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.

Bakhtiar, S., Salzmann-Manrique, E., Blok, H. -., Eikema, D. -., 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., Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type I and III, <<BLOOD ADVANCES>>, 2021; 5 (1): 262-273. [doi:10.1182/bloodadvances.2020002185] [https://hdl.handle.net/10807/228792]

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

Locatelli, Franco
Writing – Review & Editing
;
2021

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 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.
2021
Inglese
Bakhtiar, S., Salzmann-Manrique, E., Blok, H. -., Eikema, D. -., 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., Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type I and III, <<BLOOD ADVANCES>>, 2021; 5 (1): 262-273. [doi:10.1182/bloodadvances.2020002185] [https://hdl.handle.net/10807/228792]
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