Imatinib (Glivec®) in the treatment of patients withaccelerated phase of chronic myelogenous leukaemia and Ph-positive acute lymphoblasticleukaemia

Overview

Five women and one man at age of 44 to 70 with relapsed or refractory Ph-positive ALL were treatedwithin multicentre study of extended access CZSTI5710114 with imatinib (Glivec®, STI 571) at the dose600mg daily. 3 patients achieved complete and 2 partial haematologic response with median durationof 157 days. The death was caused by relapse of disease despite continuing treatment with imatinib infour of five patients who died. The patient who was treated because of relapse after allogeneic stem celltransplantation achieved molecular genetic remission. In addition, 18 men and 14 women with acceleratedphase of CML at age 18 to 72 years were treated with the same dose of imatinib. Patients werefollowed-up for 454 days in median (41–597). Haematologic response (complete in 11 (34 %) and partialin 18 (56 %) patients) was achieved in median of 28 days. In 3 (9 %) patients reinstitution of chronicphase of disease was achieved only. 23 patients were assessed for cytogenetic response – 13 (57 %)achieved major (8 of them complete) response. Imatinib at dose of 600 mg daily has lead to hematologictoxicity of 3rd and 4th grade according NCI/NIH scale in three quarters of patients that causedinterruption of therapy in 19 and reduction of dose in 18 patients. Non-haematologic toxicity was notserious and was easily managed with symptomatic therapy. Progression occurred in 9 (28 %) patientsand 10 (31 %) patients died during the follow-up. The statistic analysis has confirmed that the probability of achievement of haematologic remission together with the risk of disease progression couldbe connected with parameters associated with tumour load at the beginning of treatment – WBC,splenomegaly and presence of blasts in peripheral blood. The probability of achievement of significantcytogenetic response was significantly higher in younger patients with shorter duration of CML andwith lower initial platelet count. The probability of overall survival of patients was significantlyinfluenced by the achievement of hematologic and cytogenetic remission. At present time, imatinibrepresents the most powerful drug for conservative therapy of CML. Our experience confirms its highresponse rate also in patients with accelerated phase of CML. Efficacy of imatinib treatment has beenincreased with shorter duration and less advanced disease.

Key words:
chronic myelogenous leukaemia, acute lymphoblastic leukaemia, imatinib, Glivec, STI 571,Ph chromosome, BCR/ABL, tyrosine kinase