[Therapy of Philadelphia chromosome positive acute lymphatic leukemia (Ph+ ALL) with an inhibitor of abl-tyrosine kinase (Glivec)].
BACKGROUND
Ph+/bcr-abl positive ALL has the worst prognosis of all subgroups of ALL; only a small minority of patients are cured with currently established treatment regimens. The central pathogenetic role of the constitutively activated and deregulated abl-tyrosine kinase that is a direct consequence of the bcr-abl rearrangement opens the possibility of treating this disease using a molecularly targeted approach. The recent development of the selective abl-tyrosine kinase inhibitor Glivec (formerly STI571) opens the opportunity of blocking the signal transduction pathways critically involved in bcr-abl induced leukemogenesis.
Glivec exerts a significant anti-leukemic effect in patients with Ph+ ALL, with a remarkably favorable toxicity profile. This enables transfer of a subset of the responding patients to a potentially curative allogeneic stem cell transplantation. Despite promising initial therapeutic effects, treatment with Glivec alone is not able to achieve cures in the majority of patients with relapsed or refractory Ph+ ALL. The earlier administration of Glivec in patients with "de novo" ALL as well as combining it with other treatment modalities is likely to improve treatment results. The identification of specific resistance mechanisms towards Glivec should provide valuable information regarding the development of clinical strategies to circumvent resistance. Glivec can already be considered an important element in the treatment of Ph+ ALL, although the most effective ways of employing this novel agent remain to be established.
Ottmann
Oliver G
OG
Abteilung Hämatologie/Onkologie, Medizinische Klinik III der Johann-Wolfgang-Goethe-Universität Frankfurt/Main. ottmann@em.uni-frankfurt.de
Wassmann
Barbara
B
Hoelzer
Dieter
D
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate