33 research outputs found
Archival Film: New Opportunities for Case Study Development and Presentation?
The potential opportunities and limitations of utilising archival film as a primary data source have received very little attention from business historians. Archival film can be a rich source of oral and visual material for the development and presentation of historical case study material, but it can also be utilised as a powerful research tool. The paper draws on the experiences of the author, who produced two films during a study of the history of the South Coast Labour Council (SCLC). The SCLC is the peak union body for the Illawarra region of NSW. During the study access to one of the region’s local television newsreel archives provided a rare opportunity to work with primary data that significantly extended the range of possibilities for rich case study development and presentation. The resulting artefacts included 1) a 15 minutes documentary on the 75 year history of the SCLC and; 2) a two hour set of selected historical excerpts. The presentation explores first, a range of essential processes that require consideration when working with this form of data. Issues explored include: 1) access, 2) equipment and 3) production processes. Second, the paper explores a range of research methods that allowed a deeper exploration of the history of the organisation post production. This section includes methods for eliciting memories in focus groups and small groups.The symposium is organised on behalf of AAHANZBS by the Business and Labour History Group, The University of Sydney, with the financial support of the University’s Faculty of Economics and Business
Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation
The International Prognostic Scoring System has been revised (IPSS-R) to predict prognosis of patients with myelodysplastic syndromes at diagnosis. To validate the use of the IPSS-R assesse
Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation
Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple costimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells. Likewise, we documented the frequent loss of surface expression of HLA-DR, -DQ and -DP on leukemia cells, due to downregulation of the HLA class II regulator CIITA. We show that loss of HLA class II expression and upregulation of inhibitory checkpoint molecules represent alternative modalities to abolish AML recognition from donor-derived T cells, and can be counteracted by interferon-gamma or checkpoint blockade, respectively. Our results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies
Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients
Following myelo-ablative treatment and
allogeneic bone marrow transplantation (BMT) in
chronic myelogenous leukemia (CML) histopathological
features assumed to exert a sienificant i m ~ a c ot n
engraftment have been rarely inve;igated systekatically.
This review is focused on immunohistochemical and
morphometric techniques involving nucleated erythroid
precursors, resident macrophages and their various
subsets, megakaryocytes and finally argyrophilic
(reticulin-collagen) fibers. Regarding standardized
intervals of examination in the postgraft sequential
trephine biopsies a pronounced reduction in cellularity
was obvious and accompanied by a decrease in the
quantity of erythro- and megakaryopoiesis. A significant
correlation between the number of erythroid precursors
and CD68+-macrophages could be determined in the
areas of regenerating hematopoiesis. This finding is in
keeping with the important functional role of the
centrally localized mature macrophages during
erythropoiesis. A relevant pretransplant reduction of the
red cell lineage and an early to advanced reticulin
fibrosis were correlated with a low hemoglobin leve1
(anemia) and splenomegaly and furthermore associated
with a significant delay to reach transfusion
independence. This result was supported by
corresponding findings in biopsy specimens performed
shortly after day 30 following BMT (standard interval
for assessment of engraftment). Samples revealed an
enhancement of fiber density and a conspicuous decrease
in the amount of erythropoiesis in the small fraction of
patients who did not conform with the usually accepted
criteria for successful hematopoietic reconstitution.
Considering the compartment of histiocytic reticular
cells the recurrence of Pseudo-Gaucher cells (PCGs) in
the engrafted donor marrow was remarkable and most
prominently expressed in the first two months following
BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in
the seque1 of myelo-ablative therapy (scavenger
macrophages). According to planimetric measurements
in the postgraft bone marrow the atypical dwarf-like
CD61+-megakaryocytes characteristic for CML
disappeared. On the other hand, normalization of
megakaryocyte size and nuclear lobulation were absent
in sequential examination of the few patients developing
a leukemic relapse. In a number of patients with
manifest myelofibrosis at onset, an initial regression
after BMT was followed by an insidiously occurring
retrieval which was concentrated on the areas of
reconstituting hematopoiesis. Similar to its relevant
pretransplant association the postgraft reappearance of
myelofibrosis was significantly correlated with the
quantity of CD61+-megakaryocytes. Altogether a
number of histological features in the pre-and postgraft
bone marrow exhibited significant correlations with each
other and thus indicated functional relationships.
Moreover, quantity of erythropoiesis and amount of
reticulin fibers (myelofibrosis) exerted a significant
impact on engraftment status
Dynamics of lineage-restricted mixed chimerism following sex-mismatched allogeneic bone marrow transplantation
Scant knowledge is available about the
dynamics of lineage-specific mixed chimerism (Ch)
following bone marrow transplantation (BMT). This
review is focused on findings derived from bone marrow
(BM) biopsies in patients with chronic myeloid leukemia
(CML) including a sex-mismatched host/donor
constellation. Appropriate techniques involved
immunophenotyping by monoclonal antibodies to
identify the various cell lineages, dual color fluorescence
in situ hybridization (FISH) with x- and y-chromosomespecific
DNA-probes and a proper detection system for a
simultaneous labeling of the bcr/abl locus. A significant
degree of Ch with more than 20% host CD34+
progenitors was found in the early and late (up to 200
days after BMT) posttransplant period. However, only
10% of these cells harbored the bcr/abl translocation
gene. This result fits well with corresponding
molecularbiological findings of so-called minimal
residual disease. Conversion of Ch evolved during
leukemic relapse with 90% host progenitors of which
50% revealed the bcr/abl locus. A Ch of nucleated
erythroid percursors (5%) and CD68+ macrophages (8%)
was expressed to a significantly lower degree. The
slightly increased frequency found in CD61+
megakaryocytes (16%) was probably due to the
polyploid state of these cells. Similar to the CD34+
progenitor cells abrupt changes from donor to host type
was associated with an insidious transformation into
recurrent leukemia. The CD34+ endothelial cells showed
a minor degree of Ch, because donor-derived elements
ranged from 18% to 25%. Leukemic relapse was
characterized by an almost complete conversion of the
endothelial cells to a host type. These findings point
towards a CD34+ progenitor cell origin of the (leukemic)
endothelial cell layer and suggests that their dysfunction
may contribute to an expansion of the neoplastic clone
Regeneration of heart muscle tissue: quantification of chimeric cardiomyocytes and endothelial cells following transplantation
Persuasive evidence has been recently
provided that adult bone marrow (BM) cells exert
greater plasticity than previously assumed. This review
is focused on the quantification of mixed chimerism
(mCh) in the hearts (cardiomyocytes and endothelial
cells) of patients after orthotopic heart to heart
transplantation (HHT) in comparison to full
(unmanipulated) allogeneic BM and peripheral blood
stem cell (PBSC) transplants. Following a sexmismatched
transplantation constellation heart muscle
tissue obtained at autopsy was examined. Evaluation of
mCh was most often performed by immunophenotyping
combined with fluorescence in-situ hybridization (FISH)
applying x- and y-chromosome-specific DNA probes.
When comparing our data with the results of former
studies that were regularly based on the detection of the
y-chromosome alone, the quantity of chimeric
cardiomyocytes after HHT ranged from 0% to 9%. On
the other hand, after full BM transplantats (chimeric)
cardiomyocytes of donor-type origin appeared at an
incidence between 0.23% to 6.4%. These disturbing
inconsistencies were assumed to be related to
methodology: the restriction to the y-chromosome,
disregard of the plane of section (detection sensitivity
ranging between 35% and 67%) and state of tissue
preservation (cadaver hearts). Therefore, when strictly
applying dual color FISH and limiting the recognition of
chimeric cardiomyocytes and endothelial cells to the
presence of two distinctive signals detection sensitivity was significantly enhanced. Contrasting a total
congruence with the genotyping in control specimens of
normal cadaver hearts, a striking disparity in the extent
of mCh was found depending on the different modes of
transplantation. After allografting with PBSC a
considerably low incidence (1.6%) of chimeric
cardiomyocytes was determined contrasting with 5.3% of donor-derived cells after full BM transplants.
Following HHT host-type endothelial cells (16.2 %) of
the intramural and subepicardial vessel walls were more
often encountered than following BM and PBSC
allografting. These findings are in keeping with the
assumption of a sprouting and migration of vascular
structures into the donor heart from the site of surgical
aligment and injury between retained host and donor
atrial walls. When considering the other methods of
transplantation (BM, PBSC) the data on chimeric
endothelial cells support the hypothesis of a common
hemangioblast. Concerning the cardiomyocytes it seems
most reasonable to assume that primitive mesenchymal
stem cells of the BM play a pivotal role in the
development of mCh. This phenomenon is more
extensively expressed than previously expected and may
be related to an enforced repair of the damaged
myocardium during the post-transplant period as the
sequel of myeloablative (cardiotoxic) conditioning
Dualism of mixed chimerism between hematopoiesis and stroma in chronic idiopathic myelofibrosis after allogeneic stem cell transplantation
Scant knowledge exists concerning lineagerestricted
mixed chimerism (mCh) after allogeneic
peripheral blood stem cell transplantation (PSCT) in
patients with chronic idiopathic myelofibrosis (CIMF).
Following a sex-mismatched PSCT, a combined
immunopheno- and genotyping by fluorescence in-situ
hybridization (FISH) was performed on sequential bone
marrow (BM) biopsies at standardized intervals. Results
were compared with PCR analysis of corresponding
peripheral blood samples in five patients. According to
FISH, pretransplant specimens revealed a gender
congruence of more than 99%, while in the first three
months the total BM exhibited a persistent fraction of
host cells (30% to 40%) with a tendency to decline after
about one year. It is noteworthy that the majority of
endothelial cells maintained a recipient origin, whereas
CD34+ progenitors and especially CD61+ megakaryocytes
exhibited only very few host-derived cells. In
keeping with the prevalence of donor cells in the
hematopoietic compartment, PCR analysis of peripheral
blood cells displayed a non-significant degree of mCh.
In conclusion, according to FISH and PCR analysis,
successful PSCT in CIMF results in an almost complete
chimeric (donor-derived) state of the hematopoietic cell
population. The non-transplantable stromal compartment
includes the vascular endothelium with a predominance
of recipient cells. The minimal mCh of this population
implies probably a donor-derived origin (endothelial
progenitor cells)
DISSECTING GENETIC CONTROL OF HLA-DPB1 EXPRESSION AND ITS RELATION TO STRUCTURAL MISMATCH MODELS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION
Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease
Dissecting genetic control of HLA-DPB1 expression and its relation to structural mismatch models in hematopoietic stem cell transplantation
Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease