TY - JOUR
T1 - Randomized comparison of interferon α and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II)
T2 - Prolongation of survival by the combination of interferon α and hydroxyurea
AU - Hehlmann, R.
AU - Berger, U.
AU - Pfirrmann, M.
AU - Hochhaus, A.
AU - Metzgeroth, G.
AU - Maywald, O.
AU - Hasford, J.
AU - Reiter, A.
AU - Hossfeld, D. K.
AU - Kolb, H. J.
AU - Löffler, H.
AU - Pralle, H.
AU - Queißer, W.
AU - Griesshammer, M.
AU - Nerl, C.
AU - Kuse, R.
AU - Tobler, A.
AU - Eimermacher, H.
AU - Tichelli, A.
AU - Aul, C.
AU - Wilhelm, M.
AU - Fischer, J. T.
AU - Perker, M.
AU - Scheid, C.
AU - Schenk, M.
AU - Weiß, J.
AU - Meier, C. R.
AU - Kremers, S.
AU - Labedzki, L.
AU - Schmeiser, T.
AU - Lohrmann, H. P.
AU - Heimpel, H.
N1 - Funding Information:
The assistance of M Dumke, C Folz, G Lalla, K Adam, and K Enghofer is greatfully acknowledged. This study was supported by the Süddeutsche Hämoblastosegruppe (SHG) through a grant of Hoffmann-La Roche to SHG and by the Forschungsfond of the Fakultät für Klinische Medizin Mannheim, University of Heidelberg.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - The optimum treatment conditions of interferon (IFN) α therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n = 194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n = 21), major in 14% (n = 24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.
AB - The optimum treatment conditions of interferon (IFN) α therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n = 194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n = 21), major in 14% (n = 24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.
KW - Chronic myeloid leukemia
KW - Duration of chronic phase
KW - Hydroxyurea
KW - Interferon α
KW - Survival
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U2 - 10.1038/sj.leu.2403006
DO - 10.1038/sj.leu.2403006
M3 - Article
C2 - 12886239
AN - SCOPUS:0038483374
SN - 0887-6924
VL - 17
SP - 1529
EP - 1537
JO - Leukemia
JF - Leukemia
IS - 8
ER -