Impact of Graft Function on Health Status and Quality of Life in Very Long-Term Survivors Who Received an HSCT for Inborn Errors of Immunity, a Prospective Study of the CEREDIH.

The overall survival rate after hematopoietic stem cell transplantation (HSCT) for inborn errors of immunity (IEI) has improved considerably, and its indications have broadened. As a consequence, addressing the issue of long-term health-related quality of life (HRQoL) has become crucial. Our study focuses on the health and HRQoL of post-HSCT survivors. We conducted a multicenter prospective follow-up study enrolling IEI patients who underwent transplantation in childhood before 2009. Self-reported data from the French Childhood Immune Deficiency Long-term Cohort and the 36-item Short Form questionnaires were compiled. One hundred twelve survivors were included with a median duration period from HSCT of 15 years (range 5-37), of whom 55 underwent transplantation for a combined immunodeficiency. We show that in patients evaluated at least 5 years after HSCT, 55% are still affected by a poor or very poor health status. Poor and very poor health status correlated with an abnormal graft function, defined as host or mixed chimerism, abnormal CD3+ count, or diagnosis of chronic graft-versus-host disease (poor health: odds ratio [OR] = 2.6, 95% confidence interval [CI], 1.1-5.9, P = .028; very poor health: OR = 3.6, 95% CI, 1.1-13, P = .049). Poor health was directly linked to a poorer HRQoL. Significant improvements in graft procedures have translated into better survival rates, but we show here that about half of the transplanted patients remain affected by an altered health status with a correlation to both abnormal graft function and impaired HRQoL. Additional studies are needed to confirm the impact of those improvements on long-term health status and HRQoL.

Unrelated Cord Blood Transplantation in Children, Adolescents, and Young Adults with Acute Leukemia or Myelodysplastic Syndrome: A Retrospective Comparative Study from the French Society for Bone Marrow Transplantation and Cellular Therapy Between Real-World Data and Previously Reported Results of a Randomized Clinical Trial.

We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality [TRM], engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We compared the characteristics and outcomes of RCT participants (n = 137) to a Francophone population-based registry of patients (real-world [RW] group) fulfilling the eligibility criteria used in our RCT and transplanted with 1 or 2 UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n = 141). The primary endpoint was the 2-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The 2 groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, P< .001) and to receive a radiation-free regimen (39.0% versus 60.6%, P< .001). The 2-year CI of transplantation strategy failure, TRM, and the 2-year probability of OS were similar between the 2 groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% versus 20.4% ± 6.8%, P= .01), resulting in a significantly lower disease-free survival (DFS) (59.2% ± 8.4% versus 69.3% ± 8.0%, P= .047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used.

Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia.

BACKGROUND/OBJECTIVE: The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children's irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors. DESIGN: We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI. SUBJECTS/METHODS: Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. RESULTS: Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation. CONCLUSIONS: These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.

The Impact of Donor Type on Long-Term Health Status and Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Leucémie de l'Enfant et de L'Adolescent Study.

We compared the long-term impact of donor type (sibling donor [SD] versus matched unrelated donor [MUD] or umbilical cord blood [UCB]) on late side effects and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic stem cell transplantation. We included 314 patients who underwent transplantation from 1997 to 2012 and were enrolled in the multicenter French Leucémie de l'Enfant et de L'Adolescent ("Leukemia in Children and Adolescents") cohort. More than one-third of the patients were adults at last visit; mean follow-up duration was 6.2 years. At least 1 late effect was observed in 284 of 314 patients (90.4%). The average number of adverse late effects was 2.1 ± .1, 2.4 ± .2, and 2.4 ± .2 after SD, MUD, and UCB transplantation, respectively. In a multivariate analysis, considering the SD group as the reference, we did not detect an impact of donor type for most sequelae, with the exception of increased risk of major growth failure after MUD transplantation (odds ratio [OR], 2.42) and elevated risk of osteonecrosis after UCB transplantation (OR, 4.15). The adults and children's parents reported comparable QoL among the 3 groups. Adult patient QoL scores were lower than age- and sex-matched French reference scores for almost all dimensions. We conclude that although these patients are heavily burdened by long-term complications, donor type had a very limited impact on their long-term health status and QoL.