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Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF)

Therapie myelodysplastischer Syndrome mit hohem Leukämierisiko mit niedrig dosiertem Cytosin-Arabinosid und Granulozyten-Macrophagen Kolonie-stimulierendem Faktor (rhGM-CSF)

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Summary

Symptomatic patients with myelodysplastic syndromes (MDS) and 10–30% blasts in the bone marrow were treated with low-dose AraC (2×10 mg/m2 subcutaneously (sc) days 1–14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2×150 µg protein/day sc) given either subsequently (days 15–21) or simultaneously (days 8–14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17–80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.

Zusammenfassung

Symptomatische Patienten mit myelodysplastischen Syndromen und Blastenvermehrung (10–30% im Knochenmark) wurden mit niedrig dosierten Cytosin-Arabinosid (2×10 mg/m2 s. c., Tag 1–14) und rhGM-CSF (glykosyliert Sandoz/Schering-Plough, 2×150 µg Protein/Tag für sieben Tage) behandelt. Vorgesehen waren drei bis fünf derartige Kurse. In einer Zwischenanalyse waren 82 Patienten im Alter von 17–80 Jahren (mittleres Alter 64 Jahre) auswertbar. 14 Patienten kamen in eine Vollremission (17%), 11 hatten eine gute Remission (13%) und 12 eine Teilremission (15%). Bei 21 Patienten (26%) blieb die Krankheit stabil, es traten 12 toxische Todesfälle auf (15%), acht Patienten waren progredient (10%) und drei starben an ihrem Grundleiden (4%). Als wesentliche Nebenwirkungen wurden Blutungen (25%), Infektionen (23%) und rhGM-CSF-bedingtes Fieber beobachtet (21%). Die Gabe von rh GM-CSF führte nicht zu einer vermehrten Leukämie-Entwicklung und verstärkte die Cytosin-Arabinosid-bedingten Hämorrhagien nicht. Die Gesamt-Ansprechrate von 46% erscheint relativ hoch im Vergleich zu herkömmlichen Behandlungen dieser Erkrankungen.

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  1. Medizinische Klinik III, Klinikum Großhadern, Postfach 70 12 60, W-8000, München 70, Germany

    H. H. Gerhartz

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Gerhartz, H.H., Marcus, R., Delmer, A. et al. Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). Infection 20, S116–S123 (1992). https://doi.org/10.1007/BF01705030

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