Reducing the toxicity of autologous haemopoetic stem cell transplants

Post-thaw washing of cryopreserved blood stem cells is intended to reduce side effects and is an increasingly common practice in Autologous Stem Cell Transplantation ( ASCT). However, the potential advantages of this extra manipulation have not been fully evaluated, and needs to be balanced against the fact that patient morbidity has already been significantly lowered by reductions in the reinfusion volume (achieved through refined harvesting, mobilising and processing techniques) and improved patient pre-medication. This study modified and validated the New York Cord Blood Banks washing protocol (Rubinstein et al. 1995). Parameters validated included; cell loss, overall viability, viable CD34+stem cell enumeration, clonogenic potential and reduction in free haemoglobin content. The results demonstrate that washing of cryopreserved stem cells improves the outcome of several key laboratory parameters without a significant negative impact upon haematopoietic stem cell (HSC) engraftment potential. To determine whether a clinical need exists for the routine washing of cryopreserved HSC autografts, a single institution, non-randomised clinical trial was performed. Patients who met trial eligibility criteria were consented for the washing of their ASCT graft, whereas all other transplant patients received thawed unwashed blood stem cells in accordance with current practice. Reinfusion associated side effects experienced by patients, their close family members (carers) and nurses following the infusion of washed or unwashed stem cells were assessed using both a Quality of Life (QOL) survey and nursing documentation forms. The surveys were self-completed by the patient, the nurse and the carer at intervals over a 24 hour period. Statistical analysis of the QOL data demonstrated that washing was associated with an improvement in several side effects associated with reinfusion including flushing, nausea and unpleasant tastes for patients and unusual smells for both carers and nurses. Furthermore, the clinical observations indicate that the washing protocol reduces transplant associated hypertension in ASCT patients and is an improvement on the reinfusion of unwashed HSC, which has a significant correlation with increased blood pressure. Consequently, this study has identified a number of circumstances in which a post-thawing washing of HSC autografts is potentially beneficial for the patients. The washing protocol reduces the amount of cellular debris and DMSO reinfused as well as diminishing patient discomfort and therefore should be considered in the event of large volume reinfusions, patient allergies or where hemodilution may exacerbate existing cardiac issues. Furthermore, post-thaw washing of HSC should also be contemplated in the event of unexpected delays between autograft thawing and reinfusion as a strategy for extending the viability of HSC