validation was close to 1, Hosmer-Lemeshow goodness of fit test was = 6.507, = 0.448, and the area under the ROC curve was 0.834 (95%CI: 0.748-0.921).
CONCLUSION
The nomogram model constructed in this study for predicting poor prognosis among acute leukemia patients with trisomy 8 demonstrates excellent discrimination and consistency.
Topics: Humans; Middle Aged; Prognosis; Nomograms; Retrospective Studies; Acute Disease; Leukemia, Myeloid, Acute
PubMed: 37545412
DOI: 10.1080/16078454.2023.2240131 -
Bidirectional interplay between metabolism and epigenetics in hematopoietic stem cells and leukemia.The EMBO Journal Dec 2023During the last decades, remarkable progress has been made in further understanding the complex molecular regulatory networks that maintain hematopoietic stem cell (HSC)... (Review)
Review
During the last decades, remarkable progress has been made in further understanding the complex molecular regulatory networks that maintain hematopoietic stem cell (HSC) function. Cellular and organismal metabolisms have been shown to directly instruct epigenetic alterations, and thereby dictate stem cell fate, in the bone marrow. Epigenetic regulatory enzymes are dependent on the availability of metabolites to facilitate DNA- and histone-modifying reactions. The metabolic and epigenetic features of HSCs and their downstream progenitors can be significantly altered by environmental perturbations, dietary habits, and hematological diseases. Therefore, understanding metabolic and epigenetic mechanisms that regulate healthy HSCs can contribute to the discovery of novel metabolic therapeutic targets that specifically eliminate leukemia stem cells while sparing healthy HSCs. Here, we provide an in-depth review of the metabolic and epigenetic interplay regulating hematopoietic stem cell fate. We discuss the influence of metabolic stress stimuli, as well as alterations occurring during leukemic development. Additionally, we highlight recent therapeutic advancements toward eradicating acute myeloid leukemia cells by intervening in metabolic and epigenetic pathways.
Topics: Humans; Hematopoietic Stem Cells; Leukemia; Cell Differentiation; Bone Marrow; Epigenesis, Genetic
PubMed: 38010205
DOI: 10.15252/embj.2022112348 -
American Journal of Obstetrics and... Jan 2024With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through...
BACKGROUND
With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias.
OBJECTIVE
This study aimed to investigate the safety of performing autologous ovarian tissue transplantation in survivors of acute leukemia.
STUDY DESIGN
Clinical, histopathological, and molecular data of 4 women with acute myeloid leukemia and 2 women with acute lymphoblastic leukemia who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66% to 100% of an ovarian cortex with a slow freezing method, all women received high-dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Before the ovarian tissue transplantation, (1) antral follicle counts, serum antimüllerian hormone and follicle-stimulating hormone levels were assessed to confirm primary ovarian insufficiency; (2) all recipients were cleared by their hematologist-oncologists; (3) representative cortical strips were screened for leukemia infiltration by histologic (hematoxylin and eosin staining), immunohistochemical (CD3, CD20, CD34, CD68, CD117, CD163, PAX-5, Tdt, lysozyme, and MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate.
RESULTS
The median age was 20 years (interquartile range, 15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction or consolidation chemotherapy that included cytarabine + daunorubicin or Berlin-Frankfurt-Munich-95 protocol and were in remission. The mean serum antimüllerian hormone was 1.9±1.7 ng/mL before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (interquartile range, 41-120) after ovarian tissue cryopreservation. Ovarian function resumed in all patients after a median of 3.0 months (range, 2.5-4.0), and 2 women had 1 live birth each. The median graft longevity was 35.5 months (interquartile range, 18-57) after ovarian tissue transplantation. After a median follow-up of 51 months (interquartile range, 20-74), all patients remained relapse-free. In 1 patient, the graft was removed during cesarean delivery and was negative for immunochemical leukemia markers.
CONCLUSION
Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by nongonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy before allogeneic hematopoietic stem cell transplantation.
Topics: Pregnancy; Humans; Female; Young Adult; Adult; Anti-Mullerian Hormone; Ovary; Cryopreservation; Fertility Preservation; Leukemia, Myeloid, Acute
PubMed: 37666382
DOI: 10.1016/j.ajog.2023.08.032 -
British Journal of Haematology Dec 2023
Review
Topics: Humans; Aged; Leukemia, Myeloid, Acute; Neoplasm, Residual
PubMed: 37822071
DOI: 10.1111/bjh.19135