Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Abstract

Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph ؉ below 35%], and 4 minor [Ph ؉ , 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P ‫؍‬ .001), longer median survival (7 versus 4 months, P ‫؍‬ .04), and lower 4-week induction mortality (4% versus 15%, P ‫؍‬ .07).Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML. (Blood. 2002;99:3547-3553)

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders

“…1,2 This selective activity has translated into remarkable response efficacy in patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML). [3][4][5][6][7][8][9] Sixty percent of patients with CML who do not respond to interferon-alpha (IFN-␣) therapy achieved a major cytogenetic response with imatinib. 3,4 Significant responses have also been reported in CML pa-tients in accelerated 7,10 and blastic phases.…”

“…[3][4][5][6][7][8][9] Sixty percent of patients with CML who do not respond to interferon-alpha (IFN-␣) therapy achieved a major cytogenetic response with imatinib. 3,4 Significant responses have also been reported in CML pa-tients in accelerated 7,10 and blastic phases. 4,8,9 Therapy was well tolerated.…”

Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia

“…After making the diagnosis of CML a 3-days chemotherapy cycle with idarubicin and cytarabin was begun in order to obtain a more intense cytoreduction and then we started a therapy with imatinib. In blast crisis therapy with imatinib is less toxic and produces a higher response rate in comparison with standard cytarabine combination [9]. During treatment of patients in blast crisis with imatinib severe citopenias are frequent and represents the main reason for drug discontinuation.…”

“…During treatment of patients in blast crisis with imatinib severe citopenias are frequent and represents the main reason for drug discontinuation. Most cytopenias are probably due to the direct pharmacological effect of imatinib on leukemic cells and the poor normal bone marrow reserve in patients with blast-phase disease [9]. The time interval between the diagnosis of blastic crisis and the beginning of imatinib therapy associated with the absence of additional cytogenic abnormalities are the only significant prognostic factors for the event free survival and the overall survival of these patients [10].…”

“…The time interval between the diagnosis of blastic crisis and the beginning of imatinib therapy associated with the absence of additional cytogenic abnormalities are the only significant prognostic factors for the event free survival and the overall survival of these patients [10]. Imatinib therapy produces a high percentage of sustained hematological remission in patient with CML in blast crisis, a minority of the patients also obtain some degree of cytogenetic response [9]. These responses are transient and additional therapy should be offered [10].…”