Hematopoietic Cell Transplantation for Severe Combined Immunodeficiency Patients: a Japanese Retrospective Study

Abstract

Purpose Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. Methods A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974-2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). Results The 10-year overall survival (OS) of the patients who received HCT in 2006-2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006-2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). ConclusionWe showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID.

Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study

“…Transfusion of RBCs had emerged as a potential risk factor for hospital-acquired infections in various clinical settings, including sepsis ( Dupuis et al., 2017 ; Dupuis et al., 2017 ; Nederpelt et al., 2020 ). In addition, it is associated with an increased risk of venous thrombosis with allogeneic transfusion and transfusion-related infections ( Jaffray et al., 2020 ; Miyamoto et al., 2021 ). Furthermore, stored RBCs and platelets can release intracellular cytokines and other components that induce an immunosuppressive phenotype in antigen-presenting cells and lymphocytes ( Aslam et al., 2008 ; Torrance et al., 2015 ).…”

Endocrinopathies in Inborn Errors of Immunity

“…Most IEI are due to defects in genes that are essential for hematopoietic cells to function normally, and supportive therapies, such as immunoglobulin G (IgG) infusions and antibiotics, are occasionally unsatisfactory for long-term outcomes. The only curative approach is the replacement of impaired cells by healthy donor hematopoietic stem cells and allogeneic HCT (allo HCT) (108)(109)(110). One of the clinical implications of HCT is the long-term complications that cause chronic and irreversible damage to various organs (111), including the endocrine glands.…”

“…Another issue for reproduction in IEI patients is age at HCT. Most patients with IEI receive HCT before the reproductive age ( 108 , 112 ), resulting in limited options for the preservation of fertility before HCT, such as cryopreservation of gonadal tissues. However, at present, cryopreservation of gonadal tissues is considered an experimental technique, and this procedure may only be utilized for carefully selected patients as an experimental protocol ( 117 ).…”

Population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency undergoing hematopoietic stem cell transplantation

“…Severe combined immunodeficiency (SCID), whose estimated incidence of the disease was 1/58,000 (Kwan et al, 2014;Bayram et al, 2021), was an inborn error of immunity characterized by the severe dysfunction of cellular and humoral immunity owing to impaired T cell and B cell development or function (Picard et al, 2018;Miyamoto et al, 2021). This situation caused serious consequences, and affected children, who were born with marked susceptibility to pathogens, could not be managed or controlled at last (Chinn and Shearer, 2015).…”

“…Since 1968, hematopoietic stem cell transplantation (HSCT) had been used to treat patients with SCID (Gatti et al, 1968;Miyamoto et al, 2021). For most forms of SCID, HSCT was the only curative therapy (Bayram et al, 2021).…”