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).

Conclusion: We 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.

Keywords: Cord blood transplantation; Hematopoietic cell transplantation; Japan; Newborn screening; Retrospective study; Severe combined immunodeficiency.

Fig. 1

Kaplan–Meier survival curves. a OS according to the period when transplanted. The subsequent analyses for OS were applied to the patients in all periods, according to b age at HCT diagnosis, c the presence of bacterial or fungal infection status at HCT, d CMV infection prior to HCT, e intensity of conditioning, f conditioning regimen, g, h SCID phenotype, and i donor type. OS, overall survival; HCT, hematopoietic cell transplantation; CMV, cytomegalovirus; RIC, reduced-intensity conditioning; MAC, myeloablative conditioning, NC, no conditioning; IS, immunosuppression; Flu, fludarabine; Bu, busulfan; Mel, melphalan; MSD, matched sibling donor; MCB, matched cord blood; mMCB, mismatched cord blood; ORD, other related donor; UBM, unrelated bone marrow

Fig. 2

Cumulative incidence of outcomes. The cumulative incidences of neutrophil recovery and platelet recovery according to (a and b, respectively) donor types and (c and d, respectively) conditioning regimens, and the cumulative incidences of e grades II–IV acute GVHD, f grades II–IV acute GVHD, g chronic GVHD, and h extensive chronic GVHD according to donor types are shown. HCT, hematopoietic cell transplantation; MSD, matched sibling donor; MCB, matched cord blood; mMCB, mismatched cord blood; ORD, other related donor; UBM, unrelated bone marrow; Flu, fludarabine; Bu, busulfan; Mel, melphalan; NC, no conditioning; IS, immunosuppression; GVHD, graft-versus-host disease