OBJECTIVE: X-linked hyper-immunoglobulin M (X-HIM) syndrome is a rare genetic immunodeficiency syndrome caused by mutations in the gene encoding CD40 ligand (CD40L, CD154). Allogeneic hematopoietic stem cell transplantation (HSCT) offers the prospect of immune reconstitution in X-HIM syndrome. Standard HSCT using high-dose chemoradiotherapy can be followed by serious hepatic problems, including veno-occlusive disease, graft-versus-host disease, and/or drug-induced hepatotoxicity. In patients whose liver function is compromised before HSCT, such as in X-HIM syndrome caused by cholangiopathy and hepatitis related to opportunistic infections, there is a higher likelihood of hepatotoxicity. We explored nonmyeloablative HSCT in 2 patients with X-HIM syndrome. Nonmyeloablative HSCT without liver transplant for X-HIM syndrome, to our knowledge, has not been described previously. METHODS: Two children with X-HIM syndrome and persistent infections had documented cholangiopathy on liver biopsy. Both children underwent nonmyeloablative HSCT from HLA-matched siblings with fludarabine, busulfan, and anti-thymocyte globulin as their preparative regimen. Graft-versus-host disease prophylaxis consisted of cyclosporine. RESULTS: Both children are >2 years after their HSCT. One remains a mixed chimera, and the other shows 100% donor chimerism. Both children are now free of infections and are no longer dependent on intravenous gammaglobulin. Both show response to immunizations. Both have had resolution of their cholangiopathy. CONCLUSIONS: Nonmyeloablative HSCT from HLA-matched siblings can offer immune reconstitution without hepatotoxicity in patients with X-HIM syndrome and preexisting cholangiopathy. Even with stable mixed chimerism after allogeneic HSCT, patients may be able to enjoy a normal phenotype. Nonmyeloablative HSCT warrants additional study in X-HIM syndrome.
OBJECTIVE:X-linked hyper-immunoglobulin M (X-HIM) syndrome is a rare genetic immunodeficiency syndrome caused by mutations in the gene encoding CD40 ligand (CD40L, CD154). Allogeneic hematopoietic stem cell transplantation (HSCT) offers the prospect of immune reconstitution in X-HIM syndrome. Standard HSCT using high-dose chemoradiotherapy can be followed by serious hepatic problems, including veno-occlusive disease, graft-versus-host disease, and/or drug-induced hepatotoxicity. In patients whose liver function is compromised before HSCT, such as in X-HIM syndrome caused by cholangiopathy and hepatitis related to opportunistic infections, there is a higher likelihood of hepatotoxicity. We explored nonmyeloablative HSCT in 2 patients with X-HIM syndrome. Nonmyeloablative HSCT without liver transplant for X-HIM syndrome, to our knowledge, has not been described previously. METHODS: Two children with X-HIM syndrome and persistent infections had documented cholangiopathy on liver biopsy. Both children underwent nonmyeloablative HSCT from HLA-matched siblings with fludarabine, busulfan, and anti-thymocyte globulin as their preparative regimen. Graft-versus-host disease prophylaxis consisted of cyclosporine. RESULTS: Both children are >2 years after their HSCT. One remains a mixed chimera, and the other shows 100% donor chimerism. Both children are now free of infections and are no longer dependent on intravenous gammaglobulin. Both show response to immunizations. Both have had resolution of their cholangiopathy. CONCLUSIONS: Nonmyeloablative HSCT from HLA-matched siblings can offer immune reconstitution without hepatotoxicity in patients with X-HIM syndrome and preexisting cholangiopathy. Even with stable mixed chimerism after allogeneic HSCT, patients may be able to enjoy a normal phenotype. Nonmyeloablative HSCT warrants additional study in X-HIM syndrome.
Authors: M Teresa de la Morena; David Leonard; Troy R Torgerson; Otavio Cabral-Marques; Mary Slatter; Asghar Aghamohammadi; Sharat Chandra; Luis Murguia-Favela; Francisco A Bonilla; Maria Kanariou; Rongras Damrongwatanasuk; Caroline Y Kuo; Christopher C Dvorak; Isabelle Meyts; Karin Chen; Lisa Kobrynski; Neena Kapoor; Darko Richter; Daniela DiGiovanni; Fatima Dhalla; Evangelia Farmaki; Carsten Speckmann; Teresa Español; Anna Shcherbina; Imelda Celine Hanson; Jiri Litzman; John M Routes; Melanie Wong; Ramsay Fuleihan; Suranjith L Seneviratne; Trudy N Small; Ales Janda; Liliana Bezrodnik; Reinhard Seger; Andrea Gomez Raccio; J David M Edgar; Janet Chou; Jordan K Abbott; Joris van Montfrans; Luis Ignacio González-Granado; Nancy Bunin; Necil Kutukculer; Paul Gray; Gisela Seminario; Srdjan Pasic; Victor Aquino; Christian Wysocki; Hassan Abolhassani; Morna Dorsey; Charlotte Cunningham-Rundles; Alan P Knutsen; John Sleasman; Beatriz Tavares Costa Carvalho; Antonio Condino-Neto; Eyal Grunebaum; Helen Chapel; Hans D Ochs; Alexandra Filipovich; Mort Cowan; Andrew Gennery; Andrew Cant; Luigi D Notarangelo; Chaim M Roifman Journal: J Allergy Clin Immunol Date: 2016-09-30 Impact factor: 10.793
Authors: John Routes; Mario Abinun; Waleed Al-Herz; Jacinta Bustamante; Antonio Condino-Neto; Maria Teresa De La Morena; Amos Etzioni; Eleonora Gambineri; Elie Haddad; Lisa Kobrynski; Francoise Le Deist; Shigeaki Nonoyama; Joao Bosco Oliveira; Elena Perez; Capucine Picard; Nima Rezaei; John Sleasman; Kathleen E Sullivan; Troy Torgerson Journal: J Clin Immunol Date: 2014-03-12 Impact factor: 8.542