Use of belatacept as alternative graft vs host disease prophylaxis in pediatric allogeneic hematopoietic stem cell transplantation

Abstract

Background Immunosuppressive prophylaxis is usually given to decrease the development of acute graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Belatacept is a Cytotoxic T‐lymphocyte‐associated protein 4, blocking agent, an immunosuppressive agent used for organ rejection prevention in adult renal transplant recipients. Methods We describe two children in whom belatacept was successfully used for GvHD prophylaxis. Case 1 was noncompliant with prior immunosuppressive therapy for aplastic anemia, and Case 2 developed severe thrombotic microangiopathy (TMA) precluding the use of calcineurin inhibitors (CNI) or mTOR inhibitors. Results and Conclusion Belatacept was found to be a safe alternative in preventing GvHD in 2 patients in whom traditional prophylactic therapies were not possible to use.

A Difficult Case of Calcineurin Inhibitor Neurotoxicity Post-Haploidentical HCT With a Successful Novel Solution: Cytotoxic T-Lymphocyte-Associated Protein 4-Immunoglobulin Blockade for GVHD Prophylaxis

“…CTLA4-Ig blocking agents include abatacept and belatacept. These are modified antibodies that block activation of cytotoxic T-cells by binding to CD80 and CD86, preventing interaction with CTLA-4/CD28, leading ultimately to costimulation blockade ( Figure 3 ) 16 – 18 . The two-signal model of T-cell activation dictates that, for T-cell activation to proceed, two signals are required: one through the antigen-specific T-cell receptor (TCR) and the second though the non-antigen-specific engagement of a costimulatory molecule by its counterpart on an antigen presenting cell.…”

“…Although not currently approved for use in HCT, belatacept is a second-generation form of abatacept with two different amino acid substitutions that allow for high binding affinity to CD80 and CD86 18 . Belatacept is approved for immunosuppression in adult kidney transplant and is an effective option for patients unable to tolerate CNIs, despite a slightly higher risk of acute organ rejection 26 .…”

“…Belatacept is approved for immunosuppression in adult kidney transplant and is an effective option for patients unable to tolerate CNIs, despite a slightly higher risk of acute organ rejection 26 . To date, there has been one publication of two pediatric patients who successfully underwent HCT with belatacept as GVHD prophylaxis 18 . One patient was a teenager with severe aplastic anemia who was noncompliant with immunosuppression pre-transplant and then underwent matched-related donor (MRD) HCT; thus, parental belatacept was given after a short course of tacrolimus and MTX to minimize complications related to medication nonadherence to GVHD prophylaxis.…”

Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

“…Another co-stimulation blocker, belatacept, has also been used clinically for GVHD prophylaxis in patients with TA-TMAs and inpatients after solid organ transplant who did not tolerate CNIs. 68 8.2 | Going "back to the basics"…”

“…Abatacept could therefore be considered in TA‐TMA patients who are required to stop CNIs and are at high risk for acute GVHD. Another co‐stimulation blocker, belatacept, has also been used clinically for GVHD prophylaxis in patients with TA‐TMAs and inpatients after solid organ transplant who did not tolerate CNIs 68 …”