Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: HISTORICAL PERSPECTIVE
Stem cell therapy was commenced after using rabbits as research models. Once this process was successful,
the first human transplant was done in 1974.
Certain prerequisites were necessary and these were achieved - a protected environment, an apheresis unit,
protocols and accreditation with International Registries.
Initially, unmanipulated bone marrow and peripheral blood stem cells were used together with
immunosuppressive drugs followed by the use of Cyclosporin A then the addition of ex vivo Campath®.
AUDIT OF ACUTE ASSOCIATIONS (468 subjects in initial cohort)
NEPHROLOGY
Creatinine was used as an indication of renal function. Of the 76 available for analysis, 47% had acute kidney
injury. Dialysis had a poor outcome as reported in the literature. Renal complications occurred frequently
mostly due to infection.
CARDIOLOGY
A total of 119 individuals were available for analysis. Echocardiograms and electrocardiograms were part of
pre-transplant assessment. Left ventricular systolic dysfunction predicted for increasing post transplant
problems. Cardiac complications occurred at a lower frequency than other post-transplants side-effects
consistent with the published data.
DERMATOLOGY
Cases were evaluated on a daily basis and referred to a dermatologist when necessary.
To confirm Graft-Versus-Host Disease (GVHD), a skin biopsy was done to differentiate it from drug
hypersensitivity or viral infections.
The exposure to ex vivo Campath® significantly improved outcome by reducing the incidence and severity of
GVHD. Quality of life was enhanced with substantial cost saving.
GASTROENTEROLOGY
Foregut symptoms occurred in 90% of patients. Nutritional problems were encountered. Altered liver
functions were relatively common attributable to drugs, sepsis and conditioning regimens. Liver biopsies were
not performed in this series and endoscopy performed only when necessary.
A STUDY ON LATE COMPLICATIONS (55 subjects)
RESPIRATORY
Spirometry and diffusing capacity were done in this cohort. All the lung function studies were within the
predicted normal range apart from some marginal reduction in diffusing capacity. In none of these patients
did late consequences such as Bronchiolitis Obliterans Organising Pneumonia and Late Onset Non-Infectious
Pulmonary complications occur. Cytomegalovirus reactivation was common but early intervention prevented
serious complications.
IMMUNOLOGY
An in vitro functional study was done.
Both the innate and adaptive systems were evaluated. Taken into consideration were the type of transplant,
age from transplant, diagnosis and conditioning.
The granulocyte Burst-test was done for the innate profile. Reduced activity was shown in all the subgroups. It
appears as if the innate response of the granulocytic cells never recovered due to reduced granulocytic function
in vitro.
The adaptive responses were evaluated in vitro and only the autografts showed better CD4+ and CD8+
cytokine production. No major differences were seen in other groups.
Normal cytokine production by CD4+ and CD8+ T cells were present when these were activated in vitro to
produce regulatory cytokines, implying that their lymphoid component was intact post-transplant.
BONE DISEASE
Here both the Dual energy X-ray Absorptiometry (DXA) and Quantitative Computed Tomography (QCT) were
used to evaluate bone mineral density. There was a discrepancy present between the two modalities. DXA
showed no osteoporosis but QCT 22%. Biomarkers were normal in all. There was no history of fracture and no
objective evidence of vertebral fractures using vertebral fracture assessment.
Although QCT was used for the study, DXA remains the gold standard in South Africa.
CONCLUSION
This doctoral provided information on the non-haematological consequences in South Africa with the use of
Campath® ex vivo. / AFRIKAANSE OPSOMMING: HISTORIESE PERSPEKTIEF
Stamsel terapie is voortgesit nadat konyne aanvanklik as navorsingsmodelle gebruik is. Na suksesvolle
voltooiing van hierdie proses, is die eerste menslike oorplanting gedoen in 1974.
Sekere voorvereistes was nodig en hierdie was bereik – ʼn beskermde omgewing, ʼn aferese eenheid, protokolle
en akkreditasie by Internasionale Registers.
Aanvanklik is ongemanipuleerde beenmurg- en perifere bloed stamselle gebruik, tesame met
immuunonderdrukkende middels, gevolg deur die gebruik van Sikloporien A en daarna die toevoeging van ex
vivo Campath®.
OUDIT VAN AKUTE ASSOSIASIES (468 GEVALLE IN DIE OORSPRONKLIKE GROEP)
NEFROLOGIE
Kreatinien is gebruik as ʼn aanduiding van nierfunksie. Van die 76 gevalle beskikbaar vir ontleding, het 47%
akute nierbeserings gehad. Dialise het ʼn swak uitkoms gehad soos gerapporteer in publikasies. Nier
komplikasies het gereeld voorgekom, meestal as gevolg van infeksie.
KARDIOLOGIE
ʼn Totaal van 119 gevalle was beskikbaar vir ontleding. Eggokardiogramme en elektrokardiogramme was deel
van die pre-oorplanting assessering. Linker ventrikulêre disfunksie was voorspelbaar van verhoogde postoorplanting
probleme. Kardiale komplikasies het konstant volgens publikasies minder geredelik voorgekom
as ander post-oorplantings newe-effekte.
DERMATOLOGIE
Gevalle is op ʼn daaglikse basis geëvalueer en verwys na ʼn dermatoloog wanneer nodig.
ʼn Velbiopsie is gedoen om “Graft-Versus-Host” siekte (GVHD) te bevestig en dit te onderskei van middel
hipersensitiwiteit of virale infeksies.
Die blootstelling aan ex vivo Campath® het uitkomste aansienlik verbeter deur die voorkoms en erns van
GVHD te verminder. Kwaliteit van lewe is verhoog met aansienlike koste besparing.
GASTROENTEROLOGIE
Boonste gastro-intestinale simptome het voorgekom in 90% van die pasiënte. Wanvoeding het voorgekom..
Abnormale lewerfunksies was relatief algemeen toeskryfbaar aan middels, sepsis en kondisionerings
protokolle. Lewer biopsies is nie in hierdie reeks uitgevoer nie en endoskopie slegs wanneer dit noodsaaklik
was.
DIE STUDIE VAN LAAT KOMPLIKASIES (55 GEVALLE)
RESPIRATORIES
Spirometrie en diffusie kapasiteit is gedoen in hierdie groep. Al die longfunksie ondersoeke was binne die
voorspelde normale waardes behalwe ʼn paar marginale afnames in die diffusie kapasitiet. In geen van hierdie
pasiënte het laat nagevolge soos Bronchoilitis Obliterans Organiserende Pneumonie en Laat Aanvangs Nieinfektiewe
Long komplikasies voorgekom nie. Sitomegaal virus heraktivering was algemeen maar vroeë
intervensie het ernstige komplikasies voorkom.
IMMUNOLOGIE
ʼn In vitro funksionele studie is gedoen.
Beide die spesifieke en nie-spesifieke immuun stelsels is geëvalueer. Die tipe oorplanting, tyd vanaf
oorplanting, diagnose en kondisionering is in ag geneem.
Die “Granulocyte Burst” toets is gedoen vir die nie-spesifieke profiel. Verminderde aktiwiteite is bewys in al
die subgroepe. Dit wil voorkom asof die nie-spesifieke respons van die granulosiete nooit herstel nie as gevolg
van die verlaagde in vitro granulosiet funksie.
Die spesifieke immuun respons is in vitro geëvalueer en slegs die outotransplantaat het beter CD4+ en CD8+
sitokiene produksie getoon. Geen groot verskille is gesien in ander groepe nie.
By CD4+ en CD8+ T selle was normale sitokiene produksie teenwoordig toe dit in vitro geaktiveer is om
regulatoriese sitokiene produksie te produseer, wat beteken dat hul limfoïede komponent na oorplanting
ongeskonde was.
BEEN SIEKTE
Beide die Dubbele energie x-straal absorpsiemetrie (DXA) en Kwantitatiewe rekenaar tomografie (QCT) is hier
gebruik om been mineraal digtheid te evalueer. Daar was ʼn teenstrydigheid teenwoordig tussen die twee
modaliteite. DXA het geen osteoporose getoon nie maar QCT het 22% getoon. Biomerkers was normaal in
albei. Daar was geen geskiedenis van frakture en geen objektiewe bewyse van vertebrale frakture met
Vertebrale Fraktuur Assessering nie.
Alhoewel QCT gebruik is vir die studie bly DXA die goue standaard in Suid-Afrika.
GEVOLGTREKKING
Hierdie doktoraal verskaf inligting oor die nie-hematologiese gevolge in Suid-Afrika met die gebruik van
Campath® ex vivo.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/96785 |
| Date | 03 1900 |
| Creators | Wood, Lucille |
| Contributors | Jacobs, Peter, Irusen, Elvis, Abayomi, Akin, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. General Internal Medicine. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 260 pages : illustrations |
| Rights | Stellenbosch University |
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