Acute myeloid leukaemia in patients we judge as being older and/or unfit

Lazarevic, Vladimir

doi:10.1111/joim.13293

Cited by 13 publications

(9 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been known that elderly AML patients (>60-year-old) are usually in a refractory status. Advanced age usually overlaps with a number of undesirable characteristics, such as worse performance status, comorbidities, poor-risk cytogenetics, and organ impairment; hence, they are not endurable to conventional chemotherapies and not able to receive allogeneic hematopoietic stem cell transplantation (HSCT). , The present investigation was conducted in the refractory AML mouse model and obtained encouraging prolonged survival time, strongly suggesting that the antagonistic peptide provide a promising option to the refractory AML treatment by non-cytotoxic mechanisms. It was noticeable that among the tested dosages, 2.5 mg/kg m PO-6 was able to prolong the survival of the AML mice as monotherapeutics, while in this AML model, the first-line chemotherapeutics cytarabine could not induce effective responses …”

Section: Discussionmentioning

confidence: 72%

CD123 Antagonistic Peptides Assembled with Nanomicelles Act as Monotherapeutics to Combat Refractory Acute Myeloid Leukemia

Zhang

Fang

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Due to the development of drug resistance to traditional chemotherapies and high relapse rate, AML still has a low survival rate and there is in an urgent need for better treatment strategies. CD123 is widely expressed by AML cells, also associated with the poor prognosis of AML. In this study, we fabricated nanomicelles loaded with a lab-designed CD123 antagonistic peptide, which were referred to as mPO-6. The antagonistic and therapeutic effects were investigated with CD123+ AML cell lines and a refractory AML mouse (AE and CKITD816V) model. Results show that mPO-6 can specifically bind to the CD123+ AML cells and inhibit the cell viability effectively. Intravenous administration of mPO-6 significantly reduces the percentage of AML cells’ infiltration and prolongs the median survival of AML mice. Further, the efficiency of mPO-6 is demonstrated to interfere with the axis of CD123/IL-3 via regulating the activation of STAT5, PI3K/AKT, and NF-κB signaling pathways related to cell proliferation or apoptosis at the level of mRNA and protein in vivo and in vitro. In conclusion, the novel CD123 antagonistic peptide micelle formulation mPO-6 can significantly enhance apoptosis and prolong the survival of AML mice by effectively interfering with the axis of CD123/IL-3 and therefore is a promising therapeutic candidate for the treatment of refractory AML.

show abstract

Section: Discussionmentioning

confidence: 72%

CD123 Antagonistic Peptides Assembled with Nanomicelles Act as Monotherapeutics to Combat Refractory Acute Myeloid Leukemia

Zhang

Fang

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…Age-dependent differences are probably the explanation as to why several forms of anticancer treatment cannot be used in elderly individuals. Toxic effects and especially hematological toxicity, often dose-limiting for anticancer treatment [214], as well as immune-related toxicity are more severe in allogeneic stem cell transplantation both when using elderly stem cell donors [215][216][217] and for elderly recipients [218,219]. The same may be true for radiation therapy, and in our opinion an increased mortality similar to the mortality in orthopedic surgery [164][165][166] would also be expected for cancer surgery.…”

Section: Carcinogenesis and Cancer Treatment In Elderly Individualsmentioning

confidence: 72%

Hematopoiesis, Inflammation and Aging—The Biological Background and Clinical Impact of Anemia and Increased C-Reactive Protein Levels on Elderly Individuals

Bruserud

Reikvam

2022

JCM

View full text Add to dashboard Cite

Anemia and systemic signs of inflammation are common in elderly individuals and are associated with decreased survival. The common biological context for these two states is then the hallmarks of aging, i.e., genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Such aging-associated alterations of hematopoietic stem cells are probably caused by complex mechanisms and depend on both the aging of hematopoietic (stem) cells and on the supporting stromal cells. The function of inflammatory or immunocompetent cells is also altered by aging. The intracellular signaling initiated by soluble proinflammatory mediators (e.g., IL1, IL6 and TNFα) is altered during aging and contributes to the development of both the inhibition of erythropoiesis with anemia as well as to the development of the acute-phase reaction as a systemic sign of inflammation with increased CRP levels. Both anemia and increased CRP levels are associated with decreased overall survival and increased cardiovascular mortality. The handling of elderly patients with inflammation and/or anemia should in our opinion be individualized; all of them should have a limited evaluation with regard to the cause of the abnormalities, but the extent of additional and especially invasive diagnostic evaluation should be based on an overall clinical evaluation and the possible therapeutic consequences.

show abstract

“…The 3-year OS, CIR, and TRM in our cohort were comparable with those reported in previous studies 1 , 7 , 8 , and no significant difference was found between each age group ( Figure 1A-C ). Generally, patients ≥60 years old are often regarded as the “ elderly ” 19 , but when they are divided into three groups according to age, it is different. The effect of disease status prior to allo-SCT on OS declined with group age, and a significant difference was no longer observed between the CR and non-CR groups in 65-69 and ≥ 70 years old patients.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of allogeneic stem cell transplantation for patients with hematologic diseases ≥60 years old

2023

BCT

View full text Add to dashboard Cite

Hematologic diseases frequently affect people >60 years old, and allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for these patients. Although several multicenter studies proposed the risk assessment of allo-SCT for the elderly, they receive different treatments and management at each facility. Therefore, accumulating data from institutions that exhibit relatively the same treatment policy and patient care is important. This retrospective study aimed to clarify the prognostic factors of allo-SCT for the elderly in our institution. Of the 104 patients, 51.0% were 60-64 years old, and 49.0% were ≥ 65 years old. The 3-year overall survival (OS) was 40.9% and 35.7% for patients 60-64 and ≥ 65 years old, respectively, which is not significant. While the disease status prior to allo-SCT demonstrated strong effects on the 3-year OS for patients that are 60-64 years old (in remission, 76.9%; non-remission, 15.7%, p <0.001), this effect was smaller for patients ≥ 65 years old (in remission, 43.1%; non-remission, 30.1%, p =0.048). Multivariate analysis revealed that the performance status (PS), not the disease status prior to allo-SCT, was the prognostic risk factor of OS for patients aged ≥ 65 years. Our data suggest that PS is a useful predictor of better OS following allo-SCT, especially for patients ≥ 65 years old.

show abstract

Acute myeloid leukaemia in patients we judge as being older and/or unfit

Abstract: Acute myeloid leukaemia in patients we judge as being older and/ or unfit (Review).

Cited by 13 publications

References 88 publications

CD123 Antagonistic Peptides Assembled with Nanomicelles Act as Monotherapeutics to Combat Refractory Acute Myeloid Leukemia

CD123 Antagonistic Peptides Assembled with Nanomicelles Act as Monotherapeutics to Combat Refractory Acute Myeloid Leukemia

Hematopoiesis, Inflammation and Aging—The Biological Background and Clinical Impact of Anemia and Increased C-Reactive Protein Levels on Elderly Individuals

Outcomes of allogeneic stem cell transplantation for patients with hematologic diseases ≥60 years old

Contact Info

Product

Resources

About