Spectrum of Infections with a Protocol of Dual T-Lymphocyte Suppression Using ATG and PTCy for Gvhd Prophylaxis in Allogeneic Transplants for High-Risk Hematological Malignancies

Abstract

Introduction ATG and PTCy have been individually shown to reduce rates of GVHD in allogeneic transplants. We adopted a combination regimen of ATG and PT-Cy for GVHD prophylaxis in allogenic transplants for high risk hematological malignancies in our centre, to decrease the rates of acute and chronic GVHD. Objectives We analysed the spectrum of infections in patients who received this dual T lymphocyte suppression protocol. Patients and methods Reduced intensity conditioning consisted of iv Fludarabine, iv Busulphan, and low dose TBI. GVHD prophylaxis was with Thymoglobulin 4.5mg/kg total dose, PT-Cy 100 mg/kg total dose and cyclosporine. The stem cell source was G-CSF stimulated PBSCs. Results 197 patients (median age 57 y, range 19-74y) with high-risk hematological malignancies were treated with this protocol. The donor types were as follows-10/10 matched unrelated donor (MUD) in 76, 9/10 mismatched unrelated (MMUD) in 26, 10/10 matched related donor(MRD) in 43 and haplo-identical (HI) donors in 52 patients. The median follow-up in the entire cohort was 12 months. The 1year OS in the MUD, MMUD, MRD and HI groups were 75%, 50%, 63.3% and 56.7% respectively. The overall percentages of proven bacterial, viral, and fungal infections were 49%, 62% and 11% respectively (Table 1). The overall incidence of CMV reactivation was 48% and was significantly different among the 4 donor groups (p=0.00). We also observed high rates of EBV reactivation (33%) and BK cystitis (18%). There were 14 pathologically confirmed cases of post-transplant lympho-proliferative disorder (PTLD), of which 1 responded to discontinuation of immune-suppression and the rest needed treatment with Rituximab. There was one death attributed to PTLD. Infections were the primary cause of death in 18 patients (23% of deaths) and a contributory cause of death in an additional 16 patients (20% deaths). The overall incidence of grade 3-4 acute GVHD in our patients was 10.1 % and of moderate/severe NIH stage chronic GVHD was 11.6% which is low compared to conventional GVHD prophylaxis regimes. Only 10% of deaths were attributable to GVHD. Conclusion Our experience shows that dual T lymphocyte suppression with PT-Cy and ATG for GVHD prophylaxis results in low rates of acute and chronic GVHD, but is associated with high rates of infections, especially viral reactivation and PTLD.