I spoke about minimal residual disease in adult acute lymphoblastic leukaemia. Essentially minimal
residual disease, MRD, is what remains of the disease after the patient has been brought into
complete hematologic remission, which is the essential condition to be cured – we try to cure these
patients. So minimal residual disease that can be assessed by means of flow cytometric methods or,
more typically, by molecular biology, PCR reaction, is the remnants of the original leukemic burden.
With current methodology we can detect one leukemic cell in individual patients out of 10,000,
100,000 normal marrow cells. The disease can be followed after repetitive chemotherapy courses in
remission patients and the information that we gather by looking for and finding MRD is that some
patients harbour MRD in their remission marrows whereas other patients do not. It makes a big
difference because if we can’t find MRD it means that the patients respond well to the chemotherapy
programme being administered and this prognosis is much better than patients in whom we can
detect, we can trace, MRD. It’s kind of a chemosensitivity test in other words.

So we can reclassify the patients, once in remission, according to the MRD results regardless of the
initial risk category which is defined by clinical criteria, say the genetics of the disease, the white cell
counts, the phenotype and so on; we can use different combinations. But, nevertheless, once we
detect minimal residual disease after a consistent amount of consolidation chemotherapy, that patient
is always a high risk patient so we can reclassify the patients, both the standard risk or the high risk,
into MRD positive or MRD negative. It makes a lot of difference.

From the information, from the historical information, we know that the MRD positive patients have a
long-term survival probability of about 25% only, say adult ALL Philadelphia negative, whereas for the
MRD negative, regardless of treatment we can skip safely to transplantation, the probability of survival
is in the rage of 70-80%. So it helps deciding the final treatment. We go to that. The MRD positive is
always selected for transplantation from sibling donors or family unrelated donors because it’s well-
known that performing a transplant in this category of patients improves outcome compared to normal
transplant from 20%, 10%, to an average of 50%. It’s still problematic because the MRD positive
patients are difficult to transplant. Many relapse due to MRD positivity before transplant and some
relapse after transplant. So the new concept is that we have to introduce, we have to look for novel
treatments, novel strategies, to improve the MRD status, to prolong the disease free interval in order
to be able to achieve the transplant procedure and to improve the post-transplantation outcome. This
is the field of the novel immunotherapies – CAR T-cells, the monoclonal antibodies, we can use other
targeting agents. It’s a new world of treatments under construction.