Timing of alemtuzumab with respect to day of bone marrow infusion and
its effects upon engraftment and graft-versus-host disease in patients
with hemoglobinopathy: A single institutional study.
Abstract
Background: Reduced intensity conditioning followed by allogeneic
hematopoietic stem cell transplantation can often be curative for the
treatment of hemoglobinopathies. Procedure: This is a prospective
IRB-approved (NCT02435901) clinical trial, reporting the possible impact
of “late” alemtuzumab (administered on days -10 to-8) versus “early”
alemtuzumab (-19 to -17) with respect to engraftment and acute/chronic
graft-vs-host disease (GvHD) in a group of 35 pediatric patients with
sickle cell disease (SCD) or thalassemia undergoing bone marrow
transplantation (BMT) following conditioning with alemtuzumab,
fludarabine and melphalan. The first 9 patients with SCD received
“late” alemtuzumab followed by BMT from HLA matched siblings (MSD).
The next 26 patients (21 with SCD and five thalassemia major) received
“early” alemtuzumab. Of the 26 patients, 17 received transplant from
MSD and nine from matched unrelated donors (MUD). Results: In the
“late” group, one patient (11%) developed acute GvHD, six (67%)
achieved sustained engraftment. Three patients (33%) ultimately
experienced graft rejection, leading to early termination of enrollment
of patients on this regimen. In the “early” alemtuzumab group, acute
and chronic GvHD developed in 50% and 34% patients, respectively none
of the patients experienced graft rejection. Three patients died, 2 due
to GvHD-related complications and 1 from sepsis. Five patients developed
stable mixed chimerism while 14 demonstrated 100% donor chimerism at
one year post-transplant and beyond. Conclusions: These results suggest
a benefit with respect to engraftment of administering “early” vs
“late” alemtuzumab in this RIC regimen but with the possible cost of
an increase in acute, and possibly chronic GvHD.