Immunotherapy with interleukin-2 and α-interferon after IL-2-activated hematopoietic stem cell transplantation for breast cancer

We previously demonstrated findings suggestive of autologous GVHD in patients receiving IL-2-activated peripheral blood stem cells (PBSC) with IL-2 after transplantation. A pilot study was designed to test tolerability, feasibility and frequency of autologous GVHD and engraftment using IL-2 and α-IFN post-transplantation. After cyclophosphamide (6 g/m²) and carboplatin (1800 mg/m²), patients with high-risk stage II or III breast cancer received chemotherapy and rhG-CSF mobilized autologous PBSC that had been cultured in IL-2 for 24 h. Subcutaneous administration of IL-2 began on day 0 at 6 x 10⁵ IU/m²/day for 5 of 7 days each week and continued for 4 weeks. Once engraftment occurred, α-IFN was initiated at a dose of 1 x 10⁶/m²/day subcutaneously for 30 days. Thirty-four consecutive patients with stage II (n = 20), IIIA (n = 6) and IIIB (n = 8) disease were treated. All patients were without evidence of disease at the time of transplantation. The average time required for the ANC to reach 500/mm³ was 10 days (range: 8-11 days) and for platelets to reach 20,000/mm³ was 10.7 days (range: 6-21 days). Forty-seven percent of patients (n = 16) completed the full course of immunotherapy; the remaining patients received attenuated doses due to patient's request (n = 6), development of temperature > 38°C (n = 3), development of neutropenia (n = 3), serious infection (n = 1) and miscellaneous reasons (n = 5). Four patients experienced transient moderate toxicities (level 3) including elevated liver function tests, nausea, rash and capillary leak syndrome. Pathological findings suggestive of skin GVHD developed in 43% of patients (12/28 patients) when skin biopsies were evaluated in a blinded fashion. At 13 months post-transplant (median; range: 5-24 months), 28 patients (82%) remain disease-free. These results demonstrate the feasibility and toxicity of this regimen along with pathological findings compatible with autologous GVHD of the skin.