A Comparison of Acute GVHD after HLA-Haploidentical and HLA-Identical Stem Cell Transplantation.

Acute graft-versus-host disease (aGVHD) is a major obstacle of allogeneic stem cell transplantation (SCT). We compared a cohort of 58 patients with HLA-haploidentical transplants (haplo) and a contemporary group of 229 patients with HLA-identical transplants (id) for the manifestation of aGVHD. Haplo-patients were given unmodified marrow (bm) and CD6- depleted mobilized blood cells (mbc) 6 days after marrow transplantation. The combination of cyclosporin A (CSA) and a short course of methotrexate (sMTX) was given post-grafting. Standard intensity conditioning was given to 34 and reduced intensity conditioning to 24 patients. Id-patients were given bm in 140, mbc in 79 and the combination of bm and mbc in 6 cases. Post grafting immunosuppression consisted of CSA either alone (N=10) or in combination with sMTX (N=158), and/or mycophenolate mofetil (MMF) (N=57). Conditioning was of reduced intensity in 50 patients and standard in 175 patients. Haplo-patients were younger in age (34 vs. 44 yrs.), more frequently male and in a more advanced stage of their disease. Manifestations of aGVHD, microangiopathy characterized by schistocytes and elevated LDH and virus infections were evaluated. Haplo-patients had more severe aGVHD of the skin than id-patients (IBMTR index B – D: 53% vs. 37%; p<0.02). Response to the treatment with corticosteroids was better in haplo-patients than in id-patients (74% vs. 52%; p =0.048). Extensive chronic GVHD was less frequent in haplo-patients than id-patients (14% vs. 39%; p=0.005). However virus infections requiring virostatic therapy were more frequent in haplo-patients (60% vs. 40%; p=0.03). Modification of aGVHD has been achieved by transfusion of CD6-depleted mbc 6 days after transplantation of unmodified bm. CD6-depleted mbc contain non-specific suppressor cells. Improved depletion has eliminated severe aGVHD (IBMTR C & D) completely. However immune deficiency and recurrent viral infections remain a problem.