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.