Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study
Authors: Francesca Ferrua, Stefania Galimberti, Virginie Courteille, Mary Anne Slatter, Claire Booth, Despina Moshous, Benedicte Neven, Stephane Blanche, Marina Cavazzana, Alexandra Laberko, Anna Shcherbina, Dmitry Balashov, Elena Soncini, Fulvio Porta, Hamoud Al-Mousa, Bandar Al-Saud, Hasan Al-Dhekri, Rand Arnaout, Renata Formankova, Yves Bertrand, Andrzej Lange, Joanne Smart, Beata Wolska-Kusnierz, Victor M. Aquino, Christopher C. Dvorak, Anders Fasth, Fanny Fouyssac, Carsten Heilmann, Manfred Hoenig, Catharina Schuetz, Jadranka Kelečić, Robbert G.M. Bredius, Arjan C. Lankester, Caroline A. Lindemans, Felipe Suarez, Kathleen E. Sullivan, Michael H. Albert, Krzysztof Kałwak, Vincent Barlogis, Monica Bhatia, Victoria Bordon, Wojciech Czogala, Laura Alonso, Figen Dogu, Jolanta Gozdzik, Aydan Ikinciogullari, Gergely Kriván, Per Ljungman, Isabelle Meyts, Peter Mustillo, Angela R. Smith, Carsten Speckmann, Mikael Sundin, Steven John Keogh, Peter John Shaw, Jaap Jan Boelens, Ansgar S. Schulz, Petr Sedlacek, Paul Veys, Nizar Mahlaoui, Ales Janda, E. Graham Davies, Alain Fischer, Morton J. Cowan, Andrew Richard Gennery
Journal: Journal of Allergy and Clinical Immunology (2019)

CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT).We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics.We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure.Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow-derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%.HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy.