<h1>Abstract</h1><p><strong>Background: </strong>Pain is usually common patients who undergo high-dose treatment in combination with HSCT. Pain is usually associated with side effects as for example mucositis. The purpose of this study was to examine patients’ experiences of pain in relation to stemcellstransplantation. The purpose was also to examine how patients experience that they have been treated by the personnel regarding their pain, and also if the pain relief correspond to the patients expectations.</p><p><strong>Method: </strong>The study is a descriptive, longitudinal study. Eight patients who underwent HSCT were interviewed. The study implemented in three parts, whereof two interviews and one questionnaire. The interview material was analyzed by means of content analysis.</p><p><strong>Results: </strong>The result shows that five of eight patients experienced pain during HSCT treatment. Three of these informants experienced pain in their mouth, their head and in their stomach. This is usually commonly side effects of the treatment. Back pain occurs in two of the patients and this pain hasn’t proceeded during the treatment.</p><p>Three informants did not experience any pain at all during the time of nursing. The result even shows that the all of the informants had experienced a well refutation of the personnel in terms of their pain. All informants reported that it was important to be well pain relieved. Those informants who had pain during their treatment were very satisfied with the pain relief they have got.</p><p><strong> </strong></p><p><strong>Keywords: </strong>stem cell transplantation, oral pain, pain treatment, oral mucositis, satisfaction with care.</p> / <p> </p><h1>Sammanfattning</h1><p><strong>Bakgrund och syfte: </strong>Smärta är vanligt förekommande bland patienter som genomgår högdosbehandling i kombination med HSCT. Smärta är vanligtvis förknippad med biverkningar som t ex mucosit. Syftet med denna studie var att undersöka patienters upplevelse av smärta i samband med stamcellstransplantation. Syftet är även att undersöka hur patienterna upplever att de blir bemötta av personalen angående sin smärta, samt om smärtlindringen motsvarar patientens förväntningar.</p><p><strong>Metod:</strong> Studien är en deskriptiv, longitudinell studie. Åtta patienter som skulle genomgå stamcellstransplantation intervjuades. Studien genomfördes i tre delar, varav två intervjuer och ett frågeformulär. Intervjumaterialet analyserades med innehållsanalys.</p><p><strong>Resultat:</strong> Resultatet visar att fem av åtta patienter upplevde smärta i samband med HSCT. Tre av dessa informanter upplevde smärtor i munnen, huvudet och i magen. Ryggsmärta förekom hos två av informanterna och denna smärta hade inte uppstått i samband med behandlingen. Tre informanter upplevde ingen smärta alls under hela vårdtiden. Resultatet visar även att samtliga informanter upplevt ett bra bemötande av personalen vad gäller deras smärta. Alla informanter uppgav att det var viktigt att vara bra smärtlindrad. De informanter som hade smärta under behandlingen var mycket nöjda med den smärtlindring de fick.</p><p><strong> </strong></p><p><strong>Nyckelord: </strong>stamcellstransplantation, oral smärta, smärtbehandling, oral mucosit, tillfredsställelse med vård.</p>

<p>In this thesis, the four-color fluorescence tag-microarray minisequencing system pioneered by our group was further developed and applied for analysing genetic variation in human DNA and RNA. A SNP marker panel representing different chromosomal regions was established and used for identification of informative SNP markers for monitoring chimerism after stem cell transplantation (SCT). The success of SCT was monitored by measuring the allelic ratios of informative SNPs in follow-up samples from nine patients with leukaemia. The results agreed with data obtained using microsatellite markers. Further the same SNP marker panel was used for evaluation of two whole genome amplification methods, primer extension preamplification (PEP) and multiple displacement amplification (MDA) in comparison with genomic DNA with respect to SNP genotyping success and accuracy in tag-array minisequencing. Identical results were obtained from MDA products and genomic DNA.</p><p>The tag-microarray minisequencing system was also established for multiplexed quantification of imbalanced expression of SNP alleles. Two endothelial cell lines and a panel of ten coding SNPs in five genes were used as model system. Six heterozygous SNPs were genotyped in RNA (cDNA) from the cell lines. Comparison of the relative amounts of the SNPs alleles in cDNA to heterozygote SNPs in genomic DNA displayed four SNPs with significant imbalanced expression between the SNP alleles. Finally, the tag-array minisequencing system was modified for detection of splice variants in mRNA from five leukaemia cell lines. A panel of 20 cancer-related genes with 74 alternatively splice variants was screened. Over half of the splice variants were detected in the cell lines, and similar alternative splicing patterns were observed in each cell line. The results were verified by size analysis of the PCR product subjected to the minisequencing primer extension reaction. The data from both methods agreed well, evidencing for a high sensitivity of our system.</p>

<p>Treatment results and clinical characteristics in adult acute lymphoblastic leukaemia (ALL) were evaluated regarding three issues: a new treatment with cytarabine up-front, stem cell transplantation and a comparison between adult and paediatric treatment protocols. All studies were conducted on a national basis. Furthermore, activity of imatinib was investigated by in vitro cytotoxicity assay. </p><p>The national protocol was evaluated in 153 adult ALL patients. A high complete remission rate, 86%, was achieved with 29% overall survival at 3-years. Favourable outcome was identified in patients < 40 years with precursor B phenotype and continuous complete remission was higher for precursor B compared to T-ALL. </p><p>Stem cell transplantation was evaluated in 187 patients. No differences in outcome between allogeneic and autologous transplantation were found, with the exception of Philadelphia-positive ALL, in which allogeneic transplantation was preferable. Limited chronic graft-versus-host disease (compared to none) resulted in superior disease free survival. </p><p>The paediatric NOPHO-92 and the Adult protocols were evaluated for 243 ALL-patients. Superior remission rate and survival were achieved for 10-18 year-olds treated according to the Paediatric protocol compared to both 15-25 and 25-40 year-olds treated according to the Adult protocol. Treatment protocol was a significant prognostic factor for patients aged 15-20 years. </p><p>Fluorometric Microculture Cytotoxicity Assey was used to analyze 15 tumour cell samples from ALL patients. High concordance was determined between in vitro sensitivity to imatinib and presence of BCR-ABL. Daunorubicin, prednisolone and cytarabine had the greatest benefit from a combination with imatinib. </p><p>The national adult treatment protocol’s results were consistent with international trials regarding precursor B ALL but may be under performing for T-ALL. Adolescents may benefit from treatment according to the Paediatric protocol. No difference in outcome between allogeneic and autologous stem cell transplantation was determined except for Philadelphia-positive patients, despite the indication of a graft-versus-leukaemia effect.</p>

In this thesis, the four-color fluorescence tag-microarray minisequencing system pioneered by our group was further developed and applied for analysing genetic variation in human DNA and RNA. A SNP marker panel representing different chromosomal regions was established and used for identification of informative SNP markers for monitoring chimerism after stem cell transplantation (SCT). The success of SCT was monitored by measuring the allelic ratios of informative SNPs in follow-up samples from nine patients with leukaemia. The results agreed with data obtained using microsatellite markers. Further the same SNP marker panel was used for evaluation of two whole genome amplification methods, primer extension preamplification (PEP) and multiple displacement amplification (MDA) in comparison with genomic DNA with respect to SNP genotyping success and accuracy in tag-array minisequencing. Identical results were obtained from MDA products and genomic DNA. The tag-microarray minisequencing system was also established for multiplexed quantification of imbalanced expression of SNP alleles. Two endothelial cell lines and a panel of ten coding SNPs in five genes were used as model system. Six heterozygous SNPs were genotyped in RNA (cDNA) from the cell lines. Comparison of the relative amounts of the SNPs alleles in cDNA to heterozygote SNPs in genomic DNA displayed four SNPs with significant imbalanced expression between the SNP alleles. Finally, the tag-array minisequencing system was modified for detection of splice variants in mRNA from five leukaemia cell lines. A panel of 20 cancer-related genes with 74 alternatively splice variants was screened. Over half of the splice variants were detected in the cell lines, and similar alternative splicing patterns were observed in each cell line. The results were verified by size analysis of the PCR product subjected to the minisequencing primer extension reaction. The data from both methods agreed well, evidencing for a high sensitivity of our system.

Abstract Background: Pain is usually common patients who undergo high-dose treatment in combination with HSCT. Pain is usually associated with side effects as for example mucositis. The purpose of this study was to examine patients’ experiences of pain in relation to stemcellstransplantation. The purpose was also to examine how patients experience that they have been treated by the personnel regarding their pain, and also if the pain relief correspond to the patients expectations. Method: The study is a descriptive, longitudinal study. Eight patients who underwent HSCT were interviewed. The study implemented in three parts, whereof two interviews and one questionnaire. The interview material was analyzed by means of content analysis. Results: The result shows that five of eight patients experienced pain during HSCT treatment. Three of these informants experienced pain in their mouth, their head and in their stomach. This is usually commonly side effects of the treatment. Back pain occurs in two of the patients and this pain hasn’t proceeded during the treatment. Three informants did not experience any pain at all during the time of nursing. The result even shows that the all of the informants had experienced a well refutation of the personnel in terms of their pain. All informants reported that it was important to be well pain relieved. Those informants who had pain during their treatment were very satisfied with the pain relief they have got.   Keywords: stem cell transplantation, oral pain, pain treatment, oral mucositis, satisfaction with care. / Sammanfattning Bakgrund och syfte: Smärta är vanligt förekommande bland patienter som genomgår högdosbehandling i kombination med HSCT. Smärta är vanligtvis förknippad med biverkningar som t ex mucosit. Syftet med denna studie var att undersöka patienters upplevelse av smärta i samband med stamcellstransplantation. Syftet är även att undersöka hur patienterna upplever att de blir bemötta av personalen angående sin smärta, samt om smärtlindringen motsvarar patientens förväntningar. Metod: Studien är en deskriptiv, longitudinell studie. Åtta patienter som skulle genomgå stamcellstransplantation intervjuades. Studien genomfördes i tre delar, varav två intervjuer och ett frågeformulär. Intervjumaterialet analyserades med innehållsanalys. Resultat: Resultatet visar att fem av åtta patienter upplevde smärta i samband med HSCT. Tre av dessa informanter upplevde smärtor i munnen, huvudet och i magen. Ryggsmärta förekom hos två av informanterna och denna smärta hade inte uppstått i samband med behandlingen. Tre informanter upplevde ingen smärta alls under hela vårdtiden. Resultatet visar även att samtliga informanter upplevt ett bra bemötande av personalen vad gäller deras smärta. Alla informanter uppgav att det var viktigt att vara bra smärtlindrad. De informanter som hade smärta under behandlingen var mycket nöjda med den smärtlindring de fick.   Nyckelord: stamcellstransplantation, oral smärta, smärtbehandling, oral mucosit, tillfredsställelse med vård.

Bakgrund:Oral mukosit (OM) är en toxisk biverkan efter högdos cytostatikabehandling (HDC) och hematopoietisk stemcellstransplantation (HSCT). OM orsakar kliniska komplikationer samt negativa följder för patienten, som längre sjukhusvistelse, oral smärta, viktförlust och parenteral nutrition (PN).Syfte:Att undersöka om det föreligger skillnad i viktförändring och nutritionsstatus hos patienter som använder munsköljmedlet, Caphosol ® i tillägg till standardbehandling i jämförelse med standardbehandling vid behandling med HDC och HSCT.Metod:En randomiserad kontrollerad öppen studie där patienter &gt; 16 år (n=40), behandlades med HDC, inför HSCT på Akademiska universitetssjukhuset, Uppsala. Patienterna randomiserades, 1:1, till oral standardbehandling och munsköljmedlet Caphosol® (EXP n=20) eller oral standardbehandling (KTR n=20). OM, oral smärta, viktförlust och dagar av PN registrerades och analyserades från baseline till 21 dagar efter avslutad HDC.Resultat:Caphosol ® hade ingen signifikant betydelse för viktförändringar mellan EXP- och KTR-grupperna. OM-smärta debuterade senare i EXP än i KTR-gruppen. KTR gruppen använde mer PN jämfört med EXP-gruppen.Konklusion:Caphosol ® hade obetydlig inverkan på förekomst, duration och svårighetsgrad av OM under HCT vid HSCT och därmed liten effekt på nutrition och vikt. Det förelåg ingen fördel att addera Caphosol ® till oral standardbehandling. / Background:Oral mucositis (OM) is a result of cytotoxic effects of high dose chemotherapy (HDCT) administered before hematopoietic stem cell transplantation (HSCT). It is a source of negative consequences for the patient, such as longer hospitalization, oral pain, weight loss, and use of parenteral nutrition (PN).Objective:To investigate whether there is differences in weight changes and nutritional status in patients receiving mouth rinse, Caphosol®, in addition to standard oral care (OC) compared to standard OC for HDCT and HSCT.Method:A randomized, controlled open study with patients &gt; 16 years, treated with HDCT before HSCT at Akademiska University Hospital, Uppsala, Sweden. Patients randomized 1:1 to standard OC and Caphosol® (EXP, n=20) or standard OC (CTR n = 20). Oral pain, weight loss and days of PN was recorded and analysed from baseline to day 21 post HDCT.Result:Caphosol ® had no significant impact on weight changes between EXP and CTR groups. OM-pain peaked later in the EXP group than in CTR. No significance in weight change between settings. CTR group had higher use of PN compared to EXP.Conclusion:Caphosol® had little effect on frequency, duration and severity of OM and thereby little effect on nutrition and weight. There was no advantage to add Caphosol ® to standard OC.

Thesis (M.S.)--University of South Florida, 2009. / Title from PDF of title page. Document formatted into pages; contains 52 pages. Includes bibliographical references.

CD28 co-stimulation is required for the generation of naturally occurring regulatory T cells (nTregs) in the thymus through Lck-signaling. However, high level of CD28 suppresses the generation of induced Tregs (iTregs) from naïve CD4 T cells, although underlying mechanism(s) has not been defined. Here we investigated the role of CD28-mediated signaling pathways in the suppression of Treg generation. We used a series of transgenic (Tg) mice on CD28-deficient background that bears WT CD28 or mutated CD28 in its cytosolic tail incapable of binding to Lck, PI3K or Itk. Regardless of exogenous IL-2, strong CD28 costimulation suppressed iTreg generation through Lck signaling. Using a GVHD model to test the role of CD28-mediated iTreg suppression in T cell pathogenicity in vivo, we found that CD28-Lck T cells induced significantly less GVHD than T cells from CD28-WT mice. Furthermore, we found that the recipients of T cells from CD28-Lck mice generated significantly more iTregs than those with T cells from CD28-WT, which contribute to reduced graft-versus-host disease (GVHD) development in recipients of CD28-Lck T cells. These results indicate that CD28 costimulation can negatively regulate Treg generation and may provide an avenue for control of T-cell immunity or tolerance by regulating Tregs using the CD28 signal as a target. We went a step forward and investigated the therapeutic potential of antigen-specific iTregs in the prevention of GVHD. Donor hematopoietic stem cells and mature T cells are transplanted into a lymphopenic host to potentially cure many cancers and hematopoietic diseases like leukemia in bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HCT), but the frequent development of GVHD is the main drawback of this treatment. nTregs suppress the development of GVHD and may spare graft-versus-tumor effect. However, nTregs are a minor (~5%) subpopulation of CD4 helper T cells in healthy individuals, and using in vitro expanded nTregs is a common strategy to test their therapeutic potential in BMT. The concern of in vitro expanded nTregs may include their stability of Foxp3 (master regulatory gene for the development and function of regulatory T cell) expression and suppressive function, survival in vivo, and the non-selective suppression of the pre-activated nTregs. Antigen-specific activation of the regulatory T cells is important for optimal function. In this study, we used an alternative strategy to generate antigen-specific, iTregs and assessed their suppressive potential by comparing their effectiveness in preventing GVHD with polyclonal iTregs. We found that antigen-specific iTregs prevented GVHD lethality in recipients that expressed the target antigen, but were not protective of recipients who did not express the target antigen. Furthermore, antigen-specific iTregs were significantly more efficient than those polyclonal Tregs in the prevention of GVHD. These results reveal the therapeutic potential of antigen-specific iTregs to prevent GVHD efficiently and selectively, and provide the rationale to use antigen-specific iTregs in clinical HCT.

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