This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research
Yue Han
First Affiliated Hospital of Soochow University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7560-7195
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Backgroud: Chimeric antigen receptor (CAR) T-cell therapy has shown excellent clinical efficacy in patients with hematologic malignancies. However, severe bleeding after this treatment is a life-threatening complication for most patients.
Objectives: This study evaluated the risk factors associated with bleeding in CAR-T treatment and developed a predictive model for this complication.
Methods: We conducted a real-world study incorporating data from 400 patients with hematologic malignancies treated with CAR-T between November 1, 2015 and September 1, 2019. Also 39 patients from another hospital were selected for external validation.
Results: Patients with severe bleeding (hazard ratio [HR] 13.04, 95% confidence interval [CI] 5.82-29.18; p<0.001) had a higher risk of death after CAR-T. Stage III and IV cytokine release syndrome (CRS) (odds ratio [OR] 6.07, 95% CI 2.35-16.76; p<0.001) and higher tumor necrosis factor-α (TNF-α) levels (OR 4.00, 95% CI 1.53-11.35; p<0.001) were independent factors of bleeding in patients after CAR-T treatment. The predictive model developed by Lasso regression, which selected factors such as CRS period, transfusion volume, platelet percentage, platelet count, thrombinogen time, interleukin 6 and TNF-α levels, and showed Nomogram, yielded excellent agreement (C-statistics=0.905) with the calibration curve, which improved clinical benefit with respect to established bleeding scores such as outpatient bleeding risk index (MOBRI). External validation was performed using 39 patients from another hospital with an AUC of 0.700.
Conclusions: Patients with severe bleeding after Car-T therapy had increased the risk of death. A cross-validated bleeding risk score based on CRS stages and TNF-α level show significant prognostic value in patients undergoing Car-T treatment.
Keywords
CAR T-cell therapy, Bleeding, Cytokine-release syndrome, TNF-α, Prediction model
Figure 1
Figure 1
Figure 1
Figure 2
Figure 2
Figure 2
Figure 3
Figure 3
Figure 3
Figure 4
Figure 4
Figure 4
Figure 5
Figure 5
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.docx
Title of data: Supplemental Materials Description of data: Supplemental Tables and figures, Report of sample size assessment and Details of variants.
- Additionalfile1.docx
Title of data: Supplemental Materials Description of data: Supplemental Tables and figures, Report of sample size assessment and Details of variants.
- Additionalfile1.docx
Title of data: Supplemental Materials Description of data: Supplemental Tables and figures, Report of sample size assessment and Details of variants.
- Additionalfile2.docx
Title of data: TRIPOD_Checklist Description of data: TRIPOD_Checklist for this paper.
- Additionalfile2.docx
Title of data: TRIPOD_Checklist Description of data: TRIPOD_Checklist for this paper.
- Additionalfile2.docx
Title of data: TRIPOD_Checklist Description of data: TRIPOD_Checklist for this paper.
- Additionalfile3.doc
Title of data: STROBE_checklist Description of data: STROBE_checklist for this paper.
- Additionalfile3.doc
Title of data: STROBE_checklist Description of data: STROBE_checklist for this paper.
- Additionalfile3.doc
Title of data: STROBE_checklist Description of data: STROBE_checklist for this paper.
- table11.xlsx
- table11.xlsx
- table11.xlsx
- table21.xlsx
- table21.xlsx
- table21.xlsx
- table31.xlsx
- table31.xlsx
- table31.xlsx
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Hematological Oncology.
No community comments so far
Version 1
Posted 19 Nov, 2020
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Yue Han
First Affiliated Hospital of Soochow University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7560-7195
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Hematological Oncology.
No community comments so far
Version 1
Posted 19 Nov, 2020
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Hematological Oncology.
Backgroud: Chimeric antigen receptor (CAR) T-cell therapy has shown excellent clinical efficacy in patients with hematologic malignancies. However, severe bleeding after this treatment is a life-threatening complication for most patients.
Objectives: This study evaluated the risk factors associated with bleeding in CAR-T treatment and developed a predictive model for this complication.
Methods: We conducted a real-world study incorporating data from 400 patients with hematologic malignancies treated with CAR-T between November 1, 2015 and September 1, 2019. Also 39 patients from another hospital were selected for external validation.
Results: Patients with severe bleeding (hazard ratio [HR] 13.04, 95% confidence interval [CI] 5.82-29.18; p<0.001) had a higher risk of death after CAR-T. Stage III and IV cytokine release syndrome (CRS) (odds ratio [OR] 6.07, 95% CI 2.35-16.76; p<0.001) and higher tumor necrosis factor-α (TNF-α) levels (OR 4.00, 95% CI 1.53-11.35; p<0.001) were independent factors of bleeding in patients after CAR-T treatment. The predictive model developed by Lasso regression, which selected factors such as CRS period, transfusion volume, platelet percentage, platelet count, thrombinogen time, interleukin 6 and TNF-α levels, and showed Nomogram, yielded excellent agreement (C-statistics=0.905) with the calibration curve, which improved clinical benefit with respect to established bleeding scores such as outpatient bleeding risk index (MOBRI). External validation was performed using 39 patients from another hospital with an AUC of 0.700.
Conclusions: Patients with severe bleeding after Car-T therapy had increased the risk of death. A cross-validated bleeding risk score based on CRS stages and TNF-α level show significant prognostic value in patients undergoing Car-T treatment.
Figure 1
Figure 1
Figure 1
Figure 2
Figure 2
Figure 2
Figure 3
Figure 3
Figure 3
Figure 4
Figure 4
Figure 4
Figure 5
Figure 5
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.docx
Title of data: Supplemental Materials Description of data: Supplemental Tables and figures, Report of sample size assessment and Details of variants.
- Additionalfile1.docx
Title of data: Supplemental Materials Description of data: Supplemental Tables and figures, Report of sample size assessment and Details of variants.
- Additionalfile1.docx
Title of data: Supplemental Materials Description of data: Supplemental Tables and figures, Report of sample size assessment and Details of variants.
- Additionalfile2.docx
Title of data: TRIPOD_Checklist Description of data: TRIPOD_Checklist for this paper.
- Additionalfile2.docx
Title of data: TRIPOD_Checklist Description of data: TRIPOD_Checklist for this paper.
- Additionalfile2.docx
Title of data: TRIPOD_Checklist Description of data: TRIPOD_Checklist for this paper.
- Additionalfile3.doc
Title of data: STROBE_checklist Description of data: STROBE_checklist for this paper.
- Additionalfile3.doc
Title of data: STROBE_checklist Description of data: STROBE_checklist for this paper.
- Additionalfile3.doc
Title of data: STROBE_checklist Description of data: STROBE_checklist for this paper.
- table11.xlsx
- table11.xlsx
- table11.xlsx
- table21.xlsx
- table21.xlsx
- table21.xlsx
- table31.xlsx
- table31.xlsx
- table31.xlsx
Loading...