In vivo T-cell depletion with low-dose ATG is effective in reducing cGVHD after peripheral blood stem cell myeloablative sibling transplants in CML: results from a prospective phase II study
Chronic graft versus host disease (cGVHD) incidence and severity are generally found to be greater after peripheral blood stem cell transplantation (SCT) than after bone marrow transplantation, even if few exceptions are reported, and some studies demonstrate a worse outcome due to increased mortality from GVHD, particularly the extensive type. In vivo T-cell depletion with antithymocyte globulin (ATG) is an effective strategy to decrease the incidence of GVHD. The dose and type of polyclonal antibodies are only partially defined because of wide differences in antibody specificities. GVHD prophylaxis with ATGs may include unwanted side effects such as high risk of infection and relapse. The main utilization of ATG has been for the prophylaxis of GVHD in unrelated bone marrow transplants, with clear benefit. We previously showed that low-dose (15mg/kg, total dose) ATGFresenius (F, Bad Homburg, Germany) was able to decrease the incidence of GVHD after unrelated myeloablative transplants in CML without an increase of relapse. The high anti-CTLA-4 activity present in ATGF preparation, downregulating the CD28-mediated stimulation of T cells, could partly explain the protective effect on GVHD occurrence. With regard to family donors, instead, ATG-F has been used with bone marrow, while in peripheral blood SCT, it has been almost exclusively associated with reducedintensity conditioning (RIC). No data, however, are available for myeloablative, HLAidentical sibling PBSC transplants. We prospectively planned a prospective phase II study on the use of ATG-