Table 1.
Literature Review of Haploidentical Hematopoietic Cell Transplant (HCT) Utilizing Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4-Ig) Blockade for Graft-Versus-Host-Disease (GVHD) Prophylaxis.
| First author, Year | Type of study (N) | Indication for transplant (malignant/nonmalignant) | GVHD prophylaxis | Acute GVHD | Chronic GVHD | Relapse rate | Outcomes |
|---|---|---|---|---|---|---|---|
| Jaiswal et al, 2016 30 | RCT, pediatric haploidentical HCT (N = 20) | Nonmalignant (SAA) | PTCy, siroliums ± abatacept | 10.5% in intervention group vs 50% | NA | NA | GVHD-free and disease-free survival at 1 year was 80% in pts treated with abatacept vs 30%. |
| Jaiswal et al, 2020 31 | Observational, pediatric haploidentical HCT (N = 10) | Nonmalignant (hemoglobinopathies) | Short course low dose dexamethasone, abatacept, siroliums for 6 months. | None | None | NA | No pts developed GVHD at time of median follow-up, 28 months. |
| Raffa et al, 2021 32 | Observational, pediatric haploidentical HCT (N = 4) | Malignant and nonmalignant (erthropoietic porphyria, primary immunodeficiency; second HCT for CML and AML) | Abatacept + MTX, MMF, and CNI (none received PTCy) | 2 cases, grade 2, steroid-responsive (skin, skin and gastrointestinal) | 2 cases, mild limited to skin | None | At 1.1 year, all four pts were alive with full chimerism. three were off immunosuppression. |
| Kharya et al, 2023 33 | RCT, pediatric haploidentical HCT (N = 79) | Nonmalignant (SAA) | PTCy, CNIs/siroliums ± abatacept | 26.4% | 18.9% | NA | OS and EFS were better and MVA found less GVHD in the pts treated with abatacept. |
| Al-Homsi et al, 2023 25 | Phase1b-2 clinical trial, haploidentical HCT (N = 46) | Malignant | PTCy, abatacept (days +5, +14, +28, and +56) and tacrolimus days +5 to +90 | Grades 2 to 4: 17.4%, grades 3 to 4: 4.4% | Moderate-severe 15.9% | 11.7% | Acute GVHD after haploidentical HCT was safe and effectively reduced. |
The literature search was conducted from 2013 (year of first in human CTLA4-Ig blockade in human HCT) to April 2024. PubMed and Google Scholar databases were searched. Search terms included “CTLA4-Ig haploidentical HCT,” “abatacept haploidentical HCT,” and “belatacept haploidentical HCT.” RCT: randomized control trial; MVA: multivariate analysis; SAA: severe aplastic anemia; SCD: sickle cell disease; Flu: fludarabine; Cy: cyclophosphamide; ATG: antithymocyte globulin; TBI: total body irradiation; TT: thiotepa; Mel: melphalan; PTCy: post-transplant cyclophosphamide; CNI: calcineurin inhibitor; MTX: methotrexate; MMF: mycophenolate mofetil; OS: overall survival: AML: acute myeloid leukemia; CML: chronic myeloid leukemia; EFS: event-free survival; pts: patients.