Stem cells jab 'helps brain cancer patients tolerate chemotherapy'

Daily Mail Reporter


21:01 GMT, 9 May 2012



06:37 GMT, 10 May 2012

Stem cells have been transplanted into brain cancer patients for the first time in a bid to protect them against the toxic side effects of chemotherapy.

In a study involving three patients, scientists found that two of them survived longer than predicted following the surgery while the other has seen no disease progression after three years of treatment.

The study was carried out by the Fred Hutchinson Cancer Research Centre in the United States.

Breakthrough: Scientists have transferred stem cells into brain cancer sufferers in a bid to protect them against the harmful effects of chemotherapy

Breakthrough: Scientists have transferred stem cells into brain cancer sufferers in a bid to protect them against the harmful effects of chemotherapy

The centre's Dr Hans-Peter Kiem said: 'We found that patients were able to
tolerate the chemotherapy better and without negative side effects after
transplantation of the gene-modified stem cells.

'This compares with patients in
previous studies who received the same type of chemotherapy without a
transplant of gene-modified stem cells.'

Dr Kiem added that a major barrier to
effective use of chemotherapy to treat cancers such as glioblastoma, which all three patients had, has
been the toxicity of chemotherapy drugs to other organs, primarily bone

This results in decreased blood cell counts, increased susceptibility to infections and other side effects.

Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, published in the journal Science Translational Medicine, Dr Kiem and his colleagues focused on patients with glioblastoma, an invariably fatal cancer.

Many of these patients have a gene called MGMT – O6-methylguanine-DNA-methyltransferase – that is turned on.

MGMT is a DNA repair enzyme that counteracts the cancer-killing effect of some chemotherapy agents such as temozolomide, so such patients have a particularly poor prognosis.

Study: Dr Hans-Peter Kiem undertook the research

Study: Dr Hans-Peter Kiem undertook the research

A drug called benzylguanine can block the MGMT gene and make tumour cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumour cells are still sensitive to chemotherapy.

Dr Kiem said: 'P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine.'

The three patients in the study survived an average of 22 months after receiving transplants of their own circulating blood stem cells.

One, a man from Alaska, remains alive 34 months after treatment.

Average survival for patients with this type of high-risk glioblastoma without a transplant is only just over a year.

Dr Adair added: 'Glioblastoma remains one of the most devastating cancers with a median survival of only 12 to 15 months for patients.'

As many as 50 per cent to 60 per cent of glioblastoma patients harbour such chemotherapy-resistant tumours, which makes gene-modified stem cell transplant therapy applicable to a large number of them.

And there are also other brain tumours, such as neuroblastoma or other solid tumors with MGMT-mediated chemo resistance, that might benefit from the same approach.

The researchers also found that chemotherapy increased the number of gene-modified blood and bone marrow cells in these patients.

Dr Kiem said this finding will have implications for other stem cell gene therapy applications where defective bone marrow stem cells can be corrected by gene therapy but their numbers need to be increased to produce a therapeutic benefit, or for patients with HIV/AIDS to increase the number of HIV-resistant stem and T cells.