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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 23; no. 7; pp. 667 - 673
• Main Authors: MEEHAN, K. R, ARUN, B, GEHAN, E. A, BERBERIAN, B, SULICA, V, AREMAN, E. M, MAZUMDER, A, LIPPMAN, M. E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-04-1999
• Subjects: Adult; Antineoplastic agents; Autografts; Biocompatibility; Biological and medical sciences; Biopsy; Breast cancer; Breast Neoplasms - therapy; Carboplatin; Cell Survival; Chemotherapy; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Cyclophosphamide; Feasibility; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - pathology; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Immunotherapy; Interferon; Interferon-alpha - therapeutic use; Interleukin 2; Interleukin-2 - therapeutic use; Interleukins; Medical sciences; Middle Aged; Nausea; Neutropenia; Peripheral blood; Pharmacology. Drug treatments; Platelets; Skin; Skin - pathology; Stem cell transplantation; Stem cells; Toxicity; Transplantation; Transplantation Conditioning; Transplants & implants; Treatment Outcome; α-Interferon; Human; Immunopathology; Drug combination; Toxicity; Stem cell; Cytokine; Hematopoietic cell; Graft versus host reaction; Activation; Malignant tumor; In vitro; Blood; Mammary gland diseases; Autograft; Interleukin 2; Immunotherapy; Engraftment; Complication; Graft; Combined treatment; Mammary gland; Gamma interferon
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1701632

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.