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Low Total Lymphocyte Count Is Associated with Poor Survival in Patients with Resected Pancreatic Adenocarcinoma Receiving a GM-CSF Secreting Pancreatic Tumor Vaccine

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Low total lymphocyte count (TLC) and lymphocyte-to-neutrophil ratio have been found to be poor prognostic indicators in several different tumor types at various stages. Although immune-based therapies are under rapid development, it is not known whether baseline complete blood counts, particularly lymphocytes, are associated with the clinical outcomes of patients receiving immunotherapies.

Methods

We performed a retrospective analysis of complete blood count for 59 patients enrolled onto a phase II trial evaluating the integration of an adjuvant immunotherapy—irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine (GVAX)—with standard chemoradiation.

Results

After adjusting for nodal status, individuals with a TLC of <1,500 cells/mm3 (10 patients) had significantly higher risk, both in terms of overall survival (OS) [adjusted hazard ratio 2.63, 95 % confidence interval (CI) 1.22–5.67, p = 0.013] and progression-free survival (adjusted hazard ratio 3.07, 95 % CI 1.03–6.93, p = 0.003), compared to those with a TLC of ≤1,500 cells/mm3 (49 patients). Adjuvant chemoradiation significantly reduced lymphocyte counts from baseline values. Patients with suppression of their lymphocytes to <500 cells/mm3 after chemoradiation also had shorter disease-free and OS.

Conclusions

Immunosuppressive conditions associated with surgical procedures and chemoradiation may affect the efficacy of immunotherapy.

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Acknowledgment

This study was supported by the NCI SPORE in Gastrointestinal Cancers P50 CA062924-14 (E. M. J.), Viragh Foundation (D. L., E. M. J., E. A. S), NIH K23 CA93566 (D. L.), the Sol Goldman Pancreatic Cancer Center (L. Z.), NIH K23 CA148964 (L. Z.) and a Johns Hopkins University School of Medicine Clinician Scientist Award (L. Z.). Dr. Jaffee is the first recipient of the Dana and Albert “Cubby” Broccoli Endowed Professorship.

Disclosure

Under a licensing agreement between Aduro BioTech and the Johns Hopkins University, Dr. Jaffee and the university are entitled to milestone payments and royalty on sales of the vaccine product described in this article. We do not have any other relevant conflicts of interest to be disclosed.

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Author notes

  1. Barish H. Edil MD

    Present address: Pancreas and Biliary Surgery Program, Department of Surgery, University of Colorado, Aurora, CO, USA

Authors and Affiliations

  1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elizabeth A. Sugar PhD, Jennifer Uram PhD, Elaine Bigelow BS, Joseph M. Herman MD, Barish H. Edil MD, Elizabeth M. Jaffee MD, Lei Zheng MD, PhD & Daniel A. Laheru MD

  2. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Aaron J. Schueneman MD

  3. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng MD, PhD

  4. Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Joseph M. Herman MD

  5. The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elizabeth A. Sugar PhD, Jennifer Uram PhD, Elaine Bigelow BS, Joseph M. Herman MD, Barish H. Edil MD, Elizabeth M. Jaffee MD, Lei Zheng MD, PhD & Daniel A. Laheru MD

  6. The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Joseph M. Herman MD, Barish H. Edil MD, Elizabeth M. Jaffee MD, Lei Zheng MD, PhD & Daniel A. Laheru MD

  7. Departments of Biostatistics and Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Elizabeth A. Sugar PhD

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  1. Aaron J. Schueneman MD
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Corresponding author

Correspondence to Lei Zheng MD, PhD.

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Schueneman, A.J., Sugar, E.A., Uram, J. et al. Low Total Lymphocyte Count Is Associated with Poor Survival in Patients with Resected Pancreatic Adenocarcinoma Receiving a GM-CSF Secreting Pancreatic Tumor Vaccine. Ann Surg Oncol 20 (Suppl 3), 725–730 (2013). https://doi.org/10.1245/s10434-013-3262-5

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  • DOI: https://doi.org/10.1245/s10434-013-3262-5

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