Patients and HSCT characteristics
Among the cohort of 1018 participants included in the FCILSG, 112 responded to the inclusion criteria (supplementary Figure E1). Main characteristics of diseases and transplants are given in Table 2. Most frequent underlying IEI was combined immune deficiency (CID) (49%) (including 30% of SCID), CID with syndromic features (18%), phagocytic disorder (12%), and IEI with dysregulation (21%). Details of IEI diagnosis are available in supplementary Table E2. Median age at HSCT was 1 year old (range 0.1-17), transplantations were performed between 1976 and 2009. Overall, these 112 patients received 128 transplants, 16 receiving a second transplantation after graft failure. 55% of the patients were transplanted after 2000. Median follow-up after transplant was 15 years (range 5-37). The median age at study participation was 17-year-old (6-40), with 52 adults, 19 teenagers aged 11 to 17 years and 41 younger children.
Health needs in the year prior to study entry
Health needs in the last 12 months before study entry were prospectively assessed to better capture the daily impact for the patients of their health status (Table 3). Eighteen percent of the patients (n= 19) had been hospitalized, including 7 for infections and 2 for malignancies. Thirty six percent (n=40) needed antibiotics in the previous year, either orally or intravenously. Twelve percent (n=14) were on immunoglobulins replacement therapy, 21% (n= 24) received an antimicrobial prophylaxis. Respiratory therapy, hormonal substitution or painkillers (at least mild opioids) were needed in 17%, 14% and 21% of the patients respectively.
Three levels of health status were established in order to reflect the impact of cumulative health needs during the last 12 months preceding the completion of the questionnaire (Table 1). They were established based on clinical insight and confirmed as statistically relevant through a confirmatory factor analysis (RMSEA: 0,076, CFI:0,875, TLI:0,840, SRMR:1,081). Fifty patients (45%) presented a level 1 health status. Combined level 2 and 3 accounted for 62 patients (55%) with 39 level 2 (35%) with a poor health and 23 level 3 (20%) with a very poor health (Table 3).
Immunological outcome
Acute and chronic Graft Versus Host Disease (GVHD) was noticed in 40% (45 patients) and 14% (16 patients) respectively. Chronic GVHD was limited in all excepted one patient and was always preceded by aGvHD. Whole blood chimerism at last follow-up (median time from HSCT of 7 years (± 8 years)) was donor in 62% of the patients, mixed for 28% while 4% of the patients presented with host chimerism. CD3+ lymphocytes count at last follow up was found normal according to age in 63% (71 pts). Based on the criteria we proposed to define a normal graft function, they were met in 40 patients (36%) of the cohort.
Factors associated with health status
We used univariate and multivariate analysis to search for factors associated with the occurrence of Level 2 and/or 3 health status (Table 4).
In univariate analysis, diagnosis (SCID versus non-SCID), gender and donor origin were not statistically linked to health status. Older age at time of HSCT and older age at study entry were statistically linked to a poor and very poor health.
In uni- and multivariate analysis an abnormal graft function was statistically associated with a poor and/or very poor health (OR 2,9 CI 95%: 1,2-6,6, p:0,014; OR 2,6 CI 95%: 1,1-5,9 p:0,028) and with a very poor health (OR 4,5 CI 95%: 1,3-15, p:0,016; OR 3,6 CI 95%: 1,1-13, p:0,049).
Health Related Quality of life
As a majority of level 3 patients were adults (18/23), we analyzed the HRQoL only in adult survivors. Overall, there was a significant deterioration of quality of life from level 1 through level 3 health status, for physical as well for mental and social domains. All effect sizes were either medium or large. As reported in table 5, adult survivors with a poor health (level 2) declared a significantly worse HRQoL especially for the subscale general health and the composite physical score. Strikingly, patients with a very poor health (Level 3) had a significantly worse HRQoL than patients with a good health (Level 1) with all the domains, both physical and mental, impacted. Mental and physical composite scores proved significantly lower compared to level 1 patients’ QoL (p<0,05). Interestingly, both patients with poor and very poor health declared the starkest difference on the global health subscale with the largest effect size, respectively 1,55 and 2,59.