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document
Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia ( CML-study II ) : prolongation of survival by the combination of interferon alpha and hydroxyurea . The optimum treatment conditions of interferon ( IFN ) alpha 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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Intervention_Pharmacological
interferon alpha and hydroxyurea
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Intervention_Pharmacological
interferon ( IFN ) alpha therapy
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Intervention_Pharmacological
hydroxyurea ( HU )
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Intervention_Pharmacological
IFN therapy
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Intervention_Pharmacological
compare the combination of IFN
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Intervention_Physical
and
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Intervention_Pharmacological
HU
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Intervention_Pharmacological
HU monotherapy
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Outcome_Physical
Complete hematologic response rates
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Outcome_Physical
cytogenetic response
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Outcome_Physical
Duration of chronic phase
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Outcome_Mortality
Median survival
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Participant_Sample-size
376
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Participant_Condition
newly diagnosed CML in chronic phase
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Participant_Sample-size
340
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Participant_Condition
Ph/BCR-ABL
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Participant_Sample-size
534 patients
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Participant_Sample-size
226 patients with IFN/HU
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Participant_Sample-size
308 patients with HU
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Participant_Sample-size
534