Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL

Abstract

Chronic myeloid leukaemia (CML) is a malignant disease of the bone marrow characterised by the presence of the Philadelphia (Ph) chromosome. About 20% of acute lymphoblastic leukaemia (ALL) patients also show this genetic abnormality. A new drug, imatinib (Glivec s , Novartis Pharma AG, Basel, Switzerland, and formerly STI571) is having a profound effect on the treatment and management of all stages of CML and Philadelphia chromosome positive (Ph+) ALL. New treatment algorithms are being developed. Should imatinib replace or be combined with existing therapies? To address this question, we review the pros and cons of therapy with interferon-a (IFN-a), allogeneic transplantation, autologous transplantation, imatinib, and in the case of Ph+ ALL, chemotherapy and experimental approaches. Conservative and aggressive treatments will be discussed and new molecular methods of monitoring cytogenetic response and their significance will also be reviewed.

Visual disturbance due to retinal edema as a complication of imatinib

“…Recent studies revealed that this agent also inhibits kinases other than ABL, such as platelet-derived growth factor receptor (PDGFR) and KIT, and that it is effective for a variety of hematologic and nonhematologic malignancies. 1 A variety of adverse events including cytopenia, nausea, vomiting, edema, myalgia, diarrhea, rash, fatigue, and anorexia have been reported in the context of phase I-III trials in chronic myelocytic leukemia (CML) and phase II trials in gastrointestinal stromal tumors (GIST), 2 while most patients tolerate it at clinically effective doses. Herein, we describe a patient with CML who developed severe ocular complication during treatment with imatinib.…”

Dasatinib and nilotinib for imatinib-resistant or -intolerant chronic myeloid leukaemia: a systematic review and economic evaluation.

“…30 Acute leukaemia-type chemotherapy Once people develop a myeloid or lymphoid blastic transformation, acute leukaemia-type chemotherapy can be used as a debulking or cytoreductive treatment prior to treatment with other agents including SCT; this therapy generally produces a HR in the region of 40%. 55 …”

Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms

“…1 The Bcr/Abl kinase signals to a variety of downstream survival pathways, including the mitogenactivated protein kinase kinase (MEK)/extracellular signalregulating kinase (ERK) cascade, Akt, signal transducers and activators of transcription (STATs), and nuclear factor B (NF-B), among others. [2][3][4] Activation of these pathways in Bcr/Abl ϩ cells results in increased expression of several antiapoptotic proteins, such as Bcl-xL.…”