Relationship between Aging and Hematopoietic Cell Transplantation

Cupit-Link, Margaret C; Arora, Mukta; Wood, William A.; Hashmi, Shahrukh K.

doi:10.1016/j.bbmt.2018.08.015

Cited by 14 publications

(12 citation statements)

References 58 publications

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“…Despite rapid advances in understanding disease biology and development of several novel therapies, allogeneic hematopoietic cell transplantation (AHCT) remains an important curative treatment option for these patients. Survival post-transplant depends on disease and patient characteristics [2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation

Kongtim

Hasan

Pérez

et al. 2020

Biology of Blood and Marrow Transplantation

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Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific disease risk group (AML-DRG) and revised our previously developed hematopoietic cell transplant-composite risk (HCT-CR) model by incorporating molecular data and MRD status to predict outcomes of patients with AML. The study included 1414 consecutively treated adult AML patients who received a first AHCT. Patients were randomly assigned into training (n = 944) and validation (n = 470) sets. To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox regression analysis in a training dataset was converted into scores, whereas the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. The AML-DRG was developed by assigning the following scores: 1 point to secondary AML, 1 point to the European Leukaemia-Net adverse genetic risk, 2 points to complete remission with MRD positive/unknown, and 4 points to active disease. These scores were used to generate 3 risk groups of the AML-DRG with significantly different overall survivals. By adding the score for significant patient-related factors (HCT-specific comorbidity index/age), we created 4 risk groups of AML-HCT-CR with distinct survival outcomes. Both the AML-DRG and AML-HCT-CR provided significantly better discriminative capacity compared with the disease risk index, European LeukaemiaNet genetic risk model, and cytogenetic risk model. Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post-transplant.

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Section: Introductionmentioning

confidence: 99%

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation

Kongtim

Hasan

Pérez

et al. 2020

Biology of Blood and Marrow Transplantation

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“…Finally, additional hallmarks of aging such as epigenetic alterations and telomere shortening have been implicated in post-transplant outcomes (56). Recently, several elegant clinical translational studies compared the biologic age of donor with that of the recipient age and showed that there was significant accelerated aging associated with HCT, manifested as a rapid increase of epigenetic age and telomere shortening (57,58).…”

Section: Epigenetic Aging and Telomeresmentioning

confidence: 99%

Immune Reconstitution in the Aging Host: Opportunities for Mechanism-Based Therapy in Allogeneic Hematopoietic Cell Transplantation

2021

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Older patients with hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplantation with encouraging outcomes. While aging-related thymic dysfunction remains a major obstacle to optimal and timely immune reconstitution post- transplantation, recent accumulating evidence has suggested that various aging hallmarks such as cellular senescence, inflamm-aging, and hematopoietic stem cell exhaustion, could also impact immune reconstitution post-transplantation in both thymic-dependent and independent manner. Here we review molecular and cellular aspects of immune senescence and immune rejuvenation related to allogeneic hematopoietic cell transplantation among older patients and discuss potential strategies for mechanism-based therapeutic intervention.

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“…When performing hematopoietic cell transplantation, it is critical to assess the chronological as well as biological age of the patient. The biological age of the cells can be attained by evaluating their clonogenic capacity and telomere length [ 52 ]. The telomere length of autologous CD34 + cells did not have any influence on the clinical outcome in cardiomyopathy patients.…”

Section: Senescence and Its Effect On Stem Cell Biology Transplanmentioning

confidence: 99%

Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

Saheera

Potnuri²,

Krishnamurthy

2020

Cells

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Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell–cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections.

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Relationship between Aging and Hematopoietic Cell Transplantation

Cited by 14 publications

References 58 publications

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation

Immune Reconstitution in the Aging Host: Opportunities for Mechanism-Based Therapy in Allogeneic Hematopoietic Cell Transplantation

Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

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