Extended Duration of Anti-Thymocyte Globulin (ATG) Administration May Reduce the Risk of Graft-Versus-Host Disease in Patients with Aplastic Anemia Undergoing Matched-Related Allogeneic Peripheral Blood Stem Cell Transplantation

Bone marrow is the preferred stem cell source for allogeneic transplantation in the treatment of severe aplastic anemia (AA) due to a higher risk of GVHD associated with peripheral blood stem cell allografting. Higher doses or longer durations of administration of lympholytic agents such as antithymocyte globulin (ATG) or alemtuzumab may prevent GVHD and reduce graft failure rate. We treated a 19 y/o AA woman with transfusion and antibiotic dependent severe AA associated with a small PNH clone using 12/12 HLA-match allogeneic peripheral blood stem cells (allo-PBSCT) from her brother. Conditioning regimen consisted of Cyclophosphamide (CY) at 50 mg/kg/day intravenously on day -5 through day -2 before transplant. Twelve hours after each doses of CY, she was given horse ATG (Atgam; Upjohn, Kalamazoo, MI) at 30 mg/kg IV per dose infused over a period of 10 hours. ATG was given for 4 days, instead of 3 days as in the original study (R. Storb et al, Blood 1994;84:941-9). She received premedication with oral acetaminophen, intravenous diphenhydramine, and methylprednisolone at 100 mg, 30 minutes prior to each dose of ATG. During the first infusion of ATG, the patient received hydrocortisone 50 mg IV twice for infusion-related reactions, but tolerated all subsequent infusions.She received prophylaxis with acyclovir, levofloxacin, and fluconazole. Unmanipulated, G-CSF-mobilized allo-PBSCs at dose of 4.125 x 10⁶ CD34+cells/kg were transplanted fresh in 48 hours after the last dose of CY. She received GVHD prophylaxis with tacrolimus and low dose methotrexate (5 mg/kg/day) on Days +1, +3, +6, and +11. Her transplant course was notable for breakthrough vaginal spotting despite leuprolide administration, and neutropenic fever with negative infectious workup. On day +14, the patient was given a single dose of G-CSF to expedite WBC recovery. Based on CIBMTR criteria, neutrophil and platelet engraftments occurred on day +15 and day +20, respectively. She was started on steroids with a quick taper for suspected engraftment syndrome with ongoing fevers with negative cultures. She was discharged on day +16 after transplant with a total length of hospital stay of 22 days. Her outpatient course was completely uneventful with no GVHD, infection or any other transplant-related complications. The patient was never readmitted. Her blood counts remained within normal range and blood chimerism analysis showed 100% donor in myeloid and lymphoid on day+30 and day+100 evaluations. She is currently day+120 on continuous tacrolimus. This case illustrates a successful early outcome after peripheral blood allogeneic stem cell transplantation in a young patient with aplastic anemia using modified ATG protocol. The concept of T cell in vivo purging after allo-PBSCT with extended administration of ATG in aplastic anemia warrants a prospective trial.