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Randomized comparison of interferon-alpha with busulfan and hydroxyurea in
chronic myelogenous leukemia. The German CML Study Group [see comments]
R Hehlmann, H Heimpel, J Hasford, HJ Kolb, H Pralle, DK Hossfeld, W Queisser, H Loffler, A Hochhaus and B Heinze
Medizinische Klinik III, Universitat Heidelberg, Mannheim, Germany.
As curative bone marrow transplantation is available only to a minority of
patients with chronic myelogenous leukemia (CML), drug therapy remains of
central interest. Several nonrandomized studies have suggested that
interferon-alpha (IFN) may prolong survival in CML. In a randomized
multicenter study the influence of IFN versus busulfan or hydroxyurea (HU)
on survival of Philadelphia-positive (Ph+) CML was examined. A total of 513
Ph+ patients were randomized for treatment as follows: 133 for IFN, 186 for
busulfan, and 194 for HU. IFN-treated CML patients have a significant
survival advantage over busulfan-treated (P = .008), but not over
HU-treated patients (P = .44). The longer survival is due to slower
progression to blast crisis. Median survival of IFN-treated patients is 5.5
years [5-year survival, 59%; 95% confidence interval (CI), 48%-70%], of
busulfan-treated patients, 3.8 years (5-year survival, 32%; CI, 24%-40%),
and of HU-treated patients, 4.7 years (5-year survival, 44%; CI, 36%-53%).
Patients who continue on IFN survive longer than those in whom IFN is
discontinued before blast crisis (P = .007). Complete hematologic
IFN-responders have a survival advantage over partial responders or
nonresponders (P = .02). Cytogenetic IFN-responders have no significant
survival advantage over nonresponders (P = .2). Patients who attain white
blood cell (WBC) counts of 10 x 10(9)/L or less have a survival advantage
in the IFN (P = .007) and HU (P = .05) groups. Whereas toxicity in the IFN
group was considerably higher than in the busulfan or HU groups,
long-lasting cytopenias necessitating discontinuation of therapy as
observed with busulfan have not been seen with IFN or HU. The problems of
conventional prognostic scores (Sokal's score, Score 1) that we observed in
IFN-treated patients support the idea that IFN changes the natural course
of CML. We conclude that, with regard to survival of CML in the chronic
phase, IFN is superior to busulfan and as effective as HU. Whether and to
what extent IFN is superior to HU appears to depend, at least in part, on
the degree of WBC suppression by HU-therapy and on the risk profile of the
patients.
Volume 84,
Issue 12,
pp. 4064-4077,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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