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No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease

Leukemia volume 17, pages 1827–1833 (2003)Cite this article

Abstract

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte–macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels ⩽9.5 μkat/l, bone marrow cellularity ⩽70%, and WBC counts <4.0 × 109/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.

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Acknowledgements

This work was supported by grants from the Cancer Society in Stockholm, the Swedish Cancer Society, Karolinska Institutet Funds, and by an unrestricted grant from Schering-Plough AB, Stockholm, Sweden.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden

    R Hast, L Ohm & P Bernell

  2. Department of Hematology, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden

    E Hellström-Lindberg

  3. The Leukemia Group of Middle Sweden (LGMS), Sweden

    R Hast, M Björkholm, F Celsing, G Gahrton, C Paul, J Samuelsson, U Tidefelt, G Öberg & P Bernell

  4. The Nordic MDS Group, Sweden, Norway

    E Hellström-Lindberg, I-M Dahl, I Dybedal, G Lindberg, R Lerner, O Linder, E Löfvenberg, H Nilsson-Ehle, J-M Tangen, I Turesson, A Wahlin, J Wallvik & I Winquist

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Hast, R., Hellström-Lindberg, E., Ohm, L. et al. No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease. Leukemia 17, 1827–1833 (2003). https://doi.org/10.1038/sj.leu.2403035

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