Bone Marrow Transplantation from Alternative Donors in Children Receiving Rabbit ATG for Prophylaxis of Graft-Versus-Host Disease.

Rabbit antithymocyte globulin (ATG) has been used in allogeneic stem cell transplantation to facilitate engraftment as well as prevent graft-versus-host disease (GVHD). ATG can reduce the incidence of acute and chronic GVHD, but it prolongs the period of immunodeficiency and increases the incidence of infectious complications such as Epstein-Barr virus-related lymphoproliferative disorders (EBV-LPD). To evaluate the advantages and disadvantages of incorporating ATG into the preconditioning regimen, we reviewed records of 70 children with malignant (n=16) or non-malignant disease (n=54) who received unmanipulated bone marrow transplant (BMT) from alternative donors at our hospitals. Eleven patients (15.7%) received BMT from an HLA-mismatched related donor and 59 (84.3%) received BMT from an unrelated voluntary donor. The median age was 9 years (range, 0–21 years). The ratio of boys to girls was 2:1. The serological compatibility of HLA was as follows: 6/6 matched (n=43), 5/6 matched (n=21), 4/6 matched (n=5), and 3/6 matched (n=1). Fifty-one patients (72.9%) received a preconditioning regimen including total body irradiation, 15 (21.4%) received busulfan-based regimens, and 4 (5.7%) received other regimens. ATG (2.5mg/kg/day) was administered for 4 days (day -5, -4, -3, and -2) in all patients. For prophylaxis against GVHD, cyclosporine + methotrexate (MTX) was administered to 34 (48.6%) patients and tacrolimus + MTX to 36 (51.4%). Stable engraftment was not achieved in 2 of 70 (2.9%) patients. Both patients were rescued by second transplants from another donor. Acute GVHD (grade 2–4) developed in 13 of 68 (19.1%) evaluable patients and chronic GVHD in 16 of 62 (25.8%) evaluable patients (limited type, 4; extensive type, 12). Six patients (8.8%) suffered from interstitial pneumonitis and 5 patients (7.4%) developed EBV-LPD. Ten patients died of regimen-related toxicities and 3 died due to relapse of malignant disease. The estimate for 5-year survival from BMT was 88.5% for patients with non-malignant disease and 51.1% for patients with malignant disease. Our dose schedule of ATG appeared to be well tolerated and effective at reducing the incidence of acute and chronic GVHD in high-risk recipients.