Treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia with imatinib in combination with chemotherapy.
The presence of the Philadelphia chromosome (Ph) is associated with a very poor prognosis in acute lymphoblastic leukemia (ALL). Although hematologic complete remission (CR) is achieved in 50% to 80% of adult patients by intensive chemotherapy in multicenter studies, long-term outcome is dismal, with overall survival of approximately 10%. Currently, allogeneic hematopoietic stem cell transplantation (allo-SCT) is thought to be the only curative therapeutic modality for this leukemia in adults, but the long-term survival rates are about 40% or less, far from satisfactory. Imatinib mesylate, a recently introduced specific tyrosine kinase inhibitor of BCR-ABL, in combination with chemotherapy, resulted in more than 90% hematologic CR in adult Ph-positive ALL, including molecular CR in more than 50% of patients. The higher CR rate and less frequent relapse gave more patients a chance to receive SCT. Patients who did not qualify for allo-SCT because of the lack of a suitable donor, advanced age, or underlying medical conditions apparently showed better survival than historical control patients treated with chemotherapy alone. Although longer follow-up is required to determine the effect on survival, imatinib in combination with chemotherapy clearly has a major potential to improve the treatment of Ph-positive ALL and may cure a substantial proportion of patients without SCT.
Ohno
Ryuzo
R
Aichi Cancer Center and Aichi Syukutoku University, Chikusaku, Nagoya, Japan. ohnoryu@aichi-cc.jp
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000601:surgery; D008727:Methotrexate / Q000008:administration & dosage; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D010879:Piperazines / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D012074:Remission Induction; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide; D011239:Prednisolone; D016044:Fusion Proteins, bcr-abl; D008727:Methotrexate; D003630:Daunorubicin