Minimal residual disease in peripheral blood compared to bone marrow in patients treated for acute myeloid leukemia

Patients with acute myeloid leukemia (AML) undergo multiple bone marrow (BM)
aspirations. The first collection is needed to make the diagnosis and with
subsequent punctures therapeutic outcome is assessed and any residual leukemic
cells are measured ("Measurable Residual Disease" (MRD)) to establish Complete
Remission (CR) and guide consolidation treatment. A positive MRD result in BM
is strongly associated with the development of relapse and poorer survival for
the patient. The level of MRD is lower in peripheral blood (PB) compared to BM,
but previous research has shown that MRD can nevertheless also be measured with
a high specificity in PB. But the prognostic value of MRD in PB has never been
examined. Because MRD may also be used for early prediction of relapse during
and after therapy, it has to be measured more frequently at multiple time
points. BM aspiration is a painful and expensive procedure, therefore it would
be of great benefit to the patient if the BM sample could be replaced by a PB
sample. Especially during therapy, almost all patients have a central venous
catheter, which makes blood collection less invasive.

Our research aims to determine and compare MRD in BM and PB with our current
qualified MRD test. The study takes place in at the Amsterdam UMC location
VUmc. We take two extra tubes (14 ml total) of heparin blood at the same day as
the planned BM sampling in AML patients. The most important outcome is to
compare the standard BM-MRD value with PB-MRD for each collection point during
and after treatment. We will probably find a lower sensitivity, which may be
counterbalanced by an increase in specificity in PB, making it still relevant
for prediction of relapse. In addition, we will measure and compare leukemic
stem cells (LSC) in both materials, since the LSC frequency is currently
prospectively being evaluated as prognostic factor for relapse and survival as
well. If a good concordance between the two materials is demonstrated, this may
lead to replacement of the BM aspiration with PB during and after therapy.

This is an observational study in which the MRD levels in PB will be compared
with those in BM. Patients will be approached for participation by their
treating physician, researcher or nurse.
We expect a maximum of 50 patients to be eligible for inclusion per year at
location VUmc and 15 per year at location AMC. Therefore, we hope to reach the
desired amount of inclusions within 3 years after the start of the study. After
last inclusion, patients will be followed for an additional year.

After enrolment, we will ask for two extra tubes of PB on the day the patient
undergoes a BM aspiration. The number of blood samples per patient will differ,
but on average we expect to collect three separate PB samples per patient. Most
patients will already have an central venous catheter as part of the standard
treatment. In which case, the blood will be drawn from this catheter.