Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy

Blood and Marrow Transplant Program, Division of Medical and Pediatric Oncology, University of Minnesota, Box 480, 420 Delaware St SE, Minneapolis, MN 55455, USA. .
Blood (Impact Factor: 10.45). 02/2005; 105(3):1343-7. DOI: 10.1182/blood-2004-07-2717
Source: PubMed

ABSTRACT Limited umbilical cord blood (UCB) cell dose compromises the outcome of adult UCB transplantation. Therefore, to augment graft cell dose, we evaluated the safety of the combined transplantation of 2 partially human leukocyte antigen (HLA)-matched UCB units. Twenty-three patients with high-risk hematologic malignancy (median age, 24 years; range, 13-53 years) received 2 UCB units (median infused dose, 3.5 x 10(7) nucleated cell [NC]/kg; range, 1.1-6.3 x 10(7) NC/kg) after myeloablative conditioning. All evaluable patients (n = 21) engrafted at a median of 23 days (range, 15-41 days). At day 21, engraftment was derived from both donors in 24% of patients and a single donor in 76% of patients, with 1 unit predominating in all patients by day 100. Although neither nucleated or CD34(+) cell doses nor HLA-match predicted which unit would predominate, the predominating unit had a significantly higher CD3(+) dose (P < .01). Incidences of grades II-IV and III-IV acute GVHD were 65% (95% confidence interval [CI], 42%-88%) and 13% (95% CI, 0%-26%), respectively. Disease-free survival was 57% (95% CI, 35%-79%) at 1 year, with 72% (95% CI, 49%-95%) of patients alive if they received transplants while in remission. Therefore, transplantation of 2 partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents.

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    • "For this reason CB HSPCs are mainly used for the therapy of children. After the successful attempt to use two CB units for a single transplant, also adult patients were able to be cured with CB HSPCs [10] [11]. Moreover, it has been suggested that CB can be a source of stem cells other http://dx.doi. "
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    ABSTRACT: The study was aimed to determine the correlations between serum levels of cytokines (GM-CSF, IL-4, IL-10 and TNF) in maternal (MB) and cord blood (CB) and some features of cord blood hematopoietic stem and progenitor cells (CB HSPCs). Study material was MB and concomitant CB samples collected from 98 volunteers at the moment of delivery. The IL-4, IL-10, TNF and GM-CSF concentrations in serum and in supernatants from PMA-stimulated mononuclear cells isolated from both blood types were measured using BD Cytometric Bead Array Flex Set System. CB HSPCs (CD34(+)CD45(low)) proportion was also estimated by flow cytometry. The most relevant results concerned the tendency to down regulation of CB HSPCs number with an increase of IL-4, IL-10 and GM-CSF levels, only the TNF concentration seems to have no influence on HSPCs pole size. The strongest positive correlations were found between CD34(+)CD45(low) HSPCs number and IL-10 and GM-CSF in MB serum and GM-CSF and TNF from CB supernatants. The strongest negative correlations were found between CD34(+)CD45(low) HSPCs number and IL-4 and GM-CSF in CB serum and IL-10 in MB supernatants. Interestingly, we observed 'opposite correlation' between serum and supernatant from CB and MB. We concluded that elevated serum levels of IL-4, IL-10 and GM-CSF in CB are indicative of enhanced differentiation of HSPCs and characterize a normal perinatal development. Elevated levels of cytokines seem to stimulate differentiation of HSPCs what is advantageous for neonates during perinatal period. Copyright © 2015. Published by Elsevier Inc.
    Cellular Immunology 01/2015; 293(2):137-141. DOI:10.1016/j.cellimm.2015.01.005 · 1.92 Impact Factor
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    • "Over the past 25 years, umbilical cord blood (UCB) has emerged as a promising alternative source of hematopoietic stem cells (HSCs) for unrelated volunteer donor transplantation [1]. Encouraging engraftment kinetics and survival have been achieved in trials that used single rich and double-unit UCB or reduced intensity conditioning regimens [2] [3]. Furthermore, UCB offers benefits such as ease of yield, rapid availability , ability to reschedule transplantation, reduced requirements of human leucocyte antigen (HLA) match and less severe graft-versus-host disease rates [4]. "
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    ABSTRACT: Background: Umbilical cord blood (UCB) has been used as an alternative source of donor hematopoietic stem cells for hematologic transplant setting over the past decade. This study attempted to evaluate potential predictors of cord blood quality. Methods: A total of 750 UCB samples were studied (male, n = 365; female, n = 385). The impact of neonatal sex, weight and stromal cell-derived factor-1α polymorphism on the quality of these UCB samples was investigated. Results: Male neonatal UCB was significantly richer in CD34(+) cells than was female UCB (P < 0.001), whereas female UCB was richer in total nucleated cells (P = 0.01). There was a slight correlation between CD34(+) cells concentration and UCB sample weight (P < 0.01) that could be attributed to the higher weight of male neonates. The use of tetra-polymerase chain reaction to detect stromal cell-derived factor-1α polymorphisms in 180 neonates revealed no differences between A/A, G/G and A/G allelic combinations. Conclusions: These data emphasize the lack of predictive factors for CD34(+) cells and total nucleated cell concentrations in UCB samples before processing.
    Cytotherapy 10/2014; 17(1). DOI:10.1016/j.jcyt.2014.09.002 · 3.29 Impact Factor
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    • "The unit predominance may be influenced by postthaw viability24), length of time interval between the infusion of the two CB units25) and ex vivo expansion26,27). The importance of T cells to establish chimerism and to ensure stem cell engraftment has been widely documented28,29,30,31,32,33). "
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    ABSTRACT: Cord blood (CB) has been used as an important and ethical source for hematopoietic stem cell transplantation (SCT) as well as cell therapy by manufacturing mesenchymal stem cell, induced pleuripotential stem cell or just isolating mononuclear cell from CB. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. For these purposes, CB has been stored worldwide since mid-1990. In this review, I would like to briefly present the historical development of clinical uses of CB in the fields of SCT and cell therapy, particularly to review the experiences in Korea. Furthermore, I would touch the recent banking status of CB.
    Korean Journal of Pediatrics 03/2014; 57(3):110-116. DOI:10.3345/kjp.2014.57.3.110
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