Chronic myeloid leukaemia, treatment

Peggs K, Mckinnon S. Imatinb mesylate - the new gold standard for treatment of chronic myeloid leukaemia. N Engl J Med 2003 348 1048-50. 

It is indicated in acute myelocytic leukaemia, acute lymphocytic leukaemia, chronic myeloid leukaemia (blast phase), non-Hodgkin s lymphoma in children, treatment and maintenance of meningeal neoplasms, erythroleukaemia. 

Eaves CJ, Eaves AC. Progenitor cell dynamics. In Carella AM, Daley GQ, Eaves CJ eds. Chronic myeloid leukaemia biology and treatment. London Martin Dunitz 2001 73-100. 

Weisberg, E., Manley, P. W., Cowan-Jacob, S. W., Hochhaus, A., Griffin, J. D. Second Generation Inhibitors of Bcr-Abl for the Treatment of Imatinib-Resistant Chronic Myeloid Leukaemia. Nature Rev. 2007, 7, 345-357. 

Weisberg E et al (2007) Second generation inhibitors of BCR-ABL for the treatment of ima-tinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 7 345-356... 

Panobinostat (LBH-589) 79 (Novartis) is being evaluated in Phase II/III trials for the treatment of refractory cutaneous T-cell lymphoma, while Phase II/III trials against refractory chronic myeloid leukaemia have been completed.191 Panobinostat 79 is also being evaluated against a variety of other... 

Russo D, Candoni A, Zuffa E, Minisini R, Silvestri F, Fanin R, Zaja F, Marline Hi G, Tura S, Botta G, Baccarani M. Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph-f chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha. Br J Haematol 1996 94(2) 300-5. 

The sulphonoxyalkane myleran (busulfan 7) has distinct biological properties causing a particularly pronounced suppression of granulocytes. Mainly for this reason it has been traditional choice for chronic myeloid leukaemia but more recently other alkylating agents have proved to be just as effective in the treatment of this condition. 

Manley, P.W., Cowan-Jacob, S.W., and Mestan, J. (2005) Advances in the structural biology, design and clinical development of Bcr-Abl kinase inhibitors for the treatment of chronic myeloid leukaemia. Biochim. Biophys. Acta. 1754,3-13. 

The use of the other tyrosine kinase inhibitor imatinib, which blocks the enzymatic action of the BCR-ABE fusion protein, has represented a critical advance in chronic myeloid leukaemia (CML) treatment. However, a subset of patients initially fails to respond to this treatment. Use of complementary DNA (cDNA) microarray expression prohling, a set of 46 genes was differentially expressed in imatinib responders and non-responders. A six-gene prediction model was constructed, which was capable of distinguishing cytogenetic response with an accuracy of 80% [66]. 

A patient with chronic myeloid leukaemia who had responded poorly to treatment with etoposide, mitoxantrone and cytarabine for blast crisis, returned to the chronic phase when given etoposide with ciclosporin. An in vitro study by the same authors showed that etoposide was partially toxic to blast cells but that its effect on blast cells was increased sixfold when it was given with ciclosporin. ... 

A patient with chronic myeloid leukaemia developed a pustular eruption while taking imatinib 400 mg daily, increased to 800 mg daily 12 weeks after starting to take voriconazole for pulmonary aspergillosis. His imatinib plasma levels were approximately twice the predieted levels while taking both drugs. His eondition improved within 3 weeks of stopping both voriconazole and imatinib, and did not recur with voriconazole treatment alone. ... 

Ross DM. Peripheral neuropathy on imati-nib treatment for chronic myeloid leukaemia. Suspected adverse drug interaction with amlodipine. Intern Med J 2009 39 708. 

Hydroxyurea, an inhibitor of ribonucleotide reductase inhibitor, is used to treat cancers such as chronic myeloid leukaemia. However, also increases foetal haemoglobin production which may be useful in the treatment of thal-assaemias and sickle cell disease [59 ]. A meta-analysis that analysed the effects and side effects of hydroxyurea therapy on patients with beta-thalassaemia was completed this year [60 ]. The report concluded that no randomised clinical trial had been performed. It also showed that haemoglobin levels after treatment showed modest but significant increases in both transfusion-dependent and transfusion-independent patients. 

The oral preparation of this alkylating agent is widely used in the treatment of chronic myeloid leukaemia. The hazards of busulphan administration are now well recognized (see SED VIII, p. 953), the most serious being myelosuppression which may continue to progress despite the termination of busulphan therapy. Several further reports of cataract developing in patients receiving busulphan have been published recently (2, 11,32, 70). 

Use of imatinib 400 or 600 mg daily for the treatment of chronic myelogenous leukaemia was associated with improved glyeaemie eontrol in 6 of 7 diabetic patients. This allowed a reduetion in insulin dose in 2 patients and oral antidiabetic drug dosage in 4 patients. A ease report deseribes a 70-year-old woman with type 2 diabetes who needed a reduetion in her insulin dose when she was given imatinib for ehronie myeloid leukaemia. Later, while still taking imatinib, she was able to stop the insulin completely. ... 

---