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

2021

BLOOD ADVANCES

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

01 Pubblicazione su rivista

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.

DOI: 10.1182/bloodadvances.2020002185

ISSN: 2473-9529

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 5.006). 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.