LMP7 polymorphism may modify the presentation and clinical impact of minor histocompatibility antigens in matched related hematopoietic stem cell transplantation.

Differential expression of minor histocompatibility antigens between the recipient and donor determines their disparity and can be modified by immunoproteasomes that regulate their processing and presentation. We examined the impact of HA-1 and HA-8 disparity, and immunoproteasome LMP7 polymorphism in 130 pairs. In multivariate analysis, HA-1 disparity showed a statistically significant association with an increased incidence of acute graft-versus-host disease (aGVHD) II-IV (p = 0.043, HR: 3.71, 95%CI = 1.04-13.26), while LMP7-Q/Q showed a trend toward increased incidence of aGVHD compared to LMP7-Q/K and K/K genotypes (p = 0.087, HR: 2.36, 95%CI = 0.88-6.31). All HA-1 and HA-8 disparate patients who developed aGVHD had the LMP7-Q/Q genotype. No significant association could be detected between HA-1, HA-8, or LMP7 and chronic GVHD, relapse-free survival (RFS), overall survival (OS), or transplant-related mortality (TRM). In conclusion, we suggested an association between the HA-1 disparity and the risk of developing aGVHD with a possible modifying effect of LMP7.

The Use of Post-transplantation Cyclophosphamide in Peripheral Blood HLA-matched Stem Cell Transplantation as Graft-versus-host Disease Prophylaxis in Patients With Malignant or Non-malignant Hematologic Disorders: A Single-center Experience of 52 Patients.

INTRODUCTION: Studies addressing the utilization of post-transplant cyclophosphamide (CY) as graft-versus-host disease (GVHD) prophylaxis in allogeneic hemopoietic stem cell transplantation from matched sibling donors are limited and with controversial results. Chronic GVHD incidence necessitating systemic treatment is around 35% in peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen-matched sibling donors. PATIENTS AND METHODS: In this study, high-dose CY was added to PBSCT aiming to reduce the incidence of GVHD to reach a lower figure compared with standard GVHD prophylaxis. Fifty-two patients with either benign or malignant hematologic disorders who underwent stem cell transplantation at Nasser Institute Hospital in Egypt from November 2017 to October 2018 were enrolled in this study. Fifty patients had fully human leukocyte antigen-matched siblings, whereas the remaining 2 patients had 1 locus class I mismatched donors. Pre-transplant conditioning regimen was fludarabine and busulfan (FLU/BU) in malignant cases (73.1%) and FLU/CY in benign hematologic disorders (26.9%) and 1 patient with hypocellular myelodysplastic syndrome. For GVHD prophylaxis, CY was given at a dose of 50 mg/kg/day on days 3 and 4 post-transplantation, and cyclosporine (CSA) starting day 5 in 96.1% of patients. For the 1-locus mismatched patients, both CSA and mycophenolate mofetil were administered starting day 5. RESULTS: The 1-year incidence of acute GVHD (aGVHD) was 15.3% and for chronic GVHD (cGVHD) was 13.4%. Historical data of GVHD prophylaxis at our center using CSA and methotrexate showed an incidence of 37% for aGVHD and 33.9% for cGVHD. CONCLUSIONS: Post-transplant CY GVHD prophylaxis led to significantly less aGVHD (P = .03) and cGVHD (P = .04).

Association of Non-High-Density Lipoprotein Cholesterol with Psychosocial Dysfunction in Children and Adolescents with Obesity.

BACKGROUND: Children with obesity have worse psychosocial functioning compared to their non-overweight peers. Adult studies suggest that several metabolic factors may participate in the etiology of depression in obesity. METHODS: We evaluated the association of several metabolic parameters with psychosocial dysfunction in children with obesity, through a retrospective review of electronic medical records in patients ages 6-17. All parents were asked to complete the Pediatric Symptom Checklist (PSC) questionnaire, a validated measurement of psychosocial dysfunction in children. RESULTS: PSC scores were available in 618 patients. Overall, 11.2% of patients had a PSC score ≥28, suggestive of psychosocial dysfunction. Non-high-density lipoprotein (HDL) cholesterol was associated with a higher PSC score (p = 0.02), after adjusting for age, sex, race, socioeconomic status, and BMI z-score. CONCLUSIONS: Consistent with adult studies, in children and adolescents with obesity, non-HDL cholesterol may play a role in the etiology of psychosocial dysfunction. Further studies are warranted.