By Dr. Mikael Rørth, M.D. and Professor at Rigshospitalet in Copenhagen

Leukaemia is the most frequent malignant disease among children. In Denmark, there are around 100 new cases every year. Until the middle of the last century, it was always a quick fatal disease: Half of the leukaemia children were dead within three months after having been diagnosed, and they had all died within nine months.

The medical treatment with cytotoxic drugs ("chemotherapy") was introduced in the 1950’s and has undergone a rapid development since then. In the following decades, the treatment was perfected to such a degree that up to 70% of all children with leukaemia can now be cured using chemotherapy. The treatment consists of the induction treatment, followed by the consolidation and the maintenance treatment. Furthermore, radiation treatment is used against the central nervous system. Through clinical studies it has been possible to identify factors, which characterise those patients with the smallest chance of responding to the "standard treatment" (prognostic factors) – thereby identifying the patients, who should be treated more intensively.

With these patients and with patients who relapse, transplants with stem cells from healthy individuals (bone marrow transplant) offer new possibilities for a cure.

Sources for stem cells
Stem cells for treatment can be found in three places with the donor: 1. Bone marrow, 2. Peripheral blood and 3. Umbilical cord blood. Most transplants are done with bone marrow cells, but in recent years, for children, both peripheral stem cells from blood (>20%) and stem cells from umbilical cord blood (>10%) have been used. Bone marrow cells can be "harvested" in one swoop without pre-treatment and it less often causes "graft versus host disease" (GvHD)" than peripheral stem cells. The drawback is that it requires total anaesthetisation of the donor.

It is the so-called HLA-tissue types, which determine the compatibility, i.e. how well the patient=recipient receives the stem cells from the donor. In this connection we talk about four different types of donors: 1. Identical twins, where the HLA-types are identical. 2. HLA-identical siblings, where the differences are negligible. 3. Other family donors, for example a parent and 4. Non-related donors. The greater incompatibility, the greater the risk for GvHD. Within the last five to ten years donor files have been established in Europe and the US with six million potential donors, which have all been registered according to tissue type. This means that in 80-90% of all cases it is possible to find a donor.

Pre-treatment
Prior to a transplant, the recipient=patient must be pre-treated, i.e. conditioned. The purpose of the conditioning is 1. to make room for the stem cells in the bone marrow of the patient, 2. suppress the immune system to avoid rejection and 3. exterminate leukaemia cells.

Normally the conditioning consists of radiating the entire patient, and giving chemotherapy in the shape of large doses of cyclophosphamide (up to 200 mg per kilo body weight). If possible, radiation of small children (< 4 years) is avoided to prevent brain damage.

The conditioning has the effect that the patient does not produce any blood cells. After the conditioning, the stem cells (the transplant) are injected into the blood stream just like a transfusion. The stem cells settle in the bone marrow and in the course of a couple of weeks blood samples can determine that white and red blood cells and blood platelets are being produced by the new stem cells. This means that the critical period is the first few weeks after the conditioning, when the patient is totally without immune defence and furthermore lacks blood platelets which creates the risk of haemorrhage. Therefore the patient is admitted to a special ward and isolated to minimise the risk of infection.

Complications
The obvious, life threatening complications to this treatment, apart from infections and haemorrhages, are recurrence of the leukaemia, GvHD disease, the so-called interstitial pneumonia, and other forms of organ failure. Complications later on, are for instance other malignant diseases, which especially occur with those patients, who have received radiation treatment. Furthermore hormonal disturbances, especially growth inhibition, delayed puberty etc. With this intensive treatment, you can cure more than 50% of those patients, who would otherwise die from their disease.

Nowadays, most survivors become almost completely asymptomatic after a period of four to twelve months. Patients with chronic GvHD disease require frequent treatment (with cyclosporin and/or glucocorticoid) for one to three years. Progress can be expected both within the treatment itself, i.e. the handling of the side effects and with the identification of the best donor for the individual patient. Finally, work is being done with new forms of transplantation, where the immune system of the patient is only partially inhibited during the process ("mini-transplantation"), which make life threatening situations less likely.