Bone marrow transplantation (BMT) is the treatment of choice for many malignancies and other childhood disorders. Acknowledging that the entire family is affected when a child undergoes a BMT, increasing research attention has been given to understanding this experience from the perspectives of recipients, parents and the family as a whole. Yet, minimal attention has been directed at understanding the experience of healthy siblings as they transition through the BMT experience. Before intervention studies can be undertaken that will help healthy siblings transition through the BMT experience, knowledge about the impact of the experience on siblings is needed. Accordingly, a qualitative study guided by the philosophy of hermeneutic phenomenology was conducted to elicit detailed descriptions of the lived experience of siblings. Participants were children, adolescents and young adults with a sibling who had undergone a BMT during childhood. Participants were recruited from a pediatric BMT clinic in Western Canada. Semi-structured, open-ended interviews that explored siblings’ memories about what it is like to be a sibling of a child who has had a BMT were conducted with each participant. Demographic data and field notes were recorded. All interviews and field notes were transcribed. The transcripts were reviewed repeatedly for significant statements in an attempt to find meaning and understanding through themes. The data analysis revealed the essence of siblings’ lived experience of transitioning through the BMT trajectory as an interruption in family life. Four themes communicated the essence of siblings’ lived experience: (1) life goes on, (2) feeling more or less a part of a family, (3) faith in God that things will be okay, and (4) feelings around families. Differences between donor and non-donor siblings are highlighted. Siblings’ recommendations for health care professionals are also provided. Results from this study will help health professionals better anticipate the diverse and shifting needs and demands of siblings of pediatric BMT patients. Recommendations for future research and innovations in nursing interventions are provided. / October 2005

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 61-64).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Umbilical cord blood (CB) has been used as a source of haemopoietic stem cells in both related and unrelated bone marrow transplantation and in both settings there appears to be a reduced incidence of graft-versus-host disease (GVHD) when compared to bone marrow transplantation. The aim of this study was to perform a phenotypic and cellular analysis of both cord and adult mononuclear cells <I>in vitro</I> in order to identify any immunological characteristic that could account for the apparent reduced incidence of GVHD observed, <I>in vivo</I>. For this, the cell surface phenotype, allogeneic cellular responses, cytokine secretion and expression of co-stimulatory molecule CD40L was studied. The phenotypic analysis was carried out by determining the proportion of cells expressing the CD4, CD8, CD16, CD19, CD45RA and CD45RO markers using 3 colour flow cytometric analysis. The results showed that in cord blood mononuclear cells, there was an increased number of cells expressing CD19⁺ whereas the number of cells expressing CD8⁺ was decreased compared to adult blood mononuclear cells (ABMNCs). In contrast the number of cells expressing CD4⁺ and CD16⁺ was similar in both cord blood mononuclear cells (CBMNCs) and ABMNCs. Further phenotypic analysis confirmed that cord blood contained primarily 'unprimed' T cells expressing CD45RA, while adult peripheral blood lymphocytes express mainly the CD45R 'memory' phenotype. The primary and secondary allogeneic responses of cord and adult mononuclear cells were assessed using the standard mixed lymphocyte reaction (MLR) and the primed lymphocyte test (PLT), respectively. These results showed that there was no significant difference in primary MLR responses of CBMNCs and ABMNCs. In contrast, CBMNCs had a decreased ability to mount a secondary proliferative response compared to ABMNCs. However this impaired ability to respond could be overcome by the addition of exogenous IL-2 to the cultures. The secretion of cytokines such as IL-2, IL-4, γIFN and TNF-α and the expression of CD40L on PMA- and ionomycin-activated CBMNCs and ABMNCs was also analysed by 3 colour flow cytometry. These results showed that upon activation CBMNCs produced reduced levels of cytokines and had reduced expression of CD40L. It is likely that the reduced cytokine production and CD40L expression observed is due to the predominance of CD45RA⁺ cells in CB compared to AB. In summary, this study has shown that CB and AB have different phenotypic and functional characteristics in vitro which may well explain the reduced incidence of GVHD observed in cord blood transplantation.

Bone marrow transplantation (BMT) is the treatment of choice for many malignancies and other childhood disorders. Acknowledging that the entire family is affected when a child undergoes a BMT, increasing research attention has been given to understanding this experience from the perspectives of recipients, parents and the family as a whole. Yet, minimal attention has been directed at understanding the experience of healthy siblings as they transition through the BMT experience. Before intervention studies can be undertaken that will help healthy siblings transition through the BMT experience, knowledge about the impact of the experience on siblings is needed. Accordingly, a qualitative study guided by the philosophy of hermeneutic phenomenology was conducted to elicit detailed descriptions of the lived experience of siblings. Participants were children, adolescents and young adults with a sibling who had undergone a BMT during childhood. Participants were recruited from a pediatric BMT clinic in Western Canada. Semi-structured, open-ended interviews that explored siblings’ memories about what it is like to be a sibling of a child who has had a BMT were conducted with each participant. Demographic data and field notes were recorded. All interviews and field notes were transcribed. The transcripts were reviewed repeatedly for significant statements in an attempt to find meaning and understanding through themes. The data analysis revealed the essence of siblings’ lived experience of transitioning through the BMT trajectory as an interruption in family life. Four themes communicated the essence of siblings’ lived experience: (1) life goes on, (2) feeling more or less a part of a family, (3) faith in God that things will be okay, and (4) feelings around families. Differences between donor and non-donor siblings are highlighted. Siblings’ recommendations for health care professionals are also provided. Results from this study will help health professionals better anticipate the diverse and shifting needs and demands of siblings of pediatric BMT patients. Recommendations for future research and innovations in nursing interventions are provided.

The aim of this project was to develop an in vitro functional assay for the prediction of allograft rejection following renal transplantation. This assay was also used to study acute GVHD following identical sibling bone marrow transplantation. Lymphocyte cytokine profiles were measured by ELISA (protein secretion) and flow cytometry (cytokine expression) following mitogen stimulation and MLR. In normal individuals, considerable inter-individual variations were found in both protein secretion (IL-2, IL- 4, IL-10 and IFN-γ) and cytokine expression (IL-2 and IFN-γ). Strong relationships were found between IL-2 protein and expression, IL-2 and IL-10 protein, and IL-10 and IFN-γ protein secretion. Analysis of cytokine gene polymorphisms showed no correlation between IFN-y protein secretion, frequency or gene polymorphism. Pre-transplant MLRs were set up between renal transplant patient/donors pairs and cytokine protein secretion (IL-2, IL-4, IL-6, IL-10 and IFN-γ) measured by ELISA. Analysis was performed to ascertain predictive factors of allograft rejection. Inter-individual variations were found for all cytokine profiles. Significant correlations were found between individual cytokine protein profiles including IL-10 and IFN-γ. In addition, a correlation was found between HLA-DR mismatching and both IL-10 and IFN-γ protein secreted in the MLR. Primary univariate analysis revealed that HLA and HLA-DR mismatching, female donor sex, MLR-stimulated IL-10, MLR-stimulated IFN-γ and spontaneous IL-4 secretion were associated with an increased risk of rejection. Multivariate analysis showed the strongest correlations for predicting risk of rejection to be female donor sex, HLA mismatching and MLR-stimulated IL-l 0 secretion. A combination of high HLA mismatching and high IL-l 0 secretion in MLR gave the highest risk of rejection (RR=25.5). Finally, cytokine secretion decreased when measured post-transplant. Prediction of graft survival could not be analysed due to the low number (n=6) of patients that suffered graft failure in the group. Cytokine protein secretion (IL-2, IL-4, IL-10 and IFN-γ) in MLR was also studied for prediction of GVHD after bone marrow transplantation. There was a very low MLR response by all BMT pairs, therefore analysis could not be performed.

Bone marrow transplantation (BMT) is the treatment of choice for many malignancies and other childhood disorders. Acknowledging that the entire family is affected when a child undergoes a BMT, increasing research attention has been given to understanding this experience from the perspectives of recipients, parents and the family as a whole. Yet, minimal attention has been directed at understanding the experience of healthy siblings as they transition through the BMT experience. Before intervention studies can be undertaken that will help healthy siblings transition through the BMT experience, knowledge about the impact of the experience on siblings is needed. Accordingly, a qualitative study guided by the philosophy of hermeneutic phenomenology was conducted to elicit detailed descriptions of the lived experience of siblings. Participants were children, adolescents and young adults with a sibling who had undergone a BMT during childhood. Participants were recruited from a pediatric BMT clinic in Western Canada. Semi-structured, open-ended interviews that explored siblings’ memories about what it is like to be a sibling of a child who has had a BMT were conducted with each participant. Demographic data and field notes were recorded. All interviews and field notes were transcribed. The transcripts were reviewed repeatedly for significant statements in an attempt to find meaning and understanding through themes. The data analysis revealed the essence of siblings’ lived experience of transitioning through the BMT trajectory as an interruption in family life. Four themes communicated the essence of siblings’ lived experience: (1) life goes on, (2) feeling more or less a part of a family, (3) faith in God that things will be okay, and (4) feelings around families. Differences between donor and non-donor siblings are highlighted. Siblings’ recommendations for health care professionals are also provided. Results from this study will help health professionals better anticipate the diverse and shifting needs and demands of siblings of pediatric BMT patients. Recommendations for future research and innovations in nursing interventions are provided.

Thesis (MAppSc (Medical Laboratory Science)) --University of South Australia, 1993

Bibliography: leaves 91-126. / xiv, 126, [61] leaves, [13] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the in-vitro characterisation of residual normal stem cells in the bone marrow (BM) and peripheral blood (PB) at diagnosis in chronic myloid leukaemia (CML). Shows that both the CD34+DR- populations of blood and marrow of patients in early chronic phase CML contain BCR-ABL- preprogenitors and are potential targets for positive selection in an autologous transplant program. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998

Bibliography: leaves 91-126. / xiv, 126, [61] leaves, [13] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the in-vitro characterisation of residual normal stem cells in the bone marrow (BM) and peripheral blood (PB) at diagnosis in chronic myloid leukaemia (CML). Shows that both the CD34+DR- populations of blood and marrow of patients in early chronic phase CML contain BCR-ABL- preprogenitors and are potential targets for positive selection in an autologous transplant program. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998