Factors predicting haematopoietic recovery in patients undergoing autologous transplantation: 11-year experience from a single centre

Abstract

Engraftment outcomes following autologous transplantation correlate poorly to infused stem cell number. We evaluated 446 consecutive patients who underwent autologous transplantation at our centre between 2001 and 2012. The impact of pre-transplant and collection factors together with CD34(+) dosing ranges on engraftment, hospital length of stay (LOS) and survival endpoints were assessed in order to identify factors which might be optimized to improve outcomes for patients undergoing autologous transplantation using haemopoietic progenitor cells-apheresis (HPC-A). Infused CD34(+) cell dose correlated to platelet but not neutrophil recovery. Time to platelet engraftment was significantly delayed in those receiving low versus medium or high CD34(+) doses. Non-remission status was associated with slower neutrophil and platelet recovery. Increasing neutrophil contamination of HPC-A was strongly associated with slower neutrophil recovery with infused neutrophil dose/kg recipient body weight ≥3 × 10(8)/kg having a significant impact on time to neutrophil engraftment (p = 0.001). Higher neutrophil doses/kg in HPC-A were associated with days of granulocyte colony stimulation factor (G-CSF) use, HPC-A volumes >500 ml and higher NCC in HPC-A. High infused neutrophil dose/kg and age >65 years were associated with longer hospital LOS (p = 0.002 and 0.011 respectively). Only age, disease and disease status predicted disease-free survival (DFS) and overall survival (OS) in our cohort (p < 0.005). Non-relapse mortality was not affected by low dose of CD34(+) (<2 × 10(6)/kg). In conclusion, our study shows that CD34(+) remains a useful and convenient marker for assessing haemotopoietic stem cell content and overall engraftment capacity post-transplant. Neutrophil contamination of HPC-A appears to be a key factor delaying neutrophil recovery. Steps to minimize the degree of neutrophil contamination in HPC-A product may be associated with more rapid neutrophil engraftment and reduced hospital LOS.

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases

“…These findings are consistent with previous studies of autologous HCT for a variety of indications [18]. …”

Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) Regulates the Expression of B-Cell Lymphoma/Leukemia-2 (Bcl-2) and Promotes the Survival of Mesenchymal Stem Cells (MSCs) via PGC-1α/ERRα Interaction in the Absence of Serum, Hypoxia, and High Glucose Conditions

“…One of the most important problems is a large number of cell apoptosis after stem cell transplantation that restricts its curative effect [23,24]. The survival rate of stem cells is very low after transplantation, which results in greatly weakened angiogenesis, which eventually seriously restricts the clinical application of stem cell transplantation [25].…”

Cryopreservation as a Key Element in the Successful Delivery of Cell-Based Therapies—A Review

“…For cell populations such as pancreatic islets and HSC, the initial cell preparation and extraction (before cryopreservation) can have a major impact on cryopreservation outcome. An inverse correlation has been reported between HSC viability and neutrophil contamination, therefore a poor collection can lead to a poor cryopreservation outcome and poor engraftment success regardless of cryopreservation strategy used ( 121 , 132 ). A similar situation exists for pancreatic islet cryopreservation in which isolation of islets can result in losing up to half of the cellular material and it is likely that poor cryopreservation outcomes here are at least in part due to the sub-optimal condition of the surviving cells from the collection ( 136 ).…”