Severe pruritus and hypothermia as the primary manifestations of human herpes virus-6 encephalitis after pediatric cord blood transplantation.
Bone Marrow Transplant. 2012 Jan;47(1):153-4
Authors: Hudspeth M, Brown E, Ragucci D, Dixon T, Turner R
PMID: 21358680 [PubMed - indexed for MEDLINE]
Unrelated cord blood transplantation for thalassaemia: a single-institution experience of 35 patients.
Bone Marrow Transplant. 2012 Jan;47(1):33-9
Authors: Jaing TH, Hung IJ, Yang CP, Chen SH, Chung HT, Tsay PK, Wen YC
Abstract
Our study was designed to prospectively determine whether or not unrelated cord blood transplantation (CBT) can produce outcomes comparable to related donor transplantation for children with β-thalassaemia. In 35 patients, 40 transplants were performed between October 2003 and September 2009. HLA matching at enrolment was 6/6 (n=8), 5/6 (n=16), 4/6 (n=27), or 3/6 (n=1) by low-resolution HLA-A, -B, and high-resolution DRB1. These patients received non-manipulated grafts without ex vivo expansion or T-cell depletion. The median number of nucleated and CD34+ cells infused was 7.8 × 10(7)/kg (range, 2.8-14.7 × 10(7)/kg) and 4.0 × 10(5)/kg (range, 1.7-19.9 × 10(5)/kg), respectively. The 5-year OS and thalassaemia-free survival after the first transplant were 88.3 and 73.9%, respectively. The cumulative incidence of TRM at 2 years was 11.7%. Fourteen patients developed chronic skin GVHD. Thirty patients were alive and transfusion-independent with a Lansky performance score ≥80% achieved between 6 and 76 months post transplant (median, 36 months). These data compare acceptably with the survival rates of related-donor BMT for thalassaemia and suggest that patients without an available HLA-compatible sibling but who have well-matched unrelated donors should also be considered for CBT.
PMID: 21383683 [PubMed - indexed for MEDLINE]
European regulations on cord blood banking: an overview.
Transfusion. 2012 Mar;52(3):668-79
Authors: Petrini C
PMID: 21790628 [PubMed - indexed for MEDLINE]
Flow cytometry assessment of apoptotic CD34+ cells by annexin V labeling may improve prediction of cord blood potency for engraftment.
Transfusion. 2012 Mar;52(3):549-59
Authors: Duggleby RC, Querol S, Davy RC, Fry LJ, Gibson DA, Horton RB, Mahmood SN, Gomez SG, Madrigal JA
Abstract
BACKGROUND: Nonviable CD34+ cells are commonly assessed by standard flow cytometry using the nuclear stain 7-aminoactinomycin D (7AAD). 7AAD, however, only detects necrotic and late apoptotic cells, not earlier apoptosis, which engraft poorly in animal models of cord blood (cord) transplantation. The standard method, therefore, may overestimate engraftment potency of cord units under certain conditions.
STUDY DESIGN AND METHODS: To detect apoptotic events, costaining with 7AAD and annexin V (AnnV), in parallel with the quantitative, standard enumeration, was used. Cord units were assessed before and after cryopreservation using both staining methods and colony-forming units (CFU) to determine if graft potency can be predicted using a "functional flow cytometry" approach.
RESULTS: Significant numbers of CD34+ AnnV+ events were found within the 7AAD-gated population. Nonapoptotic cell dose (CD34+ AnnV-) correlated well with CFUs in both a small-scale (n = 10) and a large-scale banking study (n = 107). Finally, following samples postthaw with time showed increasing numbers of apoptotic CD34+ cells and consequently the AnnV assessed dose was better at predicting the CFU compared with just the standard enumeration.
CONCLUSION: Defining the apoptotic population of CD34+ cells improved the prediction of CFU, making this method a rapid test of potency for assessment of cord units for clinical use.
PMID: 21883264 [PubMed - indexed for MEDLINE]
Information from your family doctor. Umbilical cord blood.
Am Fam Physician. 2011 Sep 15;84(6):667-8
Authors:
PMID: 21916392 [PubMed - indexed for MEDLINE]
Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant.
Br J Haematol. 2012 Mar;156(5):656-66
Authors: Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJ, Zhan H, Montiel-Equihua CA, Derniame S, Cale C, Rao K, Hiwarkar P, Hough R, Saudemont A, Fahrenkrog CS, Goulden N, Amrolia PJ, Veys P
Abstract
Umbilical cord blood transplant (UCBT) is associated with impaired early immune reconstitution. This might be explained by a lower T-cell dose infused, the naivety of cord blood T-cells and the use of in vivo T-cell depletion. We studied the pattern of early immune reconstitution and the clinical outcome of children undergoing unrelated UCBT when in vivo T-cell depletion was omitted. Thirty children affected by malignancies (46%) or immunodeficiencies (54%) underwent an unrelated UCBT. Prospective assessment of immune reconstitution and clinical outcome was performed. We observed an unprecedented CD4(+) T-cell reconstitution, with a median cell count at 30 and 60 d post UCBT of 0.3 × 10(9) /l and 0.56 × 10(9) /l, respectively. Early T-cell expansion was thymic-independent, with a rapid shift from naïve to central memory phenotype and early regulatory T-cell recovery. Viral infections were frequent (63%) but resolved rapidly in most cases and virus-specific T-lymphocytes were detected within 2 months post-UCBT. Acute graft-versus-host disease (GvHD) was frequent (grade II = 34%, grade III-IV = 16%) but steroid responsive, and the incidence of chronic GvHD was low (14%). The omission of in vivo T-cell depletion promotes a unique thymic-independent CD4(+) T-cell reconstitution after unrelated UCBT in children. We postulate that this relates to the specific immunological and ontological qualities of fetal-derived lymphocytes.
PMID: 22224700 [PubMed - indexed for MEDLINE]
Microchimerism in cord blood: mother as anticancer drug.
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2190-1
Authors: Burlingham WJ, Nelson JL
PMID: 22323582 [PubMed - indexed for MEDLINE]
Umbilical cord blood-derived very mall embryonic like stem cells (VSELs) as a source of pluripotent stem cells for regenerative medicine.
Pediatr Endocrinol Rev. 2012 Mar;9(3):639-43
Authors: Ratajczak MZ, Suszynska M, Pedziwiatr D, Mierzejewska K, Greco NJ
Abstract
Umbilical cord blood-derived very small embryonic-like stem cells (UCB-VSELs) are the most primitive stem cells circulating in fetal peripheral blood. These very rare cells slightly smaller than red blood cells i) become mobilized during delivery, ii) are enriched in fraction of CD133+ Lin-CD45- cells iii) express markers of pluripotent stem cells (e.g., Oct4, Nanog, and SSEA-4) and iv) display a distinct morphology characterized by a high nuclear/ cytoplasmic ratio and undifferentiated chromatin. We envision that VSELs are released into neonatal peripheral blood as a migrating population of stem cells involved in regeneration of tissues that become damaged in the process of delivery. They may also be responsible for the occurrence of fetal-maternal chimerism. Our most recent data suggest that UCB-VSELs exhibit some characteristics of long-term repopulating hematopoietic stem cells (LT-HSCs). We propose that UCB-VSELs may eventually be employed as a source of pluripotent stem cells in regenerative medicine.
PMID: 22523831 [PubMed - in process]
Comparison of pre-cryopreserved and post-thaw-and-wash-nucleated cell count on major outcomes following unrelated cord blood transplant in children.
Pediatr Transplant. 2012 Apr 26;
Authors: McManus MP, Wang L, Calder C, Manes B, Evans M, Bruce K, Ho RH, Domm J, Frangoul H
Abstract
McManus MP, Wang L, Calder C, Manes B, Evans M, Bruce K, Ho RH, Domm J, Frangoul H. Comparison of pre-cryopreserved and post-thaw-and-wash-nucleated cell count on major outcomes following unrelated cord blood transplant in children. Abstract: Engraftment and OS after umbilical CBT is highly dependent on the TNC. The contribution of the wash step to cell loss and ultimately the dose of cells available for transplant is not well described. To investigate the amount of cell loss after washing and its impact on major outcomes compared to pre-cryopreserved TNC, we analyzed data from patients prospectively enrolled on a National Heart, Lung and Blood Institute sponsored cord blood transplant study between 1999 and 2003. There were 310 patients ≤18 yr of age with malignant (N = 218) or non-malignant (N = 92) disease enrolled on this trial. Only single CBU were used. All CBU were thawed and washed using an identical process. The median TNC after thawing and washing (PTW) was 5.43 × 10(7) /kg (79% recovery of cells). The cumulative incidence of neutrophil engraftment was significantly higher in patients receiving a PTW TNC ≥2.5 × 10(7) /kg (p = 0.01). The cumulative incidence of TRM was higher among patients receiving post-thaw-and-wash TNC <2.5 × 10(7) /kg (p = 0.039). In conclusion, receiving a PTW TNC of <2.5 × 10(7) /kg resulted in worse neutrophil engraftment and increased transplant-related mortality compared to a PTW TNC of ≥2.5 × 10(7) /kg.
PMID: 22533817 [PubMed - as supplied by publisher]
Pluripotent VSELs Get Discarded during Cord Blood & Bone Marrow Processing.
Stem Cells Dev. 2012 Apr 27;
Authors: Bhartiya D
Abstract
The recent letter by Ivanovic commenting on work published by our group on very small embryonic-like stem cells (VSELs) in cord blood and bone marrow raises important questions on the properties and regenerative potential of VSELs. Similar to embryonic stem cells, being pluripotent by nature, VSELs are expected to have maximum regenerative potential compared to adult stem cells with limited 'plasticity'. We propose that both HSCs and MSCs (with cytoplasmic OCT-4) are possibly descendants 'progenitors' derived from VSELs (with nuclear OCT-4). Being pluripotent and quiescent by nature, VSELs may serve as a good autologus source of pluripotent stem cells (with minimal risk of teratoma formation) for regenerative medicine.
PMID: 22540984 [PubMed - as supplied by publisher]
