Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients

Bone Marrow Transplant. 1995 May;15(5):669-77.

Abstract

We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Acute Disease
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Bone Marrow Transplantation* / immunology
  • CD2 Antigens / immunology*
  • Child
  • Cytokines / blood
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / immunology
  • Humans
  • Interleukin-2 / immunology*
  • Male
  • Middle Aged
  • Pilot Projects
  • Recombinant Proteins / immunology
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • CD2 Antigens
  • Cytokines
  • Interleukin-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha