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

• Published in: Leukemia Vol. 17; no. 9; pp. 1827 - 1833
• Main Authors: HAST, R, HELLSTRÖM-LINDBERG, E, LINDER, O, LÖFVENBERG, E, NILSSON-EHLE, H, PAUL, C, SAMUELSSON, J, TANGEN, J-M, TIDEFELT, U, TURESSON, I, WAHLIN, A, WALLVIK, J, OHM, L, WINQUIST, I, ÖBERG, G, BERNELL, P, BJÖRKHOLM, M, CELSING, F, DAHL, I-M, DYBEDAL, I, GAHRTON, G, LINDBERG, G, LERNER, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.09.2003; Nature Publishing Group
• Subjects: 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; Biological and medical sciences; Blast cells; Bone marrow; Cell Transformation, Neoplastic; Chemotherapy; Cytarabine - adverse effects; Cytarabine - therapeutic use; Cytogenetics; Daunorubicin - adverse effects; Daunorubicin - therapeutic use; Female; Follow-Up Studies; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Hematologic and hematopoietic diseases; Humans; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (granulocytic); Macrophages; Male; Medical prognosis; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - pathology; Patients; Prospective Studies; Rank tests; Refractory anemia; Regression analysis; Remission; Remission Induction; Side effects; Statistical analysis; Survival; Survival Rate; Thioguanine - adverse effects; Thioguanine - therapeutic use; Antineoplastic agent; Human; Drug combination; Prognosis; Enzyme; Acute; Cytokine; Malignant hemopathy; prognostic factors; Induction treatment; L-Lactate dehydrogenase; Myelodysplastic syndrome; S-LDH; Chemotherapy; Treatment; acute myeloid leukemia; Polypeptide; GM-CSF; myelodysplastic syndromes; Oxidoreductases; Predictive factor; Granulocyte macrophage colony stimulating factor; Acute myelocytic leukemia
• ISSN: 0887-6924; 1476-5551
• 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.