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. 2022 May 11;49(3):143-157.
doi: 10.1159/000524538. eCollection 2022 Jun.

Safety of Intraoperative Cell Salvage in Cancer Surgery: An Updated Meta-Analysis of the Current Literature

Thomas Frietsch  1 , Andrea U Steinbicker  2 , Audrey Horn  3 , Matthes Metz  4 , Gerald Dietrich  5 , Markus A Weigand  6 , Jonathan H Waters  7 , Dania Fischer  6
Affiliations

Safety of Intraoperative Cell Salvage in Cancer Surgery: An Updated Meta-Analysis of the Current Literature

Thomas Frietsch et al. Transfus Med Hemother. .

Abstract

Background: Allogeneic blood transfusions in oncologic surgery are associated with increased recurrence and mortality. Adverse effects on outcome could be reduced or avoided by using intraoperative autologous blood cell salvage (IOCS). However, there are concerns regarding the safety of the autologous IOCS blood. Previous meta-analyses from 2012 and 2020 did not identify increased risk of cancer recurrence after using autologous IOCS blood. The objective of this review was to reassess a greater number of IOCS-treated patients to present an updated and more robust analysis of the current literature.

Methods: This systematic review includes full-text articles listed in PubMed, Cochrane, Cochrane Reviews, and Web of Science. We analyzed publications that discussed cell salvage or autotransfusion combined with the following outcomes: cancer recurrence, mortality, survival, allogeneic transfusion rate and requirements, length of hospital stay (LOS). To rate the strength of evidence, a Grading of Recommendations Assessment, Development and Evaluation (GRADE) of the underlying evidence was applied.

Results: In the updated meta-analysis, 7 further observational studies were added to the original 27 observational studies included in the former 2020 analysis. Studies compared either unfiltered (n = 2,311) or filtered (n = 850) IOCS (total n = 3,161) versus non-IOCS use (n = 5,342). Control patients were either treated with autologous predonated blood (n = 484), with allogeneic transfusion (n = 4,113), or did not receive a blood transfusion (n = 745). However, the current literature still contains only observational studies on these topics, and the strength of evidence remains low. The risk of cancer recurrence was reduced in recipients of autologous salvaged blood with or without LDF (odds ratio [OR] 0.76, 95% confidence interval [CI]: 0.64-0.90) compared to nontransfused patients or patients with allogeneic transfusion. There was no difference in mortality (OR 0.95, 95% CI: 0.71-1.27) and LOS (mean difference -0.07 days, 95% CI: -0.63 to 0.48) between patients treated with IOCS blood or those in whom IOCS was not used. Due to high heterogeneity, transfusion rates or volumes could not be analyzed.

Conclusion: Randomized controlled trials comparing mortality and cancer recurrence rate of IOCS with or without LDF filtration versus allogeneic blood transfusion were not found. Outcome was similar or better in patients receiving IOCS during cancer surgery compared to patients with allogeneic blood transfusion or nontransfused patients.

Keywords: Autologous transfusion; Cancer recurrence; Cell salvage; Tumor surgery.

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Conflict of interest statement

T.F.: honoraria and reimbursements for travel expenses, lectures, investigator meetings, and presentations from Janssen-Cilag, AstraZeneca, Vifor Pharma, Pharmacosmos, the German Red Cross, Aspect Medical, Organon, Alliance Pharmaceuticals, and Baxter Healthcare Corp; expert consulting contracts with Janssen-Cilag, Vifor Pharma, Pharmacosmos; research grants from the Else-Groenert-Foundation and the University Medicine Mannheim, University of Heidelberg. A.U.S.: research grant from Pharmacosmos, Denmark, to perform a single-center, prospective trial on preoperative anemia treatment. A.U.S. is supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) grant STE 1895/9-1 and STE 1895/10-1 as part of the DFG research consortium FerrOS-FOR5146. A.H.: no conflicts of interest to declare. M.M.: no conflicts of interest to declare. G.D.: no conflicts of interest to declare. M.A.W.: no conflicts of interest to declare. J.H.W.: no conflicts of interest to declare. D.F.: no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Systematic research history − Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow. The numbers of studies does not sum up due to the report of more than one outcome per study. n, numbers of publications; LOS, length of hospital stay.
Fig. 2
Fig. 2
Forest plot for all studies that reported cancer recurrence. Twenty-five studies compared n = 2,126 subjects treated with IOCS versus n = 3,742 controls. The weight of a single study in the meta-analysis is reflected by the size of the blue square (and dependent from number of subjects and width of CIs). The horizontal lines are confidential intervals. The length of follow-up is not displayed (for this see Table 1). Control groups were mentioned as “no IOCS use” without further details (n = 3,283) or specified as allogeneic transfusion (n = 358), PAD with or without allogeneic blood (n = 394), or no transfusion necessary (n = 125).
Fig. 3
Fig. 3
Forest plot for all studies that reported mortality. Twenty studies compared n = 1,537 subjects treated with IOCS versus n = 3,091 controls. The weight of a single study in the meta-analysis is reflected by the size of the blue square (and dependent from number of subjects and width of CIs). The horizontal lines are confidential intervals. The length of follow-up is not displayed (for this see Table 1). Control groups were mentioned as “no IOCS use” without further details (n = 2,729) or specified as allogeneic transfusion (n = 64), PAD with or without allogeneic blood (n = 105), or no transfusion necessary (n = 91).
Fig. 4
Fig. 4
Forest plot for all studies that reported the transfusion rate (numbers of subjects transfused per group). Nineteen studies compared n = 1,629 subjects treated with IOCS versus n = 3,646 controls. The weight of a single study in the meta-analysis is reflected by the size of the blue square (and dependent from the number of subjects and width of CIs). The length of follow-up is not displayed (for this see Table 1). Heterogeneity I2 = 87% prohibits reliable calculation of OR. Control groups were mentioned as “no IOCS use” without further details (n = 3,287) or specified as allogeneic transfusion (n = 80), PAD with or without allogeneic blood (n = 140), or no transfusion necessary (n = 57).
Fig. 5
Fig. 5
Forest plot for all studies that reported transfusion requirements (number of transfused volumes/units per group). Ten studies compared n = 842 subjects treated with IOCS versus n = 860 controls. The weight of a single study in the meta-analysis is reflected by the size of the blue square (and dependent from the number of subjects and width of CIs). Horizontal lines are confidential intervals. The length of follow-up is not displayed (for this see Table 1). Heterogeneity I2 = 100% prohibits reliable calculation of OR. Control groups were mentioned as “no IOCS use” without further details (n = 1,116) or specified as allogeneic transfusion (n = 16), PAD with or without allogeneic blood (n = 140) or no transfusion necessary (n = 125).
Fig. 6
Fig. 6
Forest plot for all studies that reported LOS. Studies with nonpositive values for standard deviations were not included in the meta-analysis. Ten studies compared n = 401 subjects treated with IOCS versus n = 576 controls. The weight of a single study in the meta-analysis is reflected by the size of the blue square (and dependent from the number of subjects and width of CIs). The horizontal lines are confidential intervals. The length of follow-up is not displayed (for this see Table 1). Control groups were mentioned as “no IOCS use” without further details (n = 483) or specified as allogeneic transfusion (n = 87), PAD with or without allogeneic blood (n = 95), or no transfusion necessary (n = 0).
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