Terminology and labeling of cellular products: 1. Standards.

The International Cellular Therapy Coding and Labeling Advisory Group was established to address the growing need for standardization of terminology and labeling for cellular therapy products as a result of increasing international transfer of these products. This paper presents new standards for terminology and labeling. These standards have been developed through a consultative process and are supported by key professional and accreditation bodies.

Terminology and labeling of cellular products-2: Implementation plan.

The publication of new standards for terminology and labeling marks an important step in ensuring consistency and traceability of cellular therapies at the global level. However, it is only with the widespread implementation of the standard that the benefits can be truly realized. This paper provides guidance on the practical aspects of adopting these new standards for organizations with differing current levels of computerization.

Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).

Background: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients.

Objective: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients.

ISBT 128 implementation plan for cellular therapy products.

The publication of new standards for terminology and labeling marks an important step in ensuring consistency and traceability of cellular therapies at the global level. However, it is only with the widespread implementation of the standard that the benefits can be truly realized. This paper provides guidance on the practical aspects of adopting these new standards for organizations with differing current levels of computerization.

Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation.

Haploidentical hematopoietic stem-cell transplantation (HSCT) is associated with an increased risk of graft failure. Adult bone marrow-derived mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immune suppressive effects. We cotransplanted donor MSCs in 14 children undergoing transplantation of HLA-disparate CD34(+) cells from a relative.

Directed sibling cord blood banking for transplantation: the 10-year experience in the national blood service in England.

Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation. Although UCB is often collected from unrelated donors, directed umbilical cord blood (DCB) from sibling donors also provides an important source of UCB for transplantation. This report summarizes the experience in collection, testing, storage, and transplantation of DCB units by the National Blood Service for England and North Wales over 10 years.

An internal positive control for the enumeration of CD45(+) and CD34(+) cells by flow cytometry allows monitoring of reagent and operator performance.

Background: Three-color flow cytometry assays are used to determine CD34(+) cell doses prior to stem cell transplantation. These assays require high-quality reagents that are dispensed accurately to ensure reproducible results. We have developed a flow cytometry assay for CD34(+) cells with an integral positive control (KG1a cells) for monitoring reagent and operator performance.

Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion.

Ring chromosomes are rare cytogenetic findings and are associated at phenotypic level with mental retardation and congenital abnormalities. Features specific for ring chromosome syndromes often overlap with the features of terminal deletions for the corresponding chromosomes. Here, we report a case of a ring chromosome 14 which was identified by conventional cytogenetics and shown to have a terminal deletion and an additional inverted duplication with a triplication by using large insert clone and oligo array-comparative genomic hybridization (array-CGH), fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA).

Assessment of disseminated adenovirus infections using quantitative plasma PCR in adult allogeneic stem cell transplant recipients receiving reduced intensity or myeloablative conditioning.

Objectives: Disseminated adenovirus (AdV) infections following allogeneic stem cell transplantation (allo-SCT) are increasingly recognised, particularly in children. This study evaluated the clinical relevance of disseminated AdV infections in adult allo-SCT recipients, after different conditioning regimens.

Methods: In a cohort of 107 adult allo-SCT recipients, receiving either reduced intensity conditioning (RIC, n = 48) or myeloablative conditioning (MAC, n = 59), AdV DNA levels in plasma were determined retrospectively at 1, 3 and 6 months following transplantation.

Sequential emergence of multiple adenovirus serotypes after pediatric stem cell transplantation.

Background: Adenovirus infections after allogeneic stem cell transplantation (SCT), particularly in children, may be severe and protracted. Up to 51 different serotypes of adenovirus are presently recognized but serotyping is usually limited to initial viral isolates.

Objectives: A systematic and sustained analysis of adenovirus serotypes in a cohort of adenovirus-infected pediatric SCT recipients, correlated to transplant-associated variables.

Expression of cellular FLICE inhibitory protein, caspase-8, and protease inhibitor-9 in Ewing sarcoma and implications for susceptibility to cytotoxic pathways.

Purpose: Ewing sarcoma is a common pediatric bone tumor with an unfavorable prognosis for metastatic or recurrent disease. Cellular immunotherapy may provide new treatment options and depends on the cytolytic death receptor and perforin/granzyme pathways. Expression of death receptor pathway inhibitor cellular FLICE inhibitory protein (cFLIP), initiator caspase-8, and granzyme B inhibitor protease inhibitor-9 (PI-9) have been reported to determine susceptibility to cell- and chemotherapy-mediated killing in several tumor types.

Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes.

We studied the pharmacokinetics and clinical outcome of a new once-daily intravenous area under the curve-targeted dosing scheme for busulfan based on body surface area. Eighteen children undergoing busulfan-based conditioning for allogeneic stem cell transplantation were enrolled. The age of the children ranged from 0.

Management of Epstein-Barr virus (EBV) reactivation after allogeneic stem cell transplantation by simultaneous analysis of EBV DNA load and EBV-specific T cell reconstitution.

Background: Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation and may progress to life-threatening lymphoproliferative disease (EBV-LPD) in the absence of adequate EBV-specific T cell immunity. Quantification of EBV DNA load in asymptomatic individuals who are at risk is a useful (although not entirely predictive) indicator of progression to EBV-LPD and guide for preemptive treatment with CD20 antibodies.

Methods: With the aim of improving the identification of patients at risk, we retrospectively analyzed, within a cohort of 25 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD, the pattern of T cell reconstitution during EBV reactivation in all preemptively treated patients (8 patients).

A possible role for CCL27/CTACK-CCR10 interaction in recruiting CD4 T cells to skin in human graft-versus-host disease.

Graft-versus-host disease (GvHD) is a serious complication of allogeneic stem cell transplantation (SCT) affecting the skin, gut and liver. The involvement of distinct organs suggests a role for tissue-specific chemokines and their receptors in directing activated donor T cells to these sites. In this study the potential involvement of the skin-specific CCL27/CTACK-CCR10 interaction was investigated in 15 paediatric SCT patients with skin GvHD.

Limited rescue of osteoclast-poor osteopetrosis after successful engraftment by cord blood from an unrelated donor.

Unlabelled: We report on a case of osteoclast-poor osteopetrosis who received a hematopoietic stem cell graft and, despite hematological engraftment, showed little signs of response in the skeletal defect. Clinical and laboratory studies supported the concept that the bone microenvironment remained abnormal, thus reducing the clinical response to transplantation.

Introduction: Osteopetrosis is a rare genetic disorder characterized by severely reduced bone resorption resulting from a defect in either osteoclast development (osteoclast-poor osteopetrosis) or activation (osteoclast-rich osteopetrosis).

Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression.

The role of specific transcription factors in the initiation and regulation of Ig gene rearrangements has been studied extensively in mouse models, but data on normal human precursor B cell differentiation are limited. We purified five human precursor B cell subsets, and assessed and quantified their IGH, IGK, and IGL gene rearrangement patterns and gene expression profiles. Pro-B cells already massively initiate D(H)-J(H) rearrangements, which are completed with V(H)-DJ(H) rearrangements in pre-B-I cells.

Allogeneic stem cell transplantation in X-linked lymphoproliferative disease: two cases in one family and review of the literature.

X-linked lymphoproliferative disease (XLP) is a rare immunodeficiency caused by mutations in the signaling lymphocyte activating molecule-associated protein/SH2D1A gene and characterized by a dysregulated immune response to Epstein-Barr virus and other pathogens. The clinical presentation is heterogeneous and includes fulminant infectious mononucleosis, lymphoma, hypogammaglobulinemia and aplastic anemia. XLP is associated with a high morbidity and overall outcome is poor.

Internally controlled real-time PCR monitoring of adenovirus DNA load in serum or plasma of transplant recipients.

Adenoviruses have been recognized as important pathogens in immunocompromised hosts. Particularly in pediatric allogeneic stem cell transplant recipients, the morbidity of the patients and mortality in those patients with disseminated infections have been found to increase over the last few years. Severe infections are predominantly but not exclusively caused by subgroup C adenoviruses.

Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity.

Human adenoviruses (HAdV) are a frequent cause of potentially fatal infections in patients after allogeneic stem cell transplantation, especially in children. Monitoring of serum/plasma by real-time quantitative PCR is a sensitive tool for the recognition of patients at risk of a potentially fatal infection and for the evaluation of the efficacy of treatment. Data from a retrospective study and from a prospective study demonstrate that recovery of immunity after transplantation is essential for the elimination of HAdV infection.

Graft dysfunction and delayed immune reconstitution following haploidentical peripheral blood hematopoietic stem cell transplantation.

For many children with life-threatening hematological diseases, hematopoietic stem cell transplantation (HSCT) is the only curative option. In children lacking a matched related or unrelated donor and with the certainty that, left untreated, death will ensue alternative donors must be sought. Haplo-identical peripheral blood stem cell transplantation (PBSCT) from a healthy parent is a feasible alternative.

High peripheral blood progenitor cell counts enable autologous backup before stem cell transplantation for malignant infantile osteopetrosis.

Autosomal recessive osteopetrosis (OP) is a rare, lethal disorder in which osteoclasts are absent or nonfunctional, resulting in a bone marrow cavity insufficient to support hematopoiesis. Because osteoclasts are derived from hematopoietic precursors, allogeneic hematopoietic cell transplantation can cure the bony manifestations of the disorder. However, high rates of graft failure have been observed in this population.