Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type I and III

Bakhtiar, S.; Salzmann-Manrique, E.; Blok, H.J.; Eikema, D.J.; Hazelaar, S.; Ayas, M.; Toren, A.; Goldstein, G.; Moshous, D.; Locatelli, F.; Merli, P.; Michel, G.; Ozturk, G.; Schulz, A.; Heilmann, C.; Ifversen, M.; Wynn, R.F.; Aleinikova, O.; Bertrand, Y.; Tbakhi, A.; Veys, P.; Karakukcu, M.; Kupesiz, A.; Ghavamzadeh, A.; Handgretinger, R.; Unal, E.; Perez-Martinez, A.; Gokce, M.; Porta, F.; Aksu, T.; Karasu, G.; Badell, I.; Ljungman, P.; Skorobogatova, E.; Yesilipek, A.; Zuckerman, T.; Bredius, R.R.G.; Stepensky, P.; Shadur, B.; Slatter, M.; Gennery, A.R.; Albert, M.H.; Bader, P.; Lankester, A.; Pediat Dis Working Party; Inborn Errors Working Party EBMT

doi:doi:10.1182/bloodadvances.2020002185

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...Show moreType 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.Show less

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Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type I and III