None listed
Conditions
Brief summary
The application of allogeneic haematopoietic stem cell transplantation (HSCT) is hampered by procedure-related morbidity and mortality, including transplant-associated thrombotic microangiopathy (TA-TMA), sinusoidal obstructive syndrome of the liver (SOS), idiopathic pneumonia syndrome (IPS) and acute graft vs host disease (aGVHD). While the aetiology of many of these conditions is not known, it has been postulated that endothelial toxicity related to the chemotherapy conditioning is an early event common to all of them. We hypothesise that endothelial toxicity is associated with complement dysregulation, and leads to a prothrombotic state with impaired fibrinolysis, which manifest as the clinical complications listed above. In this study, we aim to document laboratory evidence of changes in coagulation and fibrinolytic potential occurring after allogeneic HSCT, and to correlate this with prospectively identified clinical and laboratory manifestations of endothelial toxicity. A total of 30 participants will be recruited, of which a minimum of 15 will have received the busulfan / cyclophosphamide regimen. Blood samples will be taken from recipients immediately prior to commencement of the conditioning regimen, on the day of transplantation, and on post-transplant days 7, 14 and 21. Additional blood samples will be taken for therapeutic dose monitoring from recipients of busulfan conditioning. Diagnoses of TA-TMA, SOS, IPS and aGVHD occurring up to post-transplant day 28 will be made according to specified criteria using diagnostic information collected as part of standard care.
Interventions
Blood samples will be taken from recipients immediately prior to commencement of the conditioning regimen, on the day of transplantation, and on post-transplant days 7, 14 and 21. In addition, for the subset of patients receiving busulphan, a total of 8 additional samples will be taken on days 1 (6 samples), 3 (1 sample) and 4(1 sample) of busulphan dosing.
Myeloablative allogeneic stem cell transplantation will be performed according to standard institutional care and will include the followin
Blood samples will be taken from recipients immediately prior to commencement of the conditioning regimen, on the day of transplantation, and on post-transplant days 7, 14 and 21. In addition, for the subset of patients receiving busulphan, a total of 8 additional samples will be taken on days 1 (6 samples), 3 (1 sample) and 4(1 sample) of busulphan dosing. Myeloablative allogeneic stem cell transplantation will be performed according to standard institutional care and will include the following: 1. Conditioning regimen. Either cyclophosphamide (60mg/kg IV for 2 days) and busuphan (1mg/kg PO for 4 days); cyclophosphamide (60mg/kg IV for 2 days) and total body irradiation (total 12 Gray over 3 days); or fludarabine (30mg/m^2 IV for 5 days) and melphalan (140mg/m^2 for 1 day). 2. Infusion of allogeneic stem cells (matched sibling donor, matched unrelated donor, mismatched unrelated adult or cord blood donor) 3. Graft versus host disease prophylaxis (methotrexate 15mg/m^2 IV on day +1, 10mg/m^2 IV on days +3, +6 and +11) and cyclopsporine (commence day -1 at 1.5mg/kg IV twice daily). 4. Antimicrobial prophylaxis per institutional guideline
Sponsors
Fiona Stanley Hospital
Eligibility
Sex/Gender
All
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Completed work-up and planned to proceed with allogeneic HSCT at Fiona Stanley Hospital 2. Has had sufficient work-up to enable haematopoietic cell transplantation-specific comorbidity index (HCT-CI) to be calculated (minimum: history and examination, lung function studies, assessment of cardiac ejection fraction) 3. Will receive one of the following conditioning regimens: busulfan + cyclophosphamide, TBI + cyclophosphamide or fludarabine + melphalan 4. Will receive GVHD prophylaxis with a calcineurin inhibitor (cyclosporine or tacrolimus) and short course methotrexate, with or without ATG 5. Provides informed consent to participate in the study
Exclusion criteria
1. Incomplete pre-transplant work-up (see inclusion criteria 2 above) 2. Will receive a conditioning regimen or GVHD prophylaxis regimen other than those specified in the inclusion criteria
Outcome results
None listed