Second allogeneic stem cell transplantation was realized in 48 patients with myeloid and lymphoid neoplasms at Gustave Roussy institute since 1987. Overall survival rate was about 30 % with better outcome in acute myeloid leukemia cases. Non-relapse related mortality is overwhelming, especially in myelodysplasia patients and despite the fact that complete remission was obtained in their majority. Graft versus Host disease is very common after second transplantation with many grade III – IV cases and one death from severe pulmonary GvHD lesions. Reduced intensity conditioning is certainly less toxic and together with optimal GvHD and infectious disease management, Second SCT may be a reasonable therapeutic option and the only curative treatment for many hematological malignancies.