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

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 less than or equal to9.5 mukat/l, bone marrow cellularity less than or equal to70%, 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.