Do Serum Alemtuzumab Concentrations Predict Donor T Cell Chimerism after Non-Myeloablative Matched Sibling Donor Stem Cell Transplantation in Sickle Cell Disease Patients? (PREDICT study)

Non-myeloablative allogeneic stem cell transplantation (SCT) has become a
feasible curative treatment option for sickle cell disease (SCD) patients with
an available matched sibling donor. Chemotherapy free conditioning with
alemtuzumab and 3 Gy total body irradiation (TBI) is increasingly being used as
preferred conditioning scheme for these patients. This regimen typically
results in mixed donor chimerism and has only few toxic effects. However, the
risk of graft failure (rejection) is still significant, with an occurrence of
13% in the latest series. Levels of T cell chimerism are crucial for the
success of this kind of transplantation. A donor T cell level of at least 50%
at 1-year post-transplantation seems to be sufficient to allow the
discontinuation of immunosuppressive medication without risk of graft
rejection. Low levels of alemtuzumab prior to or shortly after SCT are thought
to facilitate rejection of the donor graft. Recently, a positive correlation
between alemtuzumab levels on day+14 was found with levels of T cell chimerism
+2 and +4 months post-transplantation in adult SCD patients receiving matched
sibling donor SCT. However, in this study alemtuzumab levels prior to the
infusion of hematopoietic stem cells and beyond day +28 post-transplantation
were not measured. Furthermore, the alemtuzumab levels were measured in 2
patient groups undergoing two different conditioning regimens.
Here, we aim to thoroughly investigate the correlation of alemtuzumab levels
and T cell chimerism. To our knowledge, this will be the first study involving
SCD patients receiving matched sibling donor SCT with alemtuzumab/TBI
conditioning that includes alemtuzumab level measurements before the infusion
of hematopoietic stem cells and beyond 1-month post-transplantation. Findings
from this study will improve the insights into the etiology of graft failure in
these patients and might ultimately lead to a more personalized approach in
dosing alemtuzumab in order to achieve a more robust and stable engraftment of
donor hematopoietic stem cells.

To investigate whether serum alemtuzumab concentrations are predictive of the
robustness of engraftment in SCD patients undergoing a matched sibling donor
transplantation with alemtuzumab/TBI conditioning resulting in mixed chimerism.

Prospective observational laboratory study. Serum alemtuzumab concentration
will be measured at various time points before and after stem cell infusion
(days -3, 0, +7, +14, +28, +60).

For subjects included in this study no direct positive effect can be expected.
The burden for participants will be limited to 4 ml extra blood being drawn
when routine blood tests are planned. Time points T0 and T3 might not coincide
with routine blood examinations. However, these samples will be drawn via a
central venous catheter, leading to minimal burden and no risk to the patients.
Findings from this study could lead to a more personalized approach in future
patients in whom alemtuzumab doses could be adjusted to further reduce the risk
of graft rejection.