HLH

The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. T cell receptor alpha beta (TCRαβ) T lymphocyte depletion and CD19+ B lymphocyte depletion of alternative donor hematopoietic stem cell (HSC) grafts is effective in preventing GVHD, but immune reconstitution may be delayed, increasing the risk of infections. The central hypothesis of this study is that an addback of CD45RO memory T lymphocytes, derived from a fraction of the original donor peripheral stem cell product depleted of CD45RA naïve T lymphocytes, will accelerate immune reconstitution and help decrease the risk of infections in TCRab/CD19 depleted PSCT.

This is a single-arm study to investigate 1-year treatment related mortality (TRM) in patients with life threatening non-malignant and malignant hematologic disorders who do not have a matched related donor for allogeneic transplantation.

This is a pilot, open-label study to assess the safety and feasibility of using investigational drug(s) as rescue therapies for CAR T cell related CRS and HLH-like syndrome (CRHLS).

Hemophagocytic lymphohistiocytosis (HLH) associated with hematologic malignancies (HM-HLH) is a syndrome with an abysmal prognosis (10-30% 5 years overall survival). The investigators have recently established an improved diagnostic and prognostic index for HM-HLH, termed the Optimized HLH Inflammatory (OHI) index. The OHI index is comprised of the combined elevation of soluble CD25 (sCD25) \> 3,900 U/mL and ferritin \>1,000 ng/mL . However, the true incidence and outcomes of HLH/OHI+ in an unselected cohort are unknown, and so is the mechanism of HM-HLH.

The purpose of this study is to observe the impact leukaemia treatment has on gut health (microbiomes) and how quickly the gut health recovers after leukamia treatment. The gut microbiome has a number of important functions not only in the gut but within the whole body. Changes to your child's nutritional status throughout treatment may affect how well they recover from treatment. This study will monitor the impact of feeding and nutrition on nutritional status and gut health in young people undergoing treatment for leukaemia. The measurements needed to observe nutritional and gut microbiomes will occur when your child attends their routine medical appointments at Great Ormond Street Hospital. Medical treatment uses chemicals to kill leukaemia cells. The type of medications used in the treatment of leukaemia can damage the gut resulting in inflammation call mucositis. This stops the gut from working and sometimes nutrition has to be provided via a feeding tube or intravenous. Chemotherapy, mucositis and intravenous nutrition all have an impact on the gut. Little is know how the gut health recovers after treatment for leukaemia. This will be the first study to specifically monitor the impact of feeding and nutritional on gut health in children undergoing treatment for leukaemia. By understanding what changes are occurring to your child's nutritional status and gut halth during treatment and during recovery will help to develop guidelines for healthcare professionals to support optimal gut health recovery.