Effect of Smoking on Outcomes of Allogeneic Transplantation: A Single-Center Analysis

Tamaki, Masaharu; Nakasone, Hideki; Kawamura, Masakatsu; Kawamura, Satoshi; Takeshita, Junko; Yoshino, Nozomu; Misaki, Yukiko; Yoshimura, Kazuki; Matsumi, Shinpei; Gomyo, Ayumi; Tanihara, Aki; Kusuda, Machiko; Akahoshi, Yu; Kawamura, Koji; Kimura, Shun‐ichi; Kako, Shinichi; Kanda, Yoshinobu

doi:10.1016/j.bbmt.2020.03.015

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…27 As for male as a risk factor, smoking might affect the outcomes. 34 There are some limitations in this study. First, CMV antigenemia has been used in Japan because of their preference of the health insurance system, whereas real-time PCR has been more commonly used worldwide.…”

Section: Discussionmentioning

confidence: 91%

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Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non‐relapse mortality after allogeneic hematopoietic stem cell transplantation

Takeshita

Kimura

Nakasone

et al. 2021

Transplant Infectious Dis

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Background:We assessed the kinetics of cytomegalovirus (CMV) reactivation using the area under the curve (AUC), which simultaneously reflects both the viral load at each time point and the duration of CMV antigenemia (CMV-AG). Methods:We performed a single-institute retrospective analysis in patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between 2007 and 2017 and survived more than 100 days after HSCT. The AUC of CMV-AG (CMV-AUC) was calculated by a trapezoidal method using the number of CMV-AG tested by the C10/C11 method after logarithmic transformation, and plotted weekly up to day 100.Results: CMV reactivation was observed in 195 cases and the median CMV-AUC for CMV-reactivated patients was 8.7 (range 0.5-30.7). Older age, corticosteroid administration, CMV-seropositive transplant recipients, HSCT from an unrelated donor, and underlying diseases were independent predictive factors for higher CMV-AUC. Higher CMV-AUC was associated with poor overall survival (OS) with borderline significance in a univariate analysis (p = .07), but was not significant in a multivariate analysis. Older age, high-risk disease status, and female gender were identified as significant factors associated with poor OS in this study. On the other hand, CMV-AUC (hazard ratio: no reactivation reference, low 0.98, high 2.49, p < .01), older age, HCT-CI ≥3, and corticosteroid administration were identified as significant factors associated with increased incidence of non-relapse mortality (NRM). Conclusions:The kinetics of CMV reactivation in terms of CMV-AUC reflect both the severity and duration of CMV reactivation. High CMV-AUC was associated with an increased incidence of NRM in survivors over 100 days.

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Section: Discussionmentioning

confidence: 91%

“…Aside from CMV‐AUC, well‐recognized factors such as older age and disease risk were identified as risk factors for poor OS 27 . As for male as a risk factor, smoking might affect the outcomes 34 …”

Section: Discussionmentioning

confidence: 99%

Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non‐relapse mortality after allogeneic hematopoietic stem cell transplantation

Takeshita

Kimura

Nakasone

et al. 2021

Transplant Infectious Dis

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“…Although it has been observed that smokers tend to exhibit reduced posttransplant survival rates and increased mortality following allogeneic HSPC transplantation [30][31][32][33], the potential role of impaired hematopoietic niche function has not been explored in depth. We conducted a comprehensive analysis of the influence of CSE on MSC characteristics and MSC-HSPC interactions.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke impairs the hematopoietic supportive property of mesenchymal stem cells via the production of reactive oxygen species and NLRP3 activation

Park,

Lee,

Chae

et al. 2024

Stem Cell Res Ther

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Background Mesenchymal stem cells (MSCs) play important roles in tissue homeostasis by providing a supportive microenvironmental niche for the hematopoietic system. Cigarette smoking induces systemic abnormalities, including an impeded recovery process after hematopoietic stem cell transplantation. However, the role of cigarette smoking-mediated alterations in MSC niche function have not been investigated. Methods In the present study, we investigated whether exposure to cigarette smoking extract (CSE) disrupts the hematopoietic niche function of MSCs, and pathways impacted. To investigate the effects on bone marrow (BM)-derived MSCs and support of hematopoietic stem and progenitor cells (HSPCs), mice were repeatedly infused with the CSE named 3R4F, and hematopoietic stem and progenitor cells (HSPCs) supporting function was determined. The impact of 3R4F on MSCs at cellular level were screened by bulk-RNA sequencing and subsequently validated through qRT-PCR. Specific inhibitors were treated to verify the ROS or NLRP3-specific effects, and the cells were then transplanted into the animal model or subjected to coculture with HSPCs. Results Both direct ex vivo and systemic in vivo MSC exposure to 3R4F resulted in impaired engraftment in a humanized mouse model. Furthermore, transcriptomic profile analysis showed significantly upregulated signaling pathways related to reactive oxygen species (ROS), inflammation, and aging in 3R4F-treated MSCs. Notably, ingenuity pathway analysis revealed the activation of NLRP3 inflammasome signaling pathway in 3R4F-treated MSCs, and pretreatment with the NLRP3 inhibitor MCC950 rescued the HSPC-supporting ability of 3R4F-treated MSCs. Conclusion In conclusion, these findings indicate that exposure to CSE reduces HSPCs supportive function of MSCs by inducing robust ROS production and subsequent NLRP3 activation.

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Clinical Impact of Pretransplantation Physical Function on Transplantation after Allogeneic Hematopoietic Cell Transplantation in Older Adults

Gomyo,

Kimura,

Suzuki

et al. 2023

Transplantation and Cellular Therapy

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Effect of Smoking on Outcomes of Allogeneic Transplantation: A Single-Center Analysis

Cited by 3 publications

References 31 publications

Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non‐relapse mortality after allogeneic hematopoietic stem cell transplantation

Association between the kinetics of cytomegalovirus reactivation in terms of the area under the curve of cytomegalovirus antigenemia and non‐relapse mortality after allogeneic hematopoietic stem cell transplantation

Cigarette smoke impairs the hematopoietic supportive property of mesenchymal stem cells via the production of reactive oxygen species and NLRP3 activation

Clinical Impact of Pretransplantation Physical Function on Transplantation after Allogeneic Hematopoietic Cell Transplantation in Older Adults

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