[show abstract][hide abstract] ABSTRACT: The choice of primary treatment for patients with chronic myeloid leukemia (CML) diagnosed in chronic phase has become exceedingly difficult. There is little doubt that allogeneic stem cell transplantation can eradicate the leukemia and that a graft-versus-leukemia effect makes a major contribution to this result; conversely, only a minority of patients are eligible for transplantation, which still carries an appreciable risk for death or protracted illness. For most patients, interferon-alpha (IFN-alpha) prolongs life to some degree in comparison with hydroxyurea, but it is associated with considerable toxicity. The newly introduced tyrosine kinase inhibitor STI571 induces complete hematologic remission in almost all patients and is associated with a very high rate of cytogenetic response; its capacity to prolong life in comparison with IFN-alpha is not yet established. Here are reviewed some factors that predict survival after nontransplantation therapy and after allografting for CML in chronic phase. Two contrasting options are considered for managing the patient with newly diagnosed disease, and it can be concluded that, for now, allogeneic stem cell transplantation soon after diagnosis should continue to be offered as an option for selected patients. Further experience with the use of STI571 as a single agent or in combination with other antileukemic agents may alter the picture in the near future.
[show abstract][hide abstract] ABSTRACT: Interferon-alpha (IFN-alpha) has significantly prolonged survival in chronic myeloid leukemia (CML), but some patients do not respond and many responses are not durable. To improve the results, IFN-alpha has been combined with other treatments, but so far only the association with low-dose arabinosyl cytosine (LDAC) has been shown to increase the response rate and to prolong survival. Here are reported the results of a study of 538 Philadelphia chromosome-positive CML patients who were assigned at random to treatment with IFN-alpha 2a alone or in combination with LDAC. The scheduled dose of IFN-alpha 2a was 5(6) IU/m(2)/d. The scheduled dose of AC was 40 mg/d for the first 10 days of each month of treatment. The efficacy endpoints were a complete hematologic response rate at 6 months (62% in the IFN-alpha-plus-LDAC arm versus 55% in the IFN-alpha arm; P =.11), major cytogenetic response (MCgR) rate at 24 months (28% versus 18%; P =.003), and overall survival (5-year survival, 68% versus 65%; P =.77). Treatment did not affect overall survival within different prognostic risk groups: low, intermediate, or high. Also the duration of MCgR was identical. The results of this study confirm the results of a similar French study only for the response rate, not for survival, suggesting that the relationship between cytogenetic response and survival may be extremely variable and that a meta-analysis of these and other studies of IFN-alpha versus IFN-alpha plus LDAC is required to settle the issue of the role of LDAC in the treatment of CML.
[show abstract][hide abstract] ABSTRACT: Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine.
Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months.
The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P<0.001).
The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.
New England Journal of Medicine 01/1997; 337(4):223-229. · 51.66 Impact Factor
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