Leukocyte Adhesion Deficiency Type I: The Outcome of Reduced- Intensity Conditioning Hematopoietic Stem Cell Transplantation

Introduction:Leukocyte adhesion deficiency type I(LAD-I) is a congenital disorder that is usually fetal during first decade of life due to recurrent life-treating bacterial infection. Allogeneic hematopoietic stem cell transplantation (HSCT) has been accepted as one of the only curative treatment for LAD-I. The conditioning regimen used for HSCT in LAD-I is still controversial issue.

Patients and Methods:  Between 2007 and 2014, 20 pediatric patients(12 female) with confirmed LAD-I who were referred to our center underwent HSCT. The median age at the time of diagnosis and transplantation was 11.5 months (range:1month-5years) and 24.5 months (range:4months-14years), respectively. Patients underwent HSCT from matched related donor (n=15), mismatched related or unrelated donor(n=3), unrelated fully matched donor(n=1) and haploidentical relative donor(n=1). Sources of stem cells were peripheral blood(n=10), bone marrow(n=8) and cord blood(n=2). All patients were admitted several times due to infection, prior to HSCT. The study utilized reduced-intensity conditioning(RIC) regimen consisting of Fludarabine, Melphalan and ATG. Cyclosporine and Methylprednisolone were used as graft-versus-host disease (GvHD) prophylaxis regimen.

Result: All but one patient engrafted. The median time for ANC and platelet engraftment was 12 days (range: 10-23days) and 15 days (range: 10-32days), respectively. With a median follow- up of 43 months (range: 6-85month), 7 patients showed acute GvHD (2 grade I-II, 5 grade III-IV), while 2 patients developed limited chronic GvHD. The 4-year OS and DFS was 80% (95%CI: 54-92%). Among 19 patients who showed engraftment, 9 with full chimerism and 7 with mixed chimerism are still alive and disease free. Five patients expired due to GvHD and infection.

Conclusion: As pre-transplant infections in LAD-I lead to rise in mortality rate, the use of myeloablative conditioning regimen may result in increased risk of mortality. Using less-toxic regimen with RIC seems to be highly effective and will improve manifestation of LAD-I with either full or mixed chimerism.