Stem Cell Transplantation and Long-Term Survival for Primary Immunodeficiencies: Outcomes Among the Donor Sources and Different Diagnostic Groups

Matched related hemopoietic stem cell transplantation (MRD-HSCT) for patients with Primary Immunodeficiencies (PIDs) has been life saving. There is less information regarding stem cell transplantation from unrelated donors including umbilical cord blood units. We report the outcome following HSCT (1998-2012) in 69 patients with PIDs: SCID (n=35), WAS (n=9), Phagocytic disorders (CGD (n=17), LAD (n=4)); and other (n=4; one each; Interferon γ receptor deficiency, Hyper IgM syndrome, Autosomal recessive Hyper IgE syndrome (Dock 8 mutation), and reticular dysgenesis).  The median age at transplant was 1 year (range, 0.1-17 years). Twenty patients received an MRD graft, 22 patients received a matched unrelated donor graft (MUD), 4 patients received a mismatched unrelated donor graft, 15 patients received a haploidentical related donor graft and 9 patients received a mismatched unrelated cord blood unit (MMUCB). One patient received a MMUCB after a haploidentical graft failure. 58 patients received ablative conditioning regimen with busulfan, cyclophosphamide, and fludarabine or cytarabine. Six patients received reduced intensity conditioning using fludarabine with anti-CD52 or/and anti-CD45. Six SCID patients were not conditioned. 52 patients received anti-CD52; no serotherapy was given for MMUCB grafts. Graft versus host disease (GvHD) prophylaxis combined cyclosporine and methotrexate or cyclosporine and prednisone except for MUCB recipients who were given cyclosporine and MMF as prophylaxis. Engraftment: Forty five of 67 evaluable patients (65%) achieved full donor chimerism (>90%) of all cell lineages including T cells. Twelve patients had primary graft failure. 10 were haploidentical grafts and 2 were MUD grafts. All except one were rescued with a repeat stem cell infusion. Just 3/67 patients developed grade II-IV aGvHD and no patient developed chronic GvHD. Survival. With a median follow up of 4 years (range, 0.3-12 years), overall survival was: 95% and 86%, for phagocytic disorders and SCIDs respectively; and 77% and 75% for WAS and other diseases, respectively. Recipients of MRD and UCB had 100% survival: MUD graft recipients had an 88% survival, while recipients of mismatched unrelated or haploidentical related transplants, had 50% and 71% survival respectively. Infection was the commonest cause of death.  Hence excellent overall survival for PID patients may be obtained after unrelated HSCT and results using matched related grafts and mismatched cord blood units are highly comparable.