Hast R, Hellström-Lindberg E, Ohm L, Björkholm M, Celsing F, Dahl I-M, Dybedal I, Gahrton G, Lindberg G, Lerner R, Linder O, Löfvenberg E, Nilsson-Ehle H, Paul C, Samuelsson J, Tangen J-M, Tidefelt U, Turesson I, Wahlin A, Wallvik J, Winquist I, Oberg G, Bernell P
Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
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.
