Cancer Res Treat.  2012 Jun;44(2):133-141.

Irradiation of Donor Mononuclear Cells for Treatment of Chemorefractory Metastatic Solid Cancers: A Community-Based Immune Transplant Pilot Study

• Reynolds J
• Watkins JM
• Dufan TA
• Kubsad SS

Abstract

PURPOSE
Chemotherapy has demonstrated ability to generate tumor antigens secondary to induction of apoptosis, against which human leukocyte antigen-compatible, irradiated, related donor mononuclear cells may be administered with immune stimulation to activate antigen presenting and cytotoxic T cells, while minimizing risk of graft-versus-host disease (GVHD). The present study endeavours to describe feasibility and efficacy of this treatment, specifically in the community setting.
MATERIALS AND METHODS
Eligible patients had rapidly progressive, chemorefractory metastatic solid tumors. Treatment consisted of intravenous etoposide and cyclosporine for three days followed by granulocyte-macrophage colony-stimulating factor for 5 days. The following week, 5x10(7) haploidentical or more closely matched irradiated donor mononuclear cells were given weekly for 10 weeks along with interleukin-2.
RESULTS
Three patients were enrolled, and the regimen was well-tolerated, with no GVHD observed. All patients had clinical response, despite advanced and heavily pretreated disease.
CONCLUSION
The above-outlined protocol demonstrates favorable tolerability and efficacy, and appears to be feasible in the community setting. While the optimal chemotherapy, immunostimulation, and irradiation regimens may be further optimized, future investigation appears warranted, and may include community oncology programs.

Keyword

Residual neoplasm; Mononuclear leukocytes; Immunomodulation

MeSH Terms

Antigens, Neoplasm
Apoptosis
Cyclosporine
Etoposide
Graft vs Host Disease
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Immunization
Immunomodulation
Leukocytes
Leukocytes, Mononuclear
Neoplasm, Residual
Pilot Projects
T-Lymphocytes
Tissue Donors
Transplants
Antigens, Neoplasm
Cyclosporine
Etoposide
Granulocyte-Macrophage Colony-Stimulating Factor

Figure

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  Fig. 1 Schema for the first two patients on the immune transplant protocol before changes were made for the third patient. PD, progressive disease; PR, partial response; SD, stable disease; MR, mixed response; CR, complete response; IL-2, interleukin-2.

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  Fig. 2 Graph of tumor marker carcinoembryonic antigen (CEA) vs. time, the immune transplant is given during the curved arrow.

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  Fig. 3 Patient 2 performance status vs. donor transfusion time (by specific donor). The arrow designates the time of the accident.

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  Fig. 4 A typical skin reaction at the interleukin-2 injection site for those patients receiving haploidentical mononuclear cells.

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  Fig. 5 Patient 3 performance status vs. donor transfusion time (by specific donor).

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