Immunotherapy with interleukin-2 and alpha-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 alpha-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 10(5) IU/m2/day for 5 of 7 days each week and continued for 4 weeks. Once engraftment occurred, alpha-IFN was initiated at a dose of 1 x 10(6)/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 20000/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 degrees 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.
Meehan
K R
KR
Division of Hematology and Oncology, Georgetown University Medical Center and the Vincent T Lombardi Cancer Center, Washington, DC 20007, USA.
Arun
B
B
Gehan
E A
EA
Berberian
B
B
Sulica
V
V
Areman
E M
EM
Mazumder
A
A
Lippman
M E
ME
D000328:Adult; D001706:Biopsy; D001943:Breast Neoplasms / Q000628:therapy*; D002470:Cell Survival; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008875:Middle Aged; D012867:Skin / Q000473:pathology; D019172:Transplantation Conditioning; D016896:Treatment Outcome
D016898:Interferon-alpha; D007376:Interleukin-2