Care of Children with DiGeorge Before and After Cultured Thymus Tissue Implantation

Abstract Background Children with complete DiGeorge anomaly (cDGA) have congenital athymia plus a myriad of other challenging clinical conditions. The term cDGA encompasses children with congenital athymia secondary to 22q11.2DS, CHARGE syndrome (coloboma, heart defects, choanal atresia, growth or mental retardation, genital abnormalities, and ear abnormalities and/or deafness), and other genetic abnormalities. Some children have no known genetic defects. Since 1993, more than 100 children with congenital athymia have been treated with cultured thymus tissue implantation (CTTI). Naïve T cells develop approximately 6 to 12 months after CTTI. Most of the children had significant comorbidities such as heart disease, hypoparathyroidism, and infections requiring complex clinical care post cultured thymus tissue implantation (CTTI). Objective The purpose of this guidance is to assist multidisciplinary teams in caring for children with cDGA both before and after CTTI. Methods Thirty-one specialists, in addition to the authors, were asked to share their experience in caring for children with cDGA at Duke University Health System, before and after CTTI. These specialists included physicians, nurses, dentists, therapists, and dieticians. Results The goal of a multidisciplinary approach is to have children in the best possible condition for receiving CTTI and provide optimal care post CTTI through development of naïve T cells and beyond. The CTT (cultured thymus tissue) must be protected from high doses of steroids which can damage CTT. Organs must be protected from adverse effects of immunosuppression. Conclusion Creating a multidisciplinary team and a detailed plan of care for children with cDGA is important for optimal outcomes.

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Depletion of CD45RA+ Cells from Mobilized Peripheral Blood Stem Cell (PBSC) Collections As an Integral Part of Hematopoietic Stem Cell Transplantation (HSCT) and Cellular Therapy (CT)

Blood ◽

10.1182/blood.v124.21.1130.1130 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1130-1130

Author(s):

Ping Law ◽

Paul W. Eldridge ◽

James Houston ◽

Brandon M. Triplett ◽

David R Shook ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

Conflicts Of Interest ◽

Cell Depletion ◽

Clinical Scale ◽

Hematopoietic Stem ◽

Naive T Cells ◽

Naïve T Cells ◽

Cd34 Cells ◽

Before And After

Abstract Clinical scale depletion of CD45RA+ naïve T cells from leukapheresis collections can be achieved using CliniMACS (Bone Marrow Transplant. 2013, 1-7). In this study, PBSC collections depleted of CD45RA+ cells were infused as part of CT treatment protocols for pediatric patients with hematologic malignancies and solid tumors in 2 separate clinical trials. Between Sep 2012 and May 2014, a total of 25 CD45RA+ cell depletion procedures was performed for 25 patients. Mobilized PBSC leukapheresis units were collected (using Spectra) from HLA haplo-identical donors and held overnight in cold prior to cell selection. Characterization of the products before and after CD45RA+ cell depletion is shown in Table 1. Depletion of all CD45RA+ cell averaged to 3.39-log while depletion of CD3+CD45RA+ T cells was > 3.76-log, as this subset of cells became undetectable in 8 (out of 25) final products. CD34+ cell recovery was 65.4%, similar to that of CD3+CD45RO+ T cells (65.1%), which constituted > 99% of all T cells after depletion. From the PBSC collection, each patient received a median dose of 0.009 x 106 CD3+CD45RA+ cells/kg and 11.1 x 106 CD34+ cells/kg. The final product contained a substantial amount of CD14+ monocytes (median = 22.0%, range: 7.0 – 46.4), few CD56+ NK cells (3.1%, range: 1.3 – 8.1) and almost no CD19+ B cells (0.04%, range: 0.01 – 0.30). After processing the cells were resuspended in Plasmalyte + 5% human serum albumin and infused as soon as possible. There was no reported contamination (growth of bacteria – aerobic or anaerobic and fungus) in the final cell products and no infusion related adverse events were observed. In conclusion, we have demonstrated clinical scale depletion of naïve T cells can be achieved consistently and the final cell product can be safely infused into patients as part of HSCT and / or CT program. Table 1: Cell Populations (Median & ranges) Before and After CD45+ Cell Depletion Before Depletion After Depletion Total Nucleated Cells 3.97 x 1010 (1.55 – 6.60) 1.47 x 1010 (0.43 – 2.92) % CD34+ Cells 0.85% (0.29 – 2.30) 1.45% (0.32 – 4.63) % CD3+ T Cells 22.8% (11.5 – 50.9) 13.1% (3.9 – 37.7) % CD45RA+ Cells 39.6% (27.2 – 64.1) 0.05% (0.01 – 0.79) % CD3+ CD45RA+ Naïve T Cells 12.3% (4.3 – 29.2) 0.01% (0 – 3.42) % CD3+ CD45RO+ Memory T Cells 6.5% (2.0 – 15.6) 13.0% (3.9 – 37.5) Disclosures No relevant conflicts of interest to declare.

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