Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries

Abstract

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.

Meta‐analysis of hematopoietic stem cell transplantation in major histocompatibility complex class II deficiency

“…The median age to transplant was 18 months, similar to other reports in the literature of HSCT in PID 9,10 . In this analysis, we did not find differences in patients who underwent HSCT before 12 months of age, previous studies in the field showed better survival when it was performed before 2 years of age, 4 either way, HSCT should be considered as soon as the diagnosis is made, since previous infections or organ damage can affect survival during the procedure.…”

“…We found no apparent benefit of combining 2 or more groups of medication for GVHD prophylaxis. As observed in our analysis, other studies also found no significant differences in GVHD according to donor type 9,26 …”

“…Hematopoietic stem cells can be found in the bone marrow, peripheral blood, and umbilical cord obtained at the time of delivery. The most frequent source for stem cells in patients with MHC II deficiency was bone marrow, but the number of HSCT using UCB as a source of hematopoietic stem cells has increased in recent years 9,15 . UCB offers certain advantages such as easier procurement, lack of inconvenience for the donor, and the great number of UCB banks, all of which entails faster availability for the patient 16,17 .…”

“…Overall survival for patients with MHC II deficiency after HSCT is lower than in other forms of PID 3,4,9,13,29 . Pai et al described a better survival rate for patients that underwent transplant before 3.5 months of age 26 ; in the cases, we analyzed only one‐third of the patients who underwent transplantation before 1 year of age, with only 2 patients under 3.5 months.…”

Gene therapy for severe combined immunodeficiencies and beyond

“…One possible explanation is that after haploidentical HSCT, subclinical graft versus host disease partially impairs thymus function. Nevertheless, recent advances in haploidentical HSCT (i.e., TCR αβ depletion, or even T cell–replete HSCT followed by the suppression of allogeneic T cells via in vivo cyclophosphamide treatment; Bertaina et al, 2014; Fernandes et al, 2018) may challenge this conclusion.…”