Relapse occurs when:
- There are more than 50% lymphoblasts in a single bone marrow aspirate.
- Progressive repopulation of lymphoblasts in marrow by >5% leading to more than 25% lymphoblasts in samples separated by at least a week.
- More than 25% lymphoblasts in the bone marrow and 2% or more circulating lymphoblasts in the bone marrow.
- Extramedullary leukemic cell infiltration of organs such as CNS and testes. In an isolated extramedullary relapse the marrow should have less than 5% blasts.
- CSF lymphoblast count greater than 5 WBC/mm3
Bone Marrow Relapse
This is the commonest site of relapse and occurs in up to 25% of children with ALL.
Relapse may be isolated in the bone marrow or associated with other sites - generally CNS and or testicular relapse.
If BM relapse occurs before completing therapy or within 6 months of therapy completion, their prognosis is very poor.
If BM relapse is more than 6 months from therapy completion, then the prognosis is much better.
CNS prophylaxis has significantly reduced the risk of CNS relapse
In the late 1980s and early 1990s the risk of CNS relapse was about 50 - 60%.
The risk of relapse is now much lower.
Recent chemotherapy regimens use intensive chemotherapy with drugs that have good CNS penetration and delayed radiation therapy (RT) to treat isolated CNS relapse.
Duration of initial remission is the most important prognostic factor. The 4 year EFS is much better if the initial remission was longer than 18 months.
Intrathecal chemotherapy alone fails to cure CNS relapse. There is evidence that 18 Gy whole brain RT is sufficient therapy (see guidelines in CNS Disease).
This has become very uncommon and the overall risk of testicular relapse in boys with ALL is about 2%.
There is a barrier preventing drug entry into the seminiferous tubules.
Again the most important prognostic factor is the length of initial remission.
Principles of therapy involve re-induction, ongoing chemotherapy, CNS prophylaxis and bilateral testicular RT (see guidelines in Testicular Disease).