Inflammatory cytokines predominate in cases of tumor regression after hematopoietic stem cell transplantation for solid cancer.

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (SCT) has recently been presented as promising immunotherapy against renal cell, colon, ovarian, breast, and primary liver cancer. Because clinical results demonstrate a variable effect on metastases, we studied whether there is an association between the clinical response and free cytokines in serum. Two patients with metastatic colorectal and 4 with renal cell cancer underwent allogeneic SCT. Conditioning included fludarabine (30 mg/m2) for 3 or 5 days, using sibling or matched unrelated donors, respectively, followed by 2 Gy total body irradiation (n=5) or cyclophosphamide (60 mg/kg) for 2 days (n=1). Antithymoglobuline (4 mg/kg) was given to patients with matched unrelated donors (n=3). Immunosuppression was cyclosporin A, combined with mycophenolate mofetil (n=5) or methotrexate (n=1). The tumor load was examined by computer tomography of the thorax and abdomen before and 3, 6, 9, and 12 months after SCT. Free cytokines in serum were analyzed using enzyme-linked immunosorbent assay. In each patient, the ratio between inflammatory (I) and anti-I cytokines was calculated. No statistical significance was found between the cytokine ratio in correlation to the tumor load according to international response evaluation criteria in solid tumors criteria. In contrast, tumor regression was found to correlate with dominating I cytokine levels in 5/7 occasions, compared with 1/12 of cases with anti-I cytokines using our local method focusing on metastases in lungs, lymph nodes, and liver (P=.01). Thus, an increased level of I cytokines possibly mirrors tumor killing induced by type 1 T-cell response. Furthermore, anti-I cytokines might inhibit cytotoxic cells from exerting the antitumor effect of allogeneic SCT.