Myeloablative radioimmunotherapy with ¹⁸⁸Re-CD66mAb before stem cell transplantation

Summary

Aim: Tumour necrosis factor-α (TNF-α) serum levels may increase due to intensive conditioning regimes with highdose- chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with ¹⁸⁸Re- CD-66-mAb on changes on TNF-α serum levels. Patients, methods: In 18 patients we measured TNF-α before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-α we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Results: Compared to the basal levels before, the levels of TNF-α after conditioning with ¹⁸⁸Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 ± 6.6 pg/ml) and chemotherapy (10.8 ± 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with ¹⁸⁸Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-α. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD.

Zusammenfassung

Ziel: Die Serumspiegel von Tumornekrosefaktor-α (TNF-α) steigen durch aggressive myeloablative Konditionierungstherapien mit Hochdosis-Chemotherapie und total body irradiation (TBI) vor allogener Stammzelltransplantation. Dies ist mit einer erhöhten Rate der akuten graft versus host disease (aGvHD) assoziiert. In dieser prospektiven Studie wurde der Einfluss der myeloablativen Radioimmuntherapie mit ¹⁸⁸Re-CD-66-mAb auf Änderungen von TNF-α-Serumspiegel untersucht. Patienten, Methode: Bei 18 Patienten wurden vor und bis zu 96 Stunden nach der Radioimmuntherapie, bei 2 Patienten zusätzlich nach TBI und bei 9 Patienten nach der Hochdosis-Chemotherapie die Serumspiegel von TNF-α mittels Festphasen-Chemi - lumineszenz-Enzymimmunoassay (Immulite 1000 DPC Biermann, Bad Nauheim) bestimmt. Die mittlere Nachbeobachtungszeit zur Erfassung der aGVHD betrug 100 Tage nach Stammzelltransplantation. Ergebnisse: Gegenüber den Ausgangswerten vor Konditionierung waren die Serumspiegel von TNF-α bei 17/18 Patienten nach der myeloablativen Konditionierung mit ¹⁸⁸Re-CD-66-mAb weiterhin nicht pathologisch erhöht. Im Gegensatz dazu stiegen die initial physiologischen Serumspiegel von TNF-α 48 Stunden nach TBI auf pathologische Werte von 13,2 ± 6,6. pg/ml und 10,8 ± 15,7 pg/ml nach der Hochdosis-Chemotherapie. In unserer Studie war die aGvHD-Inzidenz mit 22,2% insgesamt niedrig (n = 4/18). Schlussfolgerung: Diese Untersuchung belegt, dass die zusätzliche Konditionierung mit ¹⁸⁸Re-CD-66-mAb nicht zu einer vermehrten Freisetzung des proinflammatorischen Zytokins TNF-α führt. Dies kann ein erster Hin - weis sein, dass zusätzliche Radioimmuntherapie kein signifikanter Faktor für eine zusätzliche konditionierungs - assoziierte aGvHD ist.

Keywords

Radioimmunotherapy - tumour necrosis factor-α - anti-CD66 - leukaemia - transplantation - aGvHD

Schlüsselwörter

Radioimmuntherapie - Tumornekrosefaktor-α - anti-CD66 - Leukamie - Transplantation - aGVHD

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