Long Term Psycho-Social Aspects and Risk Factors for Severe Infections, Ocular, Pulmonary, Bone, Thyroid and Other Complications after Allogeneic Hematopoietic Stem Cell Transplantation for Children with Hematologic Malignancies.
Authors: Ferry Christèle , Gemayel Gladys , Rocha Vanderson , Labopin Myriam , Esperou Hélène , Robin Marie , de Latour Régis Peffault , Ribaud Patricia , Devergie Agnès , Gluckman Eliane , Socie Gerard 
Published: October 2019

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with hematologic malignancies. However, many long term complications are observed with a longer follow-up. Few data is available analyzing psycho-social aspects and risk factors of various long term complications in a same cohort of children. We have reviewed the charts of 112 children younger than 16 years, transplanted for hematologic malignancies between 1985 and 2000 at Saint Louis Hospital, and who survived at least 1 year after transplant. Landmark analysis and cumulative incidence using death and relapse as competing events were used to calculate incidences of complications after one year of HSCT. Univariate analysis used the Fine and Gray test and multivariate Cox model was used with chronic GVHD (cGVHD) as time dependent variable. Results: Median age at transplant was 8.3 years (0.73–15 years), median follow-up from 1 year after transplantation was 8 years (0.3–16.5). Most frequently, children had acute leukemia (n=101, 90%) and 92 patients were transplanted with an HLA-identical sibling donor.Total body irradiation (TBI) was used in 87 patients as part of conditioning regimen and fractionated TBI was used since march 1994 in 37 patients. At 10 years, overall survival was 75±5%, transplant related mortality (TRM) was 18%±4 and relapse 14±3%. Ten year cumulative incidence of severe infections (mostly bacterial) was 31%±4 (n=33); it was 44±4% for cataract (n=48); 20±4% for pulmonary dysfunction (mostly restrictive abnormalities) (n=20); 29±5% for osteoarticular complications (mostly osteonecrosis) (n=27); 36±4% for hypothyroidism (n=36); 11±3% for cardiac complications and 7±3% for secondary malignancies (n=8). The number of complications per patient increased with time, from 1 at a median observation time of 73 months to 3 at a median of 120 months. Factors related to patient, disease, donor and transplant characteristics were analyzed in univariate and multivariate analysis for complications with at least 20 events. There was a trend of higher risk of TRM (p=0.06), osteoarticular complications (p=0.09) and infections (p=0.07) for patients presenting cGVHD. cGVHD was significantly associated with higher risk of pulmonary dysfunction (p=0.02). However, single dose TBI (sTBI) or only TBI was the most important factor among other factors that increased the risk of cataract (p<0.001), pulmonary (p=0.004), osteoarticular (p=0.04) and thyroid complications (p<0.0001).Concerning psychological health and social issues; half of the patients had psychological disturbance, 13 patients had signs of depression, 16 history of eating behavior disorders. Half of the patients who had more than 18 years had an employment, 36 patients achieved normal scholarship, 69 had scholar difficulties and 12 patients achieved superior level studies. In conclusion with a longer follow-up in survivors of HSCT long term complications become an important issue. These complications reached no plateau even after 10 years. Development of less toxic conditioning regimen, avoid sTBI and probably better control of cGVHD may prevent late effects and improve quality of life of long term survivors.