1.
Cryopreservation of adult unrelated donor products in hematopoietic cell transplantation: the OneMatch experience and systematic review of the literature
Aziz, J., Morris, G., Rizk, M., Shorr, R., Mercer, D., Young, K., Allan, D.
Transfusion. 2017;57(11):2782-2789
Abstract
BACKGROUND The frequency of cryopreserving blood stem or progenitor products from unrelated donors is not known and the underlying reasons are poorly documented. Greater insight is needed to develop policies on cryopreservation that balance donor safety with patient needs. STUDY DESIGN AND METHODS Cryopreservation requests between January 1, 2014, and May 31, 2016, at the OneMatch Stem Cell and Marrow Network at Canadian Blood Services were reviewed and a systematic review of the literature was performed. RESULTS Thirty products of 719 (4.2%) unrelated donor collections facilitated by OneMatch were cryopreserved. Patient-related reasons were most common and included the need to delay transplant for continued antimicrobial treatment (six patients), patient too deconditioned to proceed with scheduled transplant (five patients), and/or need for more treatment for relapsed disease (three patients). Donor-related issues leading to cryopreservation requests were less common (five cases), mainly due to lack of donor availability after attempting to reschedule. Cryopreservation of a product that was never infused occurred infrequently (two cases, 7%). In our systematic review of the literature, 993 cases were identified in 32 published reports. Both patient-related and donor-related reasons were cited but not specifically reported, precluding quantitative insight regarding the relative frequency of causes. The impact of cryopreservation on hematopoietic engraftment appears negligible when compared to controls in a subset of studies; however, reporting of outcomes was inconsistent. CONCLUSION Future studies with standard outcome measures are needed to clarify the impact of cryopreservation on engraftment and other transplant outcomes. International guidelines that consider the ethical framework surrounding requests for donor product cryopreservation are needed. Copyright © 2017 AABB.
2.
A meta-analysis of biological variation in blood-based therapy as a precursor to bio-manufacturing
Thurman-Newell, J. A., Petzing, J. N., Williams, D. J.
Cytotherapy. 2016;18(5):686-94
Abstract
Currently cellular therapies, such as hematopoietic stem cell transplantation (HSCT), are produced at a small scale on a case-by-case basis, usually in a clinical or near-clinical setting. Meeting the demand for future cellular therapies will require a robust and scalable manufacturing process that is either designed around or controls the variation associated with biological starting materials. Understanding variation requires both a measure of the allowable variation (that does not negatively affect patient outcome) and the achievable variation (with current technology). The prevalence of HSCT makes it an ideal case study to prepare for more complex biological manufacturing with more challenging regulatory classifications. A systematic meta-analysis of the medical literature surrounding HSCT has been completed of which the key outcomes are the following: (i) the range of transplanted CD34+ cells/kg can be up to six orders of magnitude around the median for allogeneic procedures and four orders of magnitude for autologous procedures, (ii) there is no improvement in variation encountered over a period of 30 years and (iii) as study size increases, the amount of variation encountered also increases. A more detailed, stratified source from a controlled single-site clinical center is required to further define a control strategy for the manufacture of biologics. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
3.
Clinical Studies of Ex Vivo Expansion to Accelerate Engraftment After Umbilical Cord Blood Transplantation: A Systematic Review. [Review]
Kiernan, J., Damien, P., Monaghan, M., Shorr, R., McIntyre, L., Fergusson, D., Tinmouth, A., Allan, D.
Transfusion Medicine Reviews. , 2016 Dec 23. 2016
Abstract
Cell dose limits greater use of umbilical cord blood (UCB) in hematopoietic cell transplantation. The clinical benefits of ex vivo expansion need clarity to understand its potential impact. A systematic search of studies addressing UCB ex vivo expansion was conducted. Fifteen clinical studies (349 transplanted patients) and 13 registered trials were identified. The co-infusion of an expanded unit and a second unmanipulated unit (8 studies), the fractional expansion of 12% to 60% of a single unit (5 studies), and the infusion of a single expanded unit (2 studies) were reported. More recently, published studies and 12 of 13 ongoing trials involve the use of novel small molecules in addition to traditional cytokine cocktails. Higher total cell number was closely associated with faster neutrophil engraftment. Compared with historical controls, neutrophil engraftment was significantly accelerated in more recent studies using small molecules or mesenchymal stromal cells (MSC) co-culture, and in some cases, platelet recovery was also statistically improved. Recent studies using nicotinamide and StemRegenin-1 reported long-term chimerism of the expanded unit. No significant improvement in survival or other transplant-related outcomes was demonstrated for any of the strategies. Ex vivo expansion of UCB can accelerate initial neutrophil engraftment after transplant. More recent studies suggest that long-term engraftment of ex vivo expanded cord blood units is achievable. Results of larger randomized controlled trials are needed to understand the impact on patient outcomes and health care costs. Copyright © 2017 Elsevier Inc. All rights reserved.