Dana-Farber / Brigham and Women's Cancer Center

Early Vaccine Therapy Demonstrates Promise in Longer-term Control of Chronic Lymphocytic Leukemia

Catherine Wu, MD

Results from a recently published clinical trial led by investigators at Dana-Farber/Brigham and Women’s Cancer Center suggest that autologous tumor cell vaccination may be an effective strategy in advancing longterm leukemia control following reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT).

“Reduced intensity conditioning regimens in allo-HSCT have decreased toxicities and broadened the availability of this treatment to include older patients and those with comorbidities, however, many patients treated with this therapy remain at high risk for relapse,” said Principal Investigator Catherine Wu, MD, a medical oncologist in the Hematopoietic Stem Cell Transplantation Program, part of the Center for Hematologic Oncology at Dana-Farber/Brigham and Women’s Cancer Center.

Study Design and Results

The Phase I clinical trial investigated the use of whole tumor vaccination following RIC allo-HSCT to stimulate antichronic lymphocytic leukemia (CLL) responses (J Clin Invest. 2013 September 3; 123(9): 3756-3765.). The study included 22 patients with advanced CLL. Eighteen patients received up to six vaccines, initiated between days 30 and 45 after allo-HSCT. The other four patients developed acute graftversus- host disease (GVHD) after transplantation and did not receive the vaccine. Each vaccine consisted of irradiated autologous tumor cells admixed with granulocytemacrophage colony-stimulating factor (GM-CSF)-secreting bystander cells.

At a median follow-up of 2.9 years, the estimated two-year progression-free and overall survival rates of vaccinated subjects were 82 percent and 88 percent respectively. Impact of vaccination on T cell activity also was evaluated. Specific findings included:

  • Early post-transplant vaccination had a modest impact on T cell recovery;
  • Systemic tumor-specific T cell responses developed following vaccination;
  • Polyfunctional tumor-reactive T cell responses were induced following vaccination;
  • Reactivity to CLL-specific targets was induced by vaccination.

“We have discovered a possible way to extend disease control using a therapy that enhances the graft versus leukemia effect in patients with advanced CLL,” said Dr. Wu. “Our results support further study of this approach.”

Whole tumor-cell vaccination

Whole tumor-cell vaccination early after allogeneic stem cell transplantation. Subcutaneously injected irradiated autologous cancer cells provide a source of tumor antigens at the vaccination site (1). Granulocyte macrophage colony-stimulating factor (GM-CSF) secreted by irradiated bystander cells stimulates the recruitment, maturation and immunostimulatory activity of dendritic cells (DCs) at the vaccination site (2). The allograft contains hematopoietic precursor cells and mature T cells, which might be tumor-reactive, alloreactive or non-alloreactive. Early after allogeneic stem cell transplantation (allo-HSCT), homeostatic cytokines support T cell expansion in the lymphopenic host (3). Autologous whole tumor cell-based vaccination may tip the balance between leukemiaspecific and alloreactive T cell responses in favor of a graft-vs.-leukemia (GvL) effect. GvHD, graft-vs.-host disease.

 

 

 

 

 

 

 

 

 

 

 

 

 

 


About the Adult Stem Cell Transplantation Program

The Adult Stem Cell Transplantation Program at Dana-Farber/ Brigham and Women’s Cancer Center is one of the largest and most experienced in the world. The Program features 30 credentialed transplant physicians and more than 50 additional transplant experts. Since its founding in 1972, the Program has performed more than 7,000 transplants, including transplants for older adults and others with complex cases. It consistently exceeds expected outcomes set by the Center for International Blood and Marrow Transplant Research and operates an active research enterprise engaged in major multicenter trials. In addition, the Program offers specialized services in pathology, imaging, radiation oncology, and infectious disease; dedicated services for immunocompromised patients, those with graft-versus-host disease, and those with veno-occlusive disease; comprehensive support for related and unrelated transplant donors, for survivors, and for caregivers; and close collaboration with providers in the community throughout the continuum of care.

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