Randomized comparison of interferon α and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon α and hydroxyurea
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)...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 July 2003
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| In: |
Leukemia
Year: 2003, Volume: 17, Issue: 8, Pages: 1529-1537 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/sj.leu.2403006 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.leu.2403006 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/2403006 
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| Author Notes: | R. Hehlmann, U. Berger, M. Pfirrmann, A. Hochhaus, G. Metzgeroth, O. Maywald, J. Hasford, A. Reiter, D.K. Hossfeld, H.-J. Kolb, H. Löffler, H. Pralle, W. Queißer, M. Griesshammer, C. Nerl, R. Kuse, A. Tobler, H. Eimermacher, A. Tichelli, C. Aul, M. Wilhelm, J.T. Fischer, M. Perker, C. Scheid, M. Schenk, J. Weiß, C.R. Meier, S. Kremers, L. Labedzki, T. Schmeiser, H.-P. Lohrmann, H. Heimpel and the German CML-Study Group |
| Summary: | 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. |
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| Item Description: | Gesehen am 13.05.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/sj.leu.2403006 |