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180 The effect of packed red blood cell transfusions on the clinical efficacy of immunotherapy
  1. Christopher D’Avella1,
  2. Karthik Devarajan2,
  3. Martin Edelman2 and
  4. Daniel Geynisman2
  1. 1The University of Pennsylvania, Philadelphia, PA, USA
  2. 2Fox Chase Cancer Center, Philadelphia, PA, USA


Background Transfusions of packed red blood cells (PRBC) have been postulated to be immunosuppressive, an effect known as transfusion-related immunomodulation (TRIM). TRIM is thought to be a result of the immunosuppressive and pro inflammatory effects of residual leukocytes, apoptotic cells, inflammatory mediators, micro particles and free hemoglobin1 Prior studies have shown a negative association between perioperative PRBC transfusions and overall mortality in multiple malignancies.2–13 To date there are no studies addressing the impact of transfusions on survival in patients undergoing treatment with checkpoint inhibitor (CPI) immunotherapy. We conducted a retrospective study to investigate the clinical outcomes associated with PRBC transfusions in patients with non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC) who received immunotherapy for advanced/metastatic disease.

Methods From January 2010 - June 2019, patients at Fox Chase Cancer Center who received a PRBC transfusion within 120 days of treatment with a CPI and with advanced NSCLC, UC and RCC were included. Patient demographics including age, sex, ethnicity, race, tobacco use and ECOG performance status (PS) were abstracted. We also assessed previous chemotherapy, radiation and targeted therapy utilization among all patients. The primary endpoints were progression free survival (PFS) and overall survival (OS) in those who have and have not received PRBCs. We then evaluated PFS and OS via a cox proportional hazards model that was adjusted for cancer type, age, PS, previous therapies and tobacco use.

Results 304 patients including 272 NSCLC, 24 UC and 8 RCC subjects were evaluated. 54 patients underwent a minimum of one PRBC transfusion during the pre-specified time period. Both median PFS (8.2 months versus 3.9) and overall survival (26.1 months versus 13.8) were shorter in patients who underwent transfusion. After multivariable adjustment, the negative associations between transfusion and PFS (HR: 1.53, p=0.03) and overall survival (HR: 1.40, p=0.09) were preserved (figure 1–2). A sub-analysis of the NSCLC patients was conducted and shorter PFS (HR:1.58, p=0.03) and overall survival (HR:1.56, P=0.03) were again seen in the transfusion cohort (figure 3–4).

Abstract 180 Figure 1

Progression free survival. Y refers to transfused population. N refers to non transfused population.

Abstract 180 Figure 2

Overall survival. Y refers to transfused population. N refers to non transfused population.

Abstract 180 Figure 3

Progression free survival in non-small cell lung cancer patients. Y refers to transfused population. N refers to non transfused population

Abstract 180 Figure 4

Overall survival in non-small cell lung cancer patients. Y refers to transfused population. N refers to non transfused population

Conclusions PRBC transfusions led to an inferior PFS and OS in advanced cancer patients receiving checkpoint inhibitors even after adjustments for multiple prognostic variables. These results suggest a possible attenuation of the effectiveness of immunotherapy as a result of the immunosuppressive effects of PRBC transfusions. The findings require prospective and mechanistic confirmation as inherent bias may exist in this retrospective analysis.

Ethics Approval This study was approved the institutional review board at Fox Chase Cancer Center, approval number 19-9006.

Consent N/A


  1. Goubran H, Sheridan D, Radosevic J, Burnouf T, and Seghatchian J, Transfusion-related immunomodulation and cancer. Transfusion and Apheresis Science 2017;56:336–340.

  2. Acheson AG, Brookes MJ, and Spahn DR. Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery. Ann Surg 2012; 256:235–244.

  3. Morgan TM, et al., The relationship between perioperative blood transfusion and overall mortality in patients undergoing radical cystectomy for bladder cancer. Urol. Oncol. Semin. Orig. Investig 2013;31:871–877.

  4. Linder, et al., The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur. Urol. 2013;63:839–45.

  5. Luan H, Ye F, Wu L, Zhou Y, and Jiang J. Perioperative blood transfusion adversely affects prognosis after resection of lung cancer: A systematic review and a meta-analysis. BMC Surgery 2014; 14:34.

  6. Lee J, Chin J-H, Kim J-I, Lee E-H, and Choi I-C. Association between red blood cell transfusion and long-term mortality in patients with cancer of the esophagus after esophagectomy. Dis. esophagus Off. J. Int. Soc. Dis. Esophagus 2017;31:1–8.

  7. Sun C, Wang Y, Yao HS, and Hu ZQ. Allogeneic blood transfusion and the prognosis of gastric cancer patients: systematic review and meta-analysis. Int. J. Surg 2015;13:102–110.

  8. Wang T, et al. Perioperative blood transfusion is associated with worse clinical outcomes in resected lung cancer. Ann. Thorac. Surg 2014;97:1827–1837.

  9. Abu-Ghanem Y, Zilberman DE, Dotan Z, Kaver I, and Ramon J. Perioperative blood transfusion adversely affects prognosis after nephrectomy for renal cell carcinoma. Urol. Oncol 2018;36:12–20.

  10. Pang Q-Y, An R, and Liu H-L, Perioperative transfusion and the prognosis of colorectal cancer surgery: a systematic review and meta-analysis. World J. Surg. Oncol 2019;17:1–11.

  11. Lopez-Aguiar AG, et al., Association of perioperative transfusion with survival and recurrence after resection of gallbladder cancer: a 10-institution study from the us extrahepatic biliary malignancy consortium. J. Surg. Oncol. 2018;117:1638–1647.

  12. Reeh M, et al., Allogenic blood transfusion is associated with poor perioperative and long-term outcome in esophageal cancer. World J. Surg 2017;41:208–215.

  13. Moschini M, et al. The impact of perioperative blood transfusion on survival of bladder cancer patients submitted to radical cystectomy: role of anemia status. Eur. Urol. Focus. 2016;2:86–91.

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