INTRODUCTION
The platform of haplo-HCT has changed dramatically in recent decades,
specifically with the introduction of post-transplant cyclophosphamide
(PTCy) (1, 2). Several groups have since combined the use of PTCy and
anti-thymocyte globulin (ATG), with varying doses, in an effort to
further reduce GVHD with haplo-HCT when a PBSC graft is used (3-6). This
regimen was shown to reduce the incidence of both acute and chronic
GVHD, had lower NRM, with similar long term transplant outcomes. This
highlights the possibility of preserving a good outcome post haplo-HCT
with a variation in the standard use of PTCy alone.
Haplo-HCT with PTCy has been successfully used as salvage therapy in
situations where the initial non-haplo HCT has failed. However, with the
increasing popularity and success of haplo-HCT, we find ourselves facing
unique challenges (7, 8). Although there are reports of a small number
of adult patients in the literature who experienced graft failure or
loss who were re-transplanted with a haploidentical donor with PTCy
prophylaxis as well, there is still insufficient guidance for patients
with specific contraindications/complications to cyclophosphamide and
virtually no data in the pediatric setting (9-13). The concern regarding
further use of cyclophosphamide may include, but is not limited to,
recent exposure and significant cumulative dose of cyclophosphamide and
presence of secondary organ toxicity such as cardiac dysfunction or
urinary tract toxicity. Abatacept, a soluble fusion protein composed of
the extracellular domain of human cytotoxic T-lymphocyte -associated
antigen 4 (CTLA-4) linked to the modified Fc portion of human
immunoglobulin G1, selectively inhibits T cell co-stimulation by
blocking CD28 mediated signaling (14). It therefore can attenuate T cell
activation giving it the potential to mitigate GVHD (15). Abatacept
earned the breakthrough designation from the US Food and Drug
Administration for protection against acute GVHD in 2019 (16, 17).
In this single center retrospective study, we describe the use of
abatacept for GVHD prophylaxis in four patients. This is the first
report to describe the use of abatacept as an alternative to the PTCy
approach in haplo-HCT in the malignant setting. The standard PTCy
regimen had been avoided in these patients either due to previous
exposure to PTCy or when administration of PTCy would not be appropriate
due to their underlying disease or organ dysfunction.