The use of stem cell transplantation in breast cancer treatment soared in the early and mid 1990s but the dramatic fall that begin in 1997 as clinical trials showed it appeared to be of little benefit continues, according to new figures published in the April edition of Annals of Oncology.
Nearly 28,000 stem cell transplants were carried out for various types of solid tumours in Europe between 1991 and 2002. Breast cancer accounted for around half of the procedures (more than 13,500). Breast cancer transplants rose from 94 in 1991 to 2,629 in 1997 on the back of promising results from phase II clinical trials where transplants were combined with high-dose chemotherapy. But, as phase III trial results showed the treatment was failing to live up to earlier hopes, they dropped dramatically and the latest figures show that they were down to 330 in 2002.
The findings are from a survey carried out by an international team on behalf of the Accreditation Committee of the European Group for Blood and Marrow Transplantation (EBMT) and in co-operation with the Working Party on Solid Tumours and the Working Party on Paediatric Diseases.
Seven other specific types of solid tumours – germ cell cancer (12%), neuroblastoma (9%), Ewing's sarcoma (7%), soft tissue sarcoma (4%), ovarian cancer (3%) glioma (2%) and lung cancer (1%), plus 'others' (13%) – made up the transplant total. Ninety-eight per cent of the transplants were autologous (from the patient's own bone marrow) and two per cent were allogenic (from donors).
Lead author Professor Alois Gratwohl from the Department of Internal Medicine at Kantonsspital Basel in Switzerland, said: "In the early and mid-1990s impressive data from phase II trials as well as from registries accelerated the growth in the number of autotransplants for breast cancer. When the first results from phase III studies become available a wave of pessimism began to appear and the numbers undergoing high-dose chemotherapy began to drop. Most recent results remain ambiguous and the value of stem cell transplant in breast cancer still needs to be determined in selected categories. But, it might be an effective tool in treating some subsets of patients. What is encouraging is that the fall in the numbers of stem cell transplants illustrates that doctors have been quick to react to the negative findings in the trials and to share that information."
He said that the move towards stem cell transplants in a range of solid tumours had been triggered by preliminary positive retrospective and prospective data. However, attitudes changed following doubts on initial reports, the failure of prospective studies to find an advantage in breast cancer and a growing awareness of the need for evidence.
In an editorial commenting on the survey Dr Richard Childs, senior investigator at the National Heart, Lung and Blood Institute at NIH in Bethesda, Maryland, said: "The transplant trends presented here and elsewhere provide direct insight into the level of enthusiasm of physicians and patients alike for stem cell transplants in specific diseases. In contrast to haematological malignancies, such as relapsed lymphoma and multiple myeloma where survival can be prolonged, data supporting a beneficial role for autologous transplants in most solid tumours are lacking."
The survey identified different trends over time for autologous transplants in different cancers – a continuing steady increase in transplant use in neuroblastoma and Ewing's sarcoma, a stable situation in glioma, soft tissue sarcoma and germ cell tumours and an increase followed by a decrease in breast, lung and ovarian cancer. For allogenic transplants, figures remained low generally except in the 'other' disease category where there has been a marked increase in the last three years of the period, primarily due to renal cell carcinoma where there were 80 transplants in 2002. There has also been an increase in breast and lung cancers although numbers remain small.
Transplant rates overall differed markedly between European countries, varying from zero in several countries to more than 400 per 10 million of the population in others.
Professor Gratwohl said that comprehensive surveys such as that of the EBMT reached over 95% of activity in the field. Although prospective studies were needed to provide evidence of the end results of transplants, the survey on current practice enabled differences in opinions between transplant specialists to be quantified. "Data in 2002 suggest that there is consensus in Europe on autologous transplants in Ewing's sarcoma and near consensus on neuroblastoma and germ cell cancer. It reflects current practice, gives information on consensus or dissension and provides an objective basis for patient counselling and health-care planning."
Commenting on the findings that, in contrast to the fall in autologous transplants, allogenic transplants for metastatic tumours were rising – up from 15 in 1997 to 159 in 2002 – Dr Childs said that it was now known that allogenic transplantation induced a curative graft versus host effect in patients with a variety of blood cancers. This had shifted specialists' perception of the factors that contributed to cure – downplaying the role of intensified doses and highlighting the power of the graft versus tumour effect. This shift was now being seen in solid tumour treatment with small studies testing whether inducing graft versus host effect in solid chemotherapy resistant metastatic tumours would produce a similar benefit.
However he urged caution. "Although these pilot studies in solid tumours have been invaluable as they have provided important proof of the concept that graft versus host may have potential, it is critical that we don't repeat the mistake that has occurred with autologous transplants in breast cancer – a premature rush to conduct large numbers of transplants based on an overly optimistic assumption of efficacy fuelled by limited clinical data. It is important to temper enthusiasm until the advantages and pitfalls become clear."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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