A trial looking at treatment for haemophagocytic lymphohistiocytosis (HLH) in children and young people (HLH 2004)

Cancer type:

Children's cancers

Status:

Results

Phase:

Phase 3

This trial looked at initial treatment for children and young people with haemophagocytic lymphohistiocytosis (HLH).

More about this trial

HLH is a rare condition where the body produces too many white blood cells called lymphocytes and histiocytes. If it is not treated, these extra cells collect in organs in the body and damage them. HLH is not cancer, but it is similar to cancer and usually treated by cancer specialists.

There are two different forms of HLH:

primary HLH develops because of an inherited genetic change (mutation)
secondary HLH develops because of a problem with the immune system such as an infection

A trial called HLH 94 looked at treatment with etoposide chemotherapy and the steroid dexamethasone to begin with (initial therapy). And then etoposide, dexamethasone and cyclosporin after that (continuation therapy). Cyclosporin is a drug that dampens down the immune system.

This treatment works quite well, but doctors hoped that having etoposide, dexamethasone and cyclosporin together from the beginning may be better.

The aim of the HLH 2004 trial was to find out how well etoposide, dexamethasone and cyclosporin work as initial treatment for primary and secondary HLH.

Summary of results

This trial showed that having etoposide, dexamethasone and cyclosporin as initial treatment was not better for people with haemophagocytic lymphohistiocytosis (HLH).

This trial recruited patients between 2004 and 2011, and the results were reported in 2017.

Results

The trial recruited 369 children and young people from 27 different countries. Of those taking part:

168 had primary HLH
201 had secondary HLH

Everyone taking part had etoposide, dexamethasone and cyclosporin as initial treatment. Some people went on to have a stem cell transplant.

The research team looked at how many people were living 5 years after joining the trial. They found it was just over 6 out of 10 people (61%). When they looked at the different types of HLH they found it was:

just under 6 out of 10 people (59%) who had primary HLH
more than 6 out of 10 people (64%) who had secondary HLH

The number of people living at 5 years in the HLH 94 trial was more than 5 out of 10 (54%). So there was not much difference between the two.

Of the 188 people who went on to have a stem cell transplant, 121 (66%) lived for at least 5 years. This is the same percentage as the HLH 94 trial.

Side effects

The treatments used in this trial have all been used to treat cancer, and other conditions, for a number of years. The people taking part in this trial didn’t have any unexpected side effects.

A few people had serious side effects such as:

problems with the brain which may cause fits or learning difficulties
problems caused by high blood pressure
liver problems
infections

One person went on to develop acute myeloid leukaemia (AML).

Conclusion

The trial team concluded that it was not better to include cyclosporin in initial treatment for HLH. They recommend that children and young adults with HLH continue to have etoposide and dexamethasone at the start of treatment.

They suggest that it might be useful to look at other treatments alongside standard treatment. This could include monoclonal antibodies or other targeted drugs.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item

) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.