Leukaemia in twin children
Leukaemia in one or both children who are identical twins has the same clinical and biological features as children who are not twinned. Cure rates for the most common form of leukaemia in childhood - acute lymphoblastic leukaemia (ALL) are now around 90%, and this applies whether or not a child has an identical twin.
What often concerns parents when leukaemia is diagnosed in twins is whether it has been inherited. And when only one twin in an identical pair is diagnosed, questions may relate to the second twin’s risk of developing leukaemia.
Here is a summary of what we currently understand about ALL in identical twin children.
What causes ALL?
Inherited susceptibility plays a role in risk of childhood ALL, as in most if not all cancers of children and adults, but it is not the primary cause of ALL in a pair of twins.
We suspect the most likely cause of ALL in twins, as in non-twinned patients, is an abnormal immune response to common infections, and that this abnormal response probably occurs because of deficiencies in the infant’s gut microbiome. Beneficial bacteria in the gut train the developing immune system but sometimes, through no fault of the parents, this process doesn’t work as well as it should.
When does ALL start to develop in children?
We know from several lines of evidence that childhood ALL usually starts in the womb before birth when one immature blood cell in the developing baby acquires a DNA coding error or mutation.
Why are identical twins sometimes both diagnosed with leukaemia?
Identical twins can sometimes both go on to develop ALL. This almost always happens when identical twins have shared a single placenta in the womb. It’s estimated that 60% of identical twins share one placenta. Non identical twins never share a single placenta.
In single placentas the blood vessels make connections that allow passage of fluid and cells between the blood systems of the paired babies. This means the twins literally share each other’s blood. If one twin in a shared placenta develops blood cells with a leukaemia mutation then those cells will inevitably be shared with his/her co-twin. As a consequence both twins may later develop leukaemia.
Do identical twins always both get ALL?
If one twin in an identical pair who shared a single placenta is diagnosed with ALL, it is not inevitable that the second twin will also be diagnosed. The most common variant of ALL - B cell precursor - is mostly diagnosed between the ages of two and six, and the risk of the same diagnosis for the second twin is relatively high at around 15 to 25%. The risk is highest during the year after the first twin is diagnosed and falls off sharply after that.
An identical twin who remains ALL free despite a diagnosis in her/his twin sibling still has the shared mutated blood cells acquired before birth. The reason this does not inevitably result in a diagnosis of ALL is that this cancer requires not one but two mutational hits. The second hit occurs (possibly because of infection) during childhood and may not happen. We know that non-twinned babies can acquire the first mutation in the womb but, similarly, most do not develop ALL. We say that that first mutation is necessary but not sufficient for ALL.
ALL in infants
A rare and clinically aggressive form of leukaemia can occur in infants (less than 18 months). These ALL have a unique mutation that also occurs in the womb but appears to be sufficient by itself for leukaemia to develop. For that reason, if an infant identical twin is diagnosed with this variant of ALL his/her co twin has a high risk of the same ALL, close to 100%. But again, only if there was a single placenta.
If one twin is diagnosed with ALL, should the other twin’s blood be screened?
Where one twin in a pair has a diagnosis of ALL and the twins were identical and shared a single placenta it may be prudent to screen the blood of the healthy co -twin for the presence of cells having the same mutation.
These cells are expected to be there but at very low levels. If those cells increase in number then this may signal development of ALL and prompt consideration of a bone marrow biopsy and possible early instigation of treatment.
If the healthy co twin has persistent very low levels or negligible numbers of cells carrying the first mutational hit present in the sibling with ALL this provides reassuring evidence that clinical ALL is not developing.
Who can carry out mutational screening?
Mutational screening does require specialised knowledge and technical skills and is best carried out by centres or teams with expertise in leukaemia molecular genetic diagnoses.
Written by Professor Mel Greaves and Dr Anthony M. Ford,
Institute of Cancer Research, London, September 2022
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