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Protocols promise head start for patients with brain tumours
SCIENCE AND MEDICINE
Protocols promise head start for patients with brain tumours “the neuropsychological follow up fitweeks for 5 cycles, the patients were ted a standard bell-shape curve”. given conventional chemotherapy of Finlay adds that he has vincristine, cisplatin, “never seen infants with cyclophosphamide, and brain tumours leading etoposide at slightly such normal lives”. higher than usual doses. As well as treating After the first cycle, more patients with the bone marrow was head-start protocol, the harvested and stored. group is also starting Then, after a sixth and a cost-analysis study. final consolidation cycle However, Finlay is of chemotherapy, the already expressing conbone marrow was fidence that the treatre-infused to replace ment will be far cheaper destroyed stem cells. than current protocols. The greatest benefit Less therapy means more Another promising of the new regimen was regimen has emerged from the same seen in neuropsychological testing. group to treat patients with recurrent Standard protocols that include medulloblastoma. The treatment radiotherapy can significantly impair involves high doses of carboplatin, mental development when used to thiotepa, and etoposide plus autolotreat young children. For patients gous stem-cell rescue. With standard receiving the head-start protocol, treatments, the survival rate for Genes harnessed in battle against chemotherapy side-effects patients with recurrent medulloblasA new gene-therapy technique to combat adverse effects of high-dose toma is very low. In the 23 patients chemotherapy has been found to be safe in a phase I clinical trial. The treated with the new regimen, the technique involves harvesting haemopoietic stem cells and treating one-third of investigators report a 35–45% eventthose cells with a retrovirus that contains the DNA for the multiple-drugfree and overall survival at 36 months resistance gene (MDR). The cells are then re-infused into the patient, as part of post-treatment. These results are an autologous stem-cell transplant. The presence of MDR makes the stem cells encouraging for future treatment resistant to the chemotherapeutic agents used to combat the cancer. The trial and long-term survival for patients findings show that the technique is safe. But, only two of the five patients with recurrent medulloblastoma, treated showed evidence of the exogenous MDR gene in their bone marrow up say the authors.
ew regimens of intensive chemotherapy and bonemarrow rescue may be beneficial for certain malignant brain tumours, according to two studies reported in the Journal of Clinical Oncology (1998; 16: 210–21; 222–28). The first regimen, aimed at newly diagnosed brain malignancies in young children, lasts only 6 months, compared with the usual treatment time of 1–2 years. This “head-start protocol” seems to increase overall survival and event-free survival rates, compared with known rates for standard protocols. An added benefit is that the new regimen does not include radiation to the brain. A team led by Jonathan Finlay (New York University Medical Center, NY, USA) treated 62 children, all under the age of 6, with malignant brain tumours. Every 3
SPL
N
to 10 weeks after transplantation. Larger efficacy trials are needed. Hannah Wunsch
Dilated cardiomyopathy carries risk for relatives
R
elatives of people with dilated cardiomyopathy are themselves highly likely to develop heart failure, according to a new study. Investigators in London, UK, studied 408 symptom-free relatives of 110 patients with dilated cardiomyopathy. 29% of relatives had an abnormal echocardiogram, with left-ventricular enlargement (LVE) being the most common abnormality. During more than 3 years of follow up, 27% of relatives with LVE developed dilated cardiomyopathy. These results suggest that the degree to which dilated cardiomyopathy is a familial disease has been seriously underestimated (J Am Coll Cardiol 1998; 31: 195–201). “In the past, we’ve only been able to identify people with dilated cardiomyopathy when they turn up with the signs of heart failure, such as breathlessness, palpitations, or fainting episodes”, said Kamran Baig (St George’s Hospital Medical
116
School, London, UK). “Although we’ve thought for some time that dilated cardiomyopathy runs in families, it’s been difficult to assimilate this knowledge into clinical practice.” It remains unclear, however, exactly how clinical practice should change. “What we don’t know just yet is whether or not any early intervention will be beneficial”, said Baig. “Our present policy after we identify people with LVE is to follow them on a yearly basis with non-invasive tests, looking for any indication of a change for the worse in their hearts. When we spot someone who is deteriorating, we start them on what we think is appropriate therapy, most often ACE [angiotensin-convertingenzyme] inhibitors, which have been shown to be effective in the early stages of heart failure.”
News in brief T-cell key in type 1 diabetes Patients with type 1 diabetes (IDDM) have T cells predisposed to attack their own pancreatic cells. But, progression to diabetes also involves a specific T-cell subset— the loss of these cells’ ability to secrete interleukin 4 correlates with IDDM (Nature 1998; 391: 177–81). Neurodegeneration unravels The abnormal protein deposits seen in non-familial Alzheimer’s disease and Down’s syndrome contain aberrant forms of ubiquitin- and amyloid precursor protein. But the abnormal proteins are likely to result not from mutations in the encoding DNA but from “frameshift” mutations in the RNA transcripts (Science 1998; 279: 242–47). The authors suggest that transcriptional mutation “may underlie a number of neurodegenerative pathologies”.
Larry Husten
THE LANCET • Vol 351 • January 10, 1998
Protocols promise head start for patients with brain tumours “the neuropsychological follow up fitweeks for 5 cycles, the patients were ted a standard bell-shape curve”. given conventional chemotherapy of Finlay adds that he has vincristine, cisplatin, “never seen infants with cyclophosphamide, and brain tumours leading etoposide at slightly such normal lives”. higher than usual doses. As well as treating After the first cycle, more patients with the bone marrow was head-start protocol, the harvested and stored. group is also starting Then, after a sixth and a cost-analysis study. final consolidation cycle However, Finlay is of chemotherapy, the already expressing conbone marrow was fidence that the treatre-infused to replace ment will be far cheaper destroyed stem cells. than current protocols. The greatest benefit Less therapy means more Another promising of the new regimen was regimen has emerged from the same seen in neuropsychological testing. group to treat patients with recurrent Standard protocols that include medulloblastoma. The treatment radiotherapy can significantly impair involves high doses of carboplatin, mental development when used to thiotepa, and etoposide plus autolotreat young children. For patients gous stem-cell rescue. With standard receiving the head-start protocol, treatments, the survival rate for Genes harnessed in battle against chemotherapy side-effects patients with recurrent medulloblasA new gene-therapy technique to combat adverse effects of high-dose toma is very low. In the 23 patients chemotherapy has been found to be safe in a phase I clinical trial. The treated with the new regimen, the technique involves harvesting haemopoietic stem cells and treating one-third of investigators report a 35–45% eventthose cells with a retrovirus that contains the DNA for the multiple-drugfree and overall survival at 36 months resistance gene (MDR). The cells are then re-infused into the patient, as part of post-treatment. These results are an autologous stem-cell transplant. The presence of MDR makes the stem cells encouraging for future treatment resistant to the chemotherapeutic agents used to combat the cancer. The trial and long-term survival for patients findings show that the technique is safe. But, only two of the five patients with recurrent medulloblastoma, treated showed evidence of the exogenous MDR gene in their bone marrow up say the authors.
ew regimens of intensive chemotherapy and bonemarrow rescue may be beneficial for certain malignant brain tumours, according to two studies reported in the Journal of Clinical Oncology (1998; 16: 210–21; 222–28). The first regimen, aimed at newly diagnosed brain malignancies in young children, lasts only 6 months, compared with the usual treatment time of 1–2 years. This “head-start protocol” seems to increase overall survival and event-free survival rates, compared with known rates for standard protocols. An added benefit is that the new regimen does not include radiation to the brain. A team led by Jonathan Finlay (New York University Medical Center, NY, USA) treated 62 children, all under the age of 6, with malignant brain tumours. Every 3
SPL
N
to 10 weeks after transplantation. Larger efficacy trials are needed. Hannah Wunsch
Dilated cardiomyopathy carries risk for relatives
R
elatives of people with dilated cardiomyopathy are themselves highly likely to develop heart failure, according to a new study. Investigators in London, UK, studied 408 symptom-free relatives of 110 patients with dilated cardiomyopathy. 29% of relatives had an abnormal echocardiogram, with left-ventricular enlargement (LVE) being the most common abnormality. During more than 3 years of follow up, 27% of relatives with LVE developed dilated cardiomyopathy. These results suggest that the degree to which dilated cardiomyopathy is a familial disease has been seriously underestimated (J Am Coll Cardiol 1998; 31: 195–201). “In the past, we’ve only been able to identify people with dilated cardiomyopathy when they turn up with the signs of heart failure, such as breathlessness, palpitations, or fainting episodes”, said Kamran Baig (St George’s Hospital Medical
116
School, London, UK). “Although we’ve thought for some time that dilated cardiomyopathy runs in families, it’s been difficult to assimilate this knowledge into clinical practice.” It remains unclear, however, exactly how clinical practice should change. “What we don’t know just yet is whether or not any early intervention will be beneficial”, said Baig. “Our present policy after we identify people with LVE is to follow them on a yearly basis with non-invasive tests, looking for any indication of a change for the worse in their hearts. When we spot someone who is deteriorating, we start them on what we think is appropriate therapy, most often ACE [angiotensin-convertingenzyme] inhibitors, which have been shown to be effective in the early stages of heart failure.”
News in brief T-cell key in type 1 diabetes Patients with type 1 diabetes (IDDM) have T cells predisposed to attack their own pancreatic cells. But, progression to diabetes also involves a specific T-cell subset— the loss of these cells’ ability to secrete interleukin 4 correlates with IDDM (Nature 1998; 391: 177–81). Neurodegeneration unravels The abnormal protein deposits seen in non-familial Alzheimer’s disease and Down’s syndrome contain aberrant forms of ubiquitin- and amyloid precursor protein. But the abnormal proteins are likely to result not from mutations in the encoding DNA but from “frameshift” mutations in the RNA transcripts (Science 1998; 279: 242–47). The authors suggest that transcriptional mutation “may underlie a number of neurodegenerative pathologies”.
Larry Husten
THE LANCET • Vol 351 • January 10, 1998