Research

I promised to discuss the new research project for which Nanda had to sign a consent form and hand in yesterday.

First of all, it does not involve new or extra bone marrow or blood samples. It just involves existing bone marrow samples taken during her first four weeks of treatment.

I haven´t seen the whole consent letter but my brother summarised for me “the scientific part”. To quote:

“The aim of the study is to measure the levels of angiogenesis, MDR-1, MRP and indicators of hypoxia in the bone marrow samples taken routinely at diagnosis. These measures would then be related to the speed and extent (the level if any of minimal residual disease) of your child's response to the first four weeks of treatment. This is to help further understanding of the variations in the speed and extent to which the leukemia cells disappear from the bone marrow during the first four weeks of treatment. In many adult cancers the numbers of new blood cells (angiogenesis) and a low level of oxygen within the cancer (hypoxia) are recognised as making the tumours less responsive to treatment. It is not yet known whether the numbers of new blood vessels or low oxygen levels are important for making the treatment of childhood ALL more difficult. Also some cancers contain resistance proteins (MDR-1 and MRP) that may reduce the effectiveness of drugs such as vincristine.”

As I haven´t seen the whole consent document, I am not sure of the rest of its contents.

I am sure this consent letter has not been translated into the principal minority languages of England – Urdu, Punjabi etc – the principle ethnic minority languages of he hospital´s catchment area - let alone Nanda´s native language, an official language of the European Union. I am afraid that ethnic minorities, or many others with little literacy (whether UK or non-UK readers, writers, listeners or speakers of English) and those who don´t have a first idea about the science, are left in the dark.

UKALL 2003 - Vincristine

Another drug derived from a natural source – the Madagascan Periwinkle Caranthus roseus. The plant has been in use in traditional medicine for centuries treating anything from diabetes to wasp stings to eye infections. When scientists began looking at it in the 1950s, they discovered over 70 alkaloids among which was vincristine.

Microtubules form part of the structural network, or cytoskeleton, of a cell's cytoplasm. They are made of a protein called tubulin. They form various structures and have various functions. One of these is the formation of a structure called a mitotic spindle (mitosis = cell division). This segregates chromosomes correctly during cell division so that each daughter cell receives the correct number of chromosomes. In the picture below the mitotic spindle is green and the chromosomes are blue.

Vincristine binds to tubulin and prevents the formation of microtubules and, in particular, the mitotic spindle. Thus the cell dies without being able to divide.

Unlike our other chemotherapy agents so far, this is not working directly on the cell nucleus and DNA but within the cell's cytoplasm surrounding the nucleus.

It has, like all our drugs, many side-effects. Particularly, noticeable are neurological effects – Kezia developed tingling feet making her unwilling to walk. Others report similar effects.

If given intrathecally (in the spine), it is fatal. For this reason the UKALL 2003 protocol gives the following warning:

“All medical staff involved in the care of patients with leukaemia MUST be aware that the inadvertent administration of vincristine by the intrathecal route is invariably FATAL. Vincristine should NOT BE AVAILABLE when an intrathecal needle is in situ. This protocol has been written to provide separation of intrathecal methotrexate administration from intravenous vincristine administration in time. An additional precaution is that the two drugs should not be administered in the same place.”