Long-Term Survival and Late Deaths After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Diseases and Inborn Errors of Metabolism.
Authors: Eapen Mary , Ahn Kwang Woo , Orchard Paul , Cowan Morton Jerome , Davies Stella M. , Fasth Anders , Hassebroek Anna , Ayas Mouhab F. , Bonfim Carmem , O'Brien Tracey , Gross Thomas , Horowitz Mary M. , Horwitz Mitchell , Horwitz Edwin M. , Kapoor Neena , Kurtzberg Joanne , Majhail Navneet S. , Ringden Olle , Szabolcs Paul , Veys Paul A. , Baker K. Scott 
Published: October 2019

Abstract
Abstract 3320
Poster Board III-208
Late mortality in children who have undergone hematopoietic stem cell transplantation (HCT) for severe combine immunodeficiency (SCID), non-SCID immune diseases and inborn errors of metabolism (IEM) has not been studied. The goals of the current analyses were to: 1) determine the probability of long-term survival after HCT in patients who survive the first 2 years after HCT; 2) identify risk factors for late deaths; and 3) determine excess mortality relative to rates in an age and sex-matched general population. Nine hundred and sixty patients with >95% donor chimerism or recovery of T-cell function who survived at least 2 years after their transplantation were included in the study. Two hundred and one patients had SCID, 407, non-SCID immune diseases and 352, IEM. Seventy percent of SCID transplant recipients received grafts from an HLA-matched sibling or mismatched relative. Fifty six percent of non-SCID and IEM transplant recipients received grafts from unrelated donors, 32% from a matched sibling and 12% from a mismatched relative. All transplantations occurred in 1980 – 2003; the median follow-up of surviving patients was 7 years. Median ages of long-term survivors were 7, 9 and 10 years for SCID, non-SCID immune diseases and IEM, respectively. Because of differences in biologic features and transplant strategies for SCID, non-SCID immune diseases and IEM, the disease groups were analyzed separately. The 7-year probabilities of overall survival were 93%, 96% and 90% for SCID, non-SCID immune diseases and IEM, respectively. No patient, disease or transplant characteristic was associated with late deaths in patients with SCID. For non-SCID immune diseases, late deaths were higher in recipients of T-cell depleted grafts (RR 4.63, p=0.003). For IEM, late deaths were higher after unrelated donor (RR 2.75, p=0.018) and mismatched related donor (RR 2.77, p=0.042) transplants compared to matched sibling donor transplant. There were 69 late deaths with 52 occurring 2 – 6 years after transplantation and 17 after 6 years. Causes of death in patients who died between 2 – 6 years included: chronic graft-versus-host disease [CGVHD] (n=12), infection including encephalitis (n=11), organ failure (n=12), post-transplant lymphoproliferative disease (n=4), primary disease (n=5), acute abdomen (n=1), status epilepticus (n=1), acute myeloid leukemia (n=1), accidental death (n=1) and not reported (n=3). Causes of death beyond 6 years included CGVHD (n=1), infection including encephalitis (n=3), organ failure (n=4), primary disease (n=2), acute abdomen (n=1), brain stem glioma (n=1) and not reported (n=5). The table below shows the estimated excess deaths per 1000 compared to an age- and sex-matched general population at 2 – 6 years and beyond 6 – 10 years after HCT. Though the risk of late deaths in this population is in excess of that for the general population for several years after transplantation, with extended follow up, the risk appears to decrease towards normal rates. Beyond 6 years after HCT, among patients transplanted for SCID and non-SCID immune diseases, the risk of mortality does not differ significantly from the general population whereas for patients with IEM, mortality rates continue to be higher than that in the general population. Screening programs aimed at identifying late complications together with planned intervention may improve long-term survival in these patients.
Excess deaths per 1000 (95% confidence interval) SCID Non-SCID IEM 2 – 6 years after HSCT 54 (28, 79)* 41 (28, 53)* 95 (82, 109)* 6 – 10 years after HSCT 25 (0, 51) 16 (0, 39) 45 (27, 62)* * Significant differences in mortality risks compared to the general population

Disclosures
No relevant conflicts of interest to declare.