Unrelated Umbilical Cord Blood Transplantation for Patients with Primary Immunodeficiency: A Report From the Registry of the Japan Cord Blood Bank Network

Umbilical cord blood (UCB) has been increasingly used as a hematopoietic stem cell (HSC) source for patients with primary immunodeficiency (PID) with varying degree of success; however, the information on outcome of UCB transplantation (UCBT) for these patients is still limited. We report here the results of unrelated UCBT carried out for 88 PID patients between 1998 and 2008, consecutively registered on the Japan Cord Blood Bank Network (JCBBN)

JCBBN is a national unrelated UCB bank network supported by the Ministry of Health, Labor, and Welfare of Japan, and currently 11 regional UCB banks are affiliated. The registry of JCBBN collects recipients' clinical information at 100 days post transplantation, and further recipients' information on survival, disease status, and long-term complications are annually renewed by follow-up forms. Of the 88 PID patients registered, 39 were severe combined immunodeficiency (SCID), 23 were Wiskott-Aldrich syndrome (WAS), 7 were chronic granulomatous disease (CGD), 5 were severe congenital neutropenia (SCN), and 14 were other primary immunodeficiencies. The analysis on engraftment, survival, incidence of graft-versus-host disease (GVHD), and finally, risk factors for overall mortality were carried out in the present study.

Sixty-seven patients (76%) achieved stable engraftment. The cumulative incidence of neutrophil recovery at day 100 post-transplant was 77% (95% confidence interval [CI], 66% - 85%), and no statistical difference was observed among the disease groups (SCID vs. WAS vs. others, P = 0.21) and the conditioning types (myeloablative conditioning [MAC] vs. reduced intensity conditioning [RIC], P = 0.80). Twenty-nine out of 88 patients were fully-matched for HLA-A, -B, and -DRB1, while 59 received HLA-mismatched transplantation. The cumulative incidence of grade 2 – 4 acute GVHD at day 100 was 28% (95%CI, 19% - 38%), and the incidence was higher in WAS patients compared to non-WAS patients (P = 0.02). There was a trend for higher incidence of grade 2 – 4 acute GVHD in ≥2 HLA-antigens mismatched UCBT, however, not statistically significant (P = 0.071). Chronic GVHD was observed in 9 recipients, and its cumulative incidence at day 180 was 13% (95%CI, 7% - 23%). Sixty-two PID recipients were alive at last-follow-up, and 5-year overall survival rate (5Y-OS) for all 88 patients was 69% (95% CI, 64% - 74%). 5Y-OS for SCID and WAS were 71% and 82%, respectively. The main cause of death before day 100 post-transplant was infection (17/19), while that after day 100 was GVHD (5/7). Eight patients with previous history of HSC transplantation were excluded in the further risk factor analysis. Pre-transplant infections, no conditioning, ≥2 HLA-antigen mismatched UCB donor, and diagnosis other than SCID/WAS/SCN were associated with poor prognosis, and all these remained as significant poor prognostic factors in multivariate analysis. In addition, UCBT with RIC was associated with good prognosis (P = 0.011).

We conclude that unrelated UCB can be considered as a candidate HSC source for PID patients who do not have an HLA-matched sibling donor. Control of pre-transplant infection and selection of HLA-matched donor will lead to a better outcome. UCBT with RIC might benefit for PID patients, however, prospective evaluation is needed.

No relevant conflicts of interest to declare.