Emerging molecular technologies suggest that drugs targeting the genetic defects of leukaemic cells could revolutionise management of acute lymphoblastic leukaemia (ALL), which tends to affect young children. And the development of new drugs has helped treat chronic lymphoblastic leukaemia (CLL), although unfortunately early diagnosis of this disease does not tend to affect patient outcome and there is no way of stopping it developing in affected patients, mainly adults. The issues are discussed in two Seminars in this week's edition of The Lancet.
In the first Seminar, Professor Ching-Hon Pui, St Jude Children's Research Hospital, Memphis, TN, USA, and colleagues, look at ALL, which affects both adults and children with a peak prevalence between the ages of two and five years. The authors say: "Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-free survival while reducing the toxic side-effects of current intensive regimens."
Molecular therapies targeting the genetic defects of leukaemic cells will probably replace standard combination chemotherapy and haemopoietic stem-cell transplantation in ALL patients. However, the authors caution other strategies may also be necessary since drug therapies which target, for example, certain key enzymes in ALL development and cell proliferation and survival could be hindered by the development of drug resistance. Targeted drug-therapies can also have toxic effects on healthy tissues / systems that rely on the same signalling pathways. The authors say: "As daunting as these challenges seem, the payoff in terms of understanding the pathobiology of acute lymphoblastic leukaemia and devising novel effective treatments with few or no toxic effects could be enormous, making it our charge to bring this promise to fruition."
The authors also discuss the role of cancer stem cells in developing treatment for ALL. Current evidence suggests properties of certain human cancers could cause a resurgence of tumour unless cancerous stem cells are targeted. The authors say: "Whether important subpopulations of leukaemic cells with stem-cell properties underlie some cases of relapsed acute lymphoblastic leukaemia remains to be determined, and, therefore, they must be considered in the design of molecular therapeutics."
In the second Seminar, Professor Terry Hamblin, Royal Bournemouth Hospital, Bournemouth, UK, and Professor Guillermo Dighiero, Institut Pasteur de Montevideo, Uruguay, say that CLL, the commonest form of leukaemia in Europe and North America, has a variable course with survival ranging from months to decades, and generally affects people older than 50 years. They say: "Major progress has been made in identification of molecular and cellular markers that could predict disease progression in patients with CLL."
The authors discuss how the better understanding of the function of the B-cell receptor on the surface of CLL cells, the nature of genetic lesions, and the balance between growth and death of cancerous cells have all affected the ability to give a prognosis for and manage CLL patients. They also discuss how the elderly age of many patients makes it difficult to treat CLL in a similar manner to other leukaemias -- ie, by induction chemotherapy to induce remission followed by consolidation treatment to eliminate residual disease. They say: "Many patients live long and symptom-free lives without achieving complete remission, and most are elderly and are not candidates for more intensive treatments."
A variety of new agents -- some already in the clinic --are also discussed in this second Seminar. The authors conclude: "Available treatments generally induce remission, though nearly all patients relapse, and CLL remains an incurable disease. Advances in molecular biology have advanced our understanding of the pathophysiology of the disease and, together with development of new therapeutic agents, have made management of CLL more rational and more effective than previously. Unfortunately, we know of no way that CLL can be prevented. Early detection is practised widely, but seemingly makes no difference to the patient's eventual outcome."
For Professor Ching-Hon Pui, St Jude Children's Research Hospital, Memphis, TN, USA, please contact St Jude Public Relations T) +1 901 495 3306 E) ching-hon.pui@stjude.org / Summer.Freeman@STJUDE.ORG
Professor T J Hamblin, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK T) +44 (0) 1202 267154 E) terjoha@aol.com
PDF OF SEMINAR: http://multimedia.thelancet.com/pdf/press/Leukaemia.pdf
Journal
The Lancet