MISMATCHED BONE-MARROW TRANSPLANTATION FOR OMENN SYNDROME - A VARIANTOF SEVERE COMBINED IMMUNODEFICIENCY

Omenn syndrome is a variant of SCID, inherited as an autosomal recessi ve disorder, and characterized by severe eczematoid dermatitis, eosino philia, elevated serum IgE and a distinctive histology in enlarged lym ph nodes, The etiology of Omenn syndrome is unknown, however, unlike o ther forms of SCID; patients with Omenn syndrome have activated T lymp hocytes in their circulation capable of non-MHC restricted cytotoxic f unction, Recently, it has been observed that the use of immunosuppress ive therapy, particularly cyclosporine, can modify the clinical manife stations of the disorder, Prior to the use of bone marrow transplantat ion this disease was universally fatal, Death typically occurred in in fancy as the result of opportunistic infections and/or malignancies, m ost notably lymphomas. While bone marrow transplantation has become qu ite successful for many phenotypes of SCID, even with the use of alter native donors other than histocompatible siblings, in Omenn syndrome i t remains a challenge. In our experience, patients with Omenn syndrome exhibit a higher incidence of Gram negative sepsis, before and during transplantation, and carry a significant risk of post-transplant reje ction when compared with patients with other phenotypes of SCID. We re port the results of six patients treated with bone marrow transplantat ion from alternative donors, three had unrelated donors (URD) and thre e had haplo-identical parental donors. Five of the six patients achiev ed complete and/or durable donor cell engraftment and only one patient experienced acute GVHD. Three patients died of transplant-related com plications (infection or EBV-associated B cell lymphoma) between day 22 and day +95 post-transplant, Three patients survived more than 1 ye ar post-transplant, However, two of the three eventually died from inf ections secondary to autologous recovery or chronic extensive GVHD. On e patient is alive and has demonstrable correction of her underlying i mmunologic deficit 36 months post-BMT.