Radiotherapy-Based Conditioning Is Effective Immunosuppression for Patients Undergoing Transplantation with T-Cell Depleted Stem Cell Grafts for Severe Aplasia.

Abstract

The combination of cyclophosphamide and ALG is highly effective in inducing engraftment in patients with aplastic anaemia undergoing allogeneic stem cell transplantation. However, the incidence of graft vs. host disease remains substantial. We studied the outcome of individuals with aplastic anaemia conditioned with a radiation containing regimen followed by the infusion of stem cell grafts that had been depleted of lymphocytes with CAMPATH-1H. The conditioning regime consisted of fractionated (f) total body irradiation 8 Gy followed by f total nodal irradiation 6 Gy. Additionally, patients received cyclophosphamide 60 mg/kg on 2 consecutive days. Cytokine mobilised peripheral blood grafts from HLA identical siblings were T-cell depleted with CAMPATH-1H “in the bag”. Cyclosporin was commenced on day -1 and continued until day +90. Seventeen heavily transfused patients with aplastic anaemia with a median age of 18 years (range 14–56) were studied. Median time from diagnosis to transplantation was 172 days (range 34–443). The median CD34+ cell number infused was 3.47 x106/kg (range 1.03–18.4). All patients engrafted. Recovery was fast and patients reached 0.5 x 109/L polymorphs by median day 11 (range 9–17) days. Toxicity from the conditioning included grade 4 haematological toxicity in all. Other major toxicity was gastrointestinal mucosal damage, which exceed grade 2 in only 2 instances. 1 patient developed thrombotic thrombocytopenic purpura which responded to substitution of cyclosporin with tacrolimus and plasmapheresis. Another, who had normal blood counts died of infection on day 241. Chimerism studies at 6 months post transplantation confirmed donor origin of haematopoiesis in all 7 patients tested. None of the patients developed acute or chronic graft vs. host disease. There was no delayed graft failure and 94% of patients survive disease free, at a median of 1303.5 days (range 216–2615) from graft infusion. In this cohort of multiply transfused patients, the radiation containing schedules described in this study led to universal engraftment with limited toxicity despite T-cell depletion. No patient developed graft vs. host disease or late graft failure. Lower doses of radiation containing conditioning should be explored further.