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

Leukemia. 2003 Sep;17(9):1827-33. doi: 10.1038/sj.leu.2403035.


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 microkat/l, bone marrow cellularity </=70%, and WBC counts <4.0 x 10(9)/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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Refractory, with Excess of Blasts / drug therapy
  • Anemia, Refractory, with Excess of Blasts / pathology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Transformation, Neoplastic
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use*
  • Daunorubicin / adverse effects
  • Daunorubicin / therapeutic use*
  • Female
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / pathology
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / pathology
  • Prospective Studies
  • Remission Induction
  • Survival Rate
  • Thioguanine / adverse effects
  • Thioguanine / therapeutic use*


  • Cytarabine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Thioguanine
  • Daunorubicin

Supplementary concepts

  • DAT protocol 1