Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type I and III.
Shahrzad Bakhtiar, Emilia Salzmann-Manrique, Henric-Jan Blok, Dirk-Jan Eikema, Sheree Hazelaar, Mouhab Ayas, Amos Toren, Gal Goldstein, Despina Moshous, Franco Locatelli, Pietro Merli, Gerard Michel, Gülyüz Öztürk, Ansgar Schulz, Carsten Heilmann, Marianne Ifversen, Rob F Wynn, Olga Aleinikova, Yves Bertrand, Abdelghani Tbakhi, Paul Veys, Musa Karakukcu, Alphan Kupesiz, Ardeshir Ghavamzadeh, Rupert Handgretinger, Emel Unal, Antonio Perez-Martinez, Muge Gokce, Fulvio Porta, Tekin Aksu, Gülsün Karasu, Isabel Badell, Per Ljungman, Elena Skorobogatova, Akif Yesilipek, Tsila Zuckerman, Robbert R G Bredius, Polina Stepensky, Bella Shadur, Mary Slatter, Andrew R Gennery, Michael H Albert, Peter Bader, Arjan Lankester
Abstract
Type I and III leukocyte adhesion deficiencies (LADs) are primary immunodeficiency disorders resulting in early death due to infections and additional bleeding tendency in LAD-III. The curative treatment of LAD-I and LAD-III is allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective multicenter study, data were collected using the European Society for Blood and Marrow Transplantation registry; we analyzed data from 84 LAD patients from 33 centers, all receiving an allo-HSCT from 2007 to 2017. The 3-year overall survival estimate (95% confidence interval [CI]) was 83% (74-92) for the entire cohort: 84% (75-94) and 75% (50-100) for LAD-I and LAD-III, respectively. We observed cumulative incidences (95% CI) of graft failure (GF) at 3 years of 17% (9%-26%) and grade II to IV acute graft-versus-host disease (aGVHD) at 100 days of 24% (15%-34%). The estimate (95% CI) at 3 years for GF- and GVHD-II to IV-free survival as event-free survival (EFS) was 56% (46-69) for the entire cohort; 58% (46-72) and 56% (23-88) for LAD-I and LAD-III, respectively. Grade II to IV acute GVHD was a relevant risk factor for death (hazard ratio 3.6; 95% CI 1.4-9.1; P = .006). Patients' age at transplant ≥13 months, transplantation from a nonsibling donor, and any serological cytomegalovirus mismatch in donor-recipient pairs were significantly associated with severe acute GVHD and inferior EFS. The choice of busulfan- or treosulfan-based conditioning, type of GVHD prophylaxis, and serotherapy did not impact overall survival, EFS, or aGVHD. An intrinsic inflammatory component of LAD may contribute to inflammatory complications during allo-HSCT, thus providing the rationale for considering anti-inflammatory therapy pretreatment.