Modulation of acute graft-versus-host disease after allogeneic bone marrow transplantation by tumor necrosis factor α (TNFα) release in the course of pretransplant conditioning: Role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNFα (MAK 195F)

E. Holler, H. J. Kolb, J. Mittermüller, M. Kaul, G. Ledderose, Th Duell, B. Seeber, M. Schleuning, R. Hintermeier-Knabe, B. Ertl, J. Kempeni, W. Wilmanns

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192 Scopus citations

Abstract

Contribution of host-related cytokine release in the course of pretransplant conditioning to early tissue damage and induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) has been shown in experimental models. We performed a clinical phase I/II trial applying a monoclonal antibody neutralizing human tumor necrosis α (TNFα) during pretransplant conditioning as additional prophylaxis in high-risk patients admitted to allogeneic BMT; TNFα serum levels and clinical courses in 21 patients receiving anti-TNFα prophylaxis were compared with data from 22 historical controls. Absence of significant release of TNFα in the period of busulphan (BUS) treatment, but significant induction of TNFα by total body irradiation (TBI) and cyclophosphamide (CY) conditioning were correlated with significantly earlier onset of acute GVHD in patients receiving TBI/CY regimens as compared with BUS/CY-treated patients. Prophylactic application of monoclonal anti-TNFα seemed to postpone onset of acute GVHD from day 15 to day 25 (P < .05) after TBI/CY and from day 33 to day 53 after BUS/CY (P < .10) conditioning. Application of monoclonal anti-TNFα in low and intermediate doses was safe and not associated with an increased incidence of infectious or hematologic complications. Thus, our data provide indirect and direct evidence for involvement of conditioning-related cytokine release in induction of early acute GVHD in the clinical setting and support further investigation of this novel approach in randomized trials.

Original languageEnglish
Pages (from-to)890-899
Number of pages10
JournalBlood
Volume86
Issue number3
StatePublished - 1 Aug 1995
Externally publishedYes

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