Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. institutet, 2006. / Härtill 5 uppsatser.

Introdução: O transplante de células tronco hematopoiéticas é capaz de curar as doenças hematológicas. O papel da repopulação linfocitária precoce no período pós transplan te visa combater a células neoplásicas que resistiram ao regime de condicionamento e prevenir as infecções oportunistas graves. Sendo assim, uma contagem elevada de linfócitos no período pós transplante é capaz de reduzir a mortalidade relacionada ao transplante (TRM), melhorar a sobrevida livre de doença e reduzir a taxa de recidiva. Objetivos: Avaliar a recuperação linfocitária precoce no D+21 e D+30 pós transplante correlacionado com a taxa de recidiva da doença de base, mortalidade, sobrevida global e livre de doença. Analisar a freqüência das complicações infecciosas neste período. Métodos: Analisado o número absoluto de linfócitos no D+21 e D+30 pós transplante de células tronco hematopoiéticas. Conforme dados da literatura definiu-se no D+21 e no D+30 aqueles com número absoluto de linfócitos abaixo e acima de 300 e se correlacionou os dados obtidos com a taxa de óbito, taxa de recidiva, sobrevida global em 5 anos, sobrevida livre de doença, em 5 anos, TRM em 100 dias. e mortalidade não relacionada a recaída (NRM). Resultados: Neste estudo foram incluídos 100 pacientes portadores das seguintes neoplasias hematológicas: leucemia mielóide aguda, leucemia linfocítica aguda, leucemias secundárias e síndrome mielodisplásica. Destes, 55 pacientes eram do sexo masculino e 45 do sexo feminino. A média de idade foi de 27,9 anos (mínima 9 meses e máxima 55 anos). A mediana do tempo de seguimento foi de 601 dias (IC 95% 106-1845). A mediana de CD 34 infundidos foi de 4,0 (IC 95% 2,4-5,7) e quanto a origem destas células CD 34 infundidas 85% foram de medula óssea (MO), 12% periférica (PBSC) e 3% sangue de cordão umbilical (SCU). Quanto ao tipo de condicionamento realizado 22% foram não mieloablativos e 78% mieloablativos.A mediana de linfócitos no D+21 foi de 460 (IC 95% 0 - 6250) e no D+30 foi de 760 (IC 95% 40-6370). Com relação a taxa de infecções observou-se que 19% das infecções foram de etiologia viral, 65 % bacteriana e 17% fúngicas. A sobrevida global (OS) em 5 anos foi de 44 % , sobrevida livre de doença (DFS) foi de 37,7% , a mortalidade relacionada ao transplante (TRM) em 100 dias foi de 32,5%. E a mortalidade não relacionada a recidiva (NRM) em 5 anos foi de 40,2%. No desfecho óbito observamos que 69% dos pacientes que foram a óbito no D+21 tinham linfócitos abaixo de 300, e 43,9% tinham linfócitos acima de 300 (p<0,05). Pacientes com valores menores que 300 no dia 30 tem 2,20 vezes o risco de irem a óbito quando comparados com aqueles com valores acima de 300 (IC 95% 1,03-4,69) ajustado para DECH e CD34. Pacientes com valores menores que 300 no dia 30 tem 3,76 vezes o risco de irem a óbito em menos de 100 dias quando comparados com aqueles com valores acima de 300 (IC 95% 1,23-11,46) Conclusões: A reconstituição linfocitária precoce (> 300) no D+21 e no D+30 melhora a sobrevida global e livre de doença, bem como reduz a taxa de recidiva da doença de base e reduz a mortalidade. / Background: The role of repopulating lymphocyte after allogenic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumor cells in the early post transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 and 30 after SCT in predicting transplant outcomes of patients in terms of the risk of transplant related mortality (TRM) recurrence of original disease and risk of opportunistic infections. Objective: Evaluate early lymphocyte recovery on D +21 and D +30 posttransplant correlated with the rate of recurrence of the underlying disease, mortality, overall survival and disease free survival. Analyzed the frequency of infectious complications in this period. Methods: Analyzed the absolute lymphocyte count in the D +21 and D +30 after hematopoietic stem cell transplantation. According to literature data set the we correlate the absolute lymphocyte count in the D +21D +30 below and above 300 these data with the rate of death, relapse rate, overall survival in 5 years, disease-free survival in 5 years , TRM in 100 days and mortality unrelated to relapse (NRM). Results : Included in the study 100 patients with the following hematologic malignancies: acute myeloid leukemia, acute lymphocytic leukemia, secondary leukemia and myelodysplastic syndrome. Of these, 55 patients were male and 45 female. The average age was 27.9 years (minimum 9 months and maximum 55 years). The median follow-up was 601 days (95% CI 106-1845). The CD 34 median that was infused was 4.0 (95% CI 2.4 to 5.7).The source of stem cells infused was 85% of bone marrow (BM), peripheral 12% (PBSC) and 3 % of umbilical cord blood (UCB). Regarding the type of conditioning performed 22% were non myeloablative and 78% of lymphocytes were mieloablativos. The median of absolute lymphocyte count in the D +21 was 460 (95% CI 0 to 6250) and D +30 was 760 (95% CI 40- 6370 ). Regarding the rate of infections were observed 19% viral infections , bacterial in 65% and fungal in 17%. Overall survival (OS) at 5 years was 44%, disease-free survival (DFS) was 37.7%, transplant related mortality (TRM) in 100 days was 32.5%. Non relapsed mortality (NRM) at 5 years was 40.2%. The death rate found that 69% of patients who died at the D +21 had presented lymphocytes count below 300, and 43.9% were above 300 lymphocytes (p <0.05). Patients with counts less than 300 in D+30 presented 2.20 times risk of death when compared with those who presented values above 300 (95% CI 1.03 to 4.69) adjusted for GVHD and CD34. Patients presenting values less than 300 in 30 days have 3.76 times more risk of death in less than 100 days compared with those with values above 300 (95% CI 1.23 to 11.46). Conclusions: The early lymphocyte reconstitution (> 300) in D +21 D +30 improves overall survival and disease-free and reduces the relapse rate of the underlying disease and reduces mortality.

Introdução: O transplante de células tronco hematopoiéticas é capaz de curar as doenças hematológicas. O papel da repopulação linfocitária precoce no período pós transplan te visa combater a células neoplásicas que resistiram ao regime de condicionamento e prevenir as infecções oportunistas graves. Sendo assim, uma contagem elevada de linfócitos no período pós transplante é capaz de reduzir a mortalidade relacionada ao transplante (TRM), melhorar a sobrevida livre de doença e reduzir a taxa de recidiva. Objetivos: Avaliar a recuperação linfocitária precoce no D+21 e D+30 pós transplante correlacionado com a taxa de recidiva da doença de base, mortalidade, sobrevida global e livre de doença. Analisar a freqüência das complicações infecciosas neste período. Métodos: Analisado o número absoluto de linfócitos no D+21 e D+30 pós transplante de células tronco hematopoiéticas. Conforme dados da literatura definiu-se no D+21 e no D+30 aqueles com número absoluto de linfócitos abaixo e acima de 300 e se correlacionou os dados obtidos com a taxa de óbito, taxa de recidiva, sobrevida global em 5 anos, sobrevida livre de doença, em 5 anos, TRM em 100 dias. e mortalidade não relacionada a recaída (NRM). Resultados: Neste estudo foram incluídos 100 pacientes portadores das seguintes neoplasias hematológicas: leucemia mielóide aguda, leucemia linfocítica aguda, leucemias secundárias e síndrome mielodisplásica. Destes, 55 pacientes eram do sexo masculino e 45 do sexo feminino. A média de idade foi de 27,9 anos (mínima 9 meses e máxima 55 anos). A mediana do tempo de seguimento foi de 601 dias (IC 95% 106-1845). A mediana de CD 34 infundidos foi de 4,0 (IC 95% 2,4-5,7) e quanto a origem destas células CD 34 infundidas 85% foram de medula óssea (MO), 12% periférica (PBSC) e 3% sangue de cordão umbilical (SCU). Quanto ao tipo de condicionamento realizado 22% foram não mieloablativos e 78% mieloablativos.A mediana de linfócitos no D+21 foi de 460 (IC 95% 0 - 6250) e no D+30 foi de 760 (IC 95% 40-6370). Com relação a taxa de infecções observou-se que 19% das infecções foram de etiologia viral, 65 % bacteriana e 17% fúngicas. A sobrevida global (OS) em 5 anos foi de 44 % , sobrevida livre de doença (DFS) foi de 37,7% , a mortalidade relacionada ao transplante (TRM) em 100 dias foi de 32,5%. E a mortalidade não relacionada a recidiva (NRM) em 5 anos foi de 40,2%. No desfecho óbito observamos que 69% dos pacientes que foram a óbito no D+21 tinham linfócitos abaixo de 300, e 43,9% tinham linfócitos acima de 300 (p<0,05). Pacientes com valores menores que 300 no dia 30 tem 2,20 vezes o risco de irem a óbito quando comparados com aqueles com valores acima de 300 (IC 95% 1,03-4,69) ajustado para DECH e CD34. Pacientes com valores menores que 300 no dia 30 tem 3,76 vezes o risco de irem a óbito em menos de 100 dias quando comparados com aqueles com valores acima de 300 (IC 95% 1,23-11,46) Conclusões: A reconstituição linfocitária precoce (> 300) no D+21 e no D+30 melhora a sobrevida global e livre de doença, bem como reduz a taxa de recidiva da doença de base e reduz a mortalidade. / Background: The role of repopulating lymphocyte after allogenic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumor cells in the early post transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 and 30 after SCT in predicting transplant outcomes of patients in terms of the risk of transplant related mortality (TRM) recurrence of original disease and risk of opportunistic infections. Objective: Evaluate early lymphocyte recovery on D +21 and D +30 posttransplant correlated with the rate of recurrence of the underlying disease, mortality, overall survival and disease free survival. Analyzed the frequency of infectious complications in this period. Methods: Analyzed the absolute lymphocyte count in the D +21 and D +30 after hematopoietic stem cell transplantation. According to literature data set the we correlate the absolute lymphocyte count in the D +21D +30 below and above 300 these data with the rate of death, relapse rate, overall survival in 5 years, disease-free survival in 5 years , TRM in 100 days and mortality unrelated to relapse (NRM). Results : Included in the study 100 patients with the following hematologic malignancies: acute myeloid leukemia, acute lymphocytic leukemia, secondary leukemia and myelodysplastic syndrome. Of these, 55 patients were male and 45 female. The average age was 27.9 years (minimum 9 months and maximum 55 years). The median follow-up was 601 days (95% CI 106-1845). The CD 34 median that was infused was 4.0 (95% CI 2.4 to 5.7).The source of stem cells infused was 85% of bone marrow (BM), peripheral 12% (PBSC) and 3 % of umbilical cord blood (UCB). Regarding the type of conditioning performed 22% were non myeloablative and 78% of lymphocytes were mieloablativos. The median of absolute lymphocyte count in the D +21 was 460 (95% CI 0 to 6250) and D +30 was 760 (95% CI 40- 6370 ). Regarding the rate of infections were observed 19% viral infections , bacterial in 65% and fungal in 17%. Overall survival (OS) at 5 years was 44%, disease-free survival (DFS) was 37.7%, transplant related mortality (TRM) in 100 days was 32.5%. Non relapsed mortality (NRM) at 5 years was 40.2%. The death rate found that 69% of patients who died at the D +21 had presented lymphocytes count below 300, and 43.9% were above 300 lymphocytes (p <0.05). Patients with counts less than 300 in D+30 presented 2.20 times risk of death when compared with those who presented values above 300 (95% CI 1.03 to 4.69) adjusted for GVHD and CD34. Patients presenting values less than 300 in 30 days have 3.76 times more risk of death in less than 100 days compared with those with values above 300 (95% CI 1.23 to 11.46). Conclusions: The early lymphocyte reconstitution (> 300) in D +21 D +30 improves overall survival and disease-free and reduces the relapse rate of the underlying disease and reduces mortality.

Introdução: O transplante de células tronco hematopoiéticas é capaz de curar as doenças hematológicas. O papel da repopulação linfocitária precoce no período pós transplan te visa combater a células neoplásicas que resistiram ao regime de condicionamento e prevenir as infecções oportunistas graves. Sendo assim, uma contagem elevada de linfócitos no período pós transplante é capaz de reduzir a mortalidade relacionada ao transplante (TRM), melhorar a sobrevida livre de doença e reduzir a taxa de recidiva. Objetivos: Avaliar a recuperação linfocitária precoce no D+21 e D+30 pós transplante correlacionado com a taxa de recidiva da doença de base, mortalidade, sobrevida global e livre de doença. Analisar a freqüência das complicações infecciosas neste período. Métodos: Analisado o número absoluto de linfócitos no D+21 e D+30 pós transplante de células tronco hematopoiéticas. Conforme dados da literatura definiu-se no D+21 e no D+30 aqueles com número absoluto de linfócitos abaixo e acima de 300 e se correlacionou os dados obtidos com a taxa de óbito, taxa de recidiva, sobrevida global em 5 anos, sobrevida livre de doença, em 5 anos, TRM em 100 dias. e mortalidade não relacionada a recaída (NRM). Resultados: Neste estudo foram incluídos 100 pacientes portadores das seguintes neoplasias hematológicas: leucemia mielóide aguda, leucemia linfocítica aguda, leucemias secundárias e síndrome mielodisplásica. Destes, 55 pacientes eram do sexo masculino e 45 do sexo feminino. A média de idade foi de 27,9 anos (mínima 9 meses e máxima 55 anos). A mediana do tempo de seguimento foi de 601 dias (IC 95% 106-1845). A mediana de CD 34 infundidos foi de 4,0 (IC 95% 2,4-5,7) e quanto a origem destas células CD 34 infundidas 85% foram de medula óssea (MO), 12% periférica (PBSC) e 3% sangue de cordão umbilical (SCU). Quanto ao tipo de condicionamento realizado 22% foram não mieloablativos e 78% mieloablativos.A mediana de linfócitos no D+21 foi de 460 (IC 95% 0 - 6250) e no D+30 foi de 760 (IC 95% 40-6370). Com relação a taxa de infecções observou-se que 19% das infecções foram de etiologia viral, 65 % bacteriana e 17% fúngicas. A sobrevida global (OS) em 5 anos foi de 44 % , sobrevida livre de doença (DFS) foi de 37,7% , a mortalidade relacionada ao transplante (TRM) em 100 dias foi de 32,5%. E a mortalidade não relacionada a recidiva (NRM) em 5 anos foi de 40,2%. No desfecho óbito observamos que 69% dos pacientes que foram a óbito no D+21 tinham linfócitos abaixo de 300, e 43,9% tinham linfócitos acima de 300 (p<0,05). Pacientes com valores menores que 300 no dia 30 tem 2,20 vezes o risco de irem a óbito quando comparados com aqueles com valores acima de 300 (IC 95% 1,03-4,69) ajustado para DECH e CD34. Pacientes com valores menores que 300 no dia 30 tem 3,76 vezes o risco de irem a óbito em menos de 100 dias quando comparados com aqueles com valores acima de 300 (IC 95% 1,23-11,46) Conclusões: A reconstituição linfocitária precoce (> 300) no D+21 e no D+30 melhora a sobrevida global e livre de doença, bem como reduz a taxa de recidiva da doença de base e reduz a mortalidade. / Background: The role of repopulating lymphocyte after allogenic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumor cells in the early post transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 and 30 after SCT in predicting transplant outcomes of patients in terms of the risk of transplant related mortality (TRM) recurrence of original disease and risk of opportunistic infections. Objective: Evaluate early lymphocyte recovery on D +21 and D +30 posttransplant correlated with the rate of recurrence of the underlying disease, mortality, overall survival and disease free survival. Analyzed the frequency of infectious complications in this period. Methods: Analyzed the absolute lymphocyte count in the D +21 and D +30 after hematopoietic stem cell transplantation. According to literature data set the we correlate the absolute lymphocyte count in the D +21D +30 below and above 300 these data with the rate of death, relapse rate, overall survival in 5 years, disease-free survival in 5 years , TRM in 100 days and mortality unrelated to relapse (NRM). Results : Included in the study 100 patients with the following hematologic malignancies: acute myeloid leukemia, acute lymphocytic leukemia, secondary leukemia and myelodysplastic syndrome. Of these, 55 patients were male and 45 female. The average age was 27.9 years (minimum 9 months and maximum 55 years). The median follow-up was 601 days (95% CI 106-1845). The CD 34 median that was infused was 4.0 (95% CI 2.4 to 5.7).The source of stem cells infused was 85% of bone marrow (BM), peripheral 12% (PBSC) and 3 % of umbilical cord blood (UCB). Regarding the type of conditioning performed 22% were non myeloablative and 78% of lymphocytes were mieloablativos. The median of absolute lymphocyte count in the D +21 was 460 (95% CI 0 to 6250) and D +30 was 760 (95% CI 40- 6370 ). Regarding the rate of infections were observed 19% viral infections , bacterial in 65% and fungal in 17%. Overall survival (OS) at 5 years was 44%, disease-free survival (DFS) was 37.7%, transplant related mortality (TRM) in 100 days was 32.5%. Non relapsed mortality (NRM) at 5 years was 40.2%. The death rate found that 69% of patients who died at the D +21 had presented lymphocytes count below 300, and 43.9% were above 300 lymphocytes (p <0.05). Patients with counts less than 300 in D+30 presented 2.20 times risk of death when compared with those who presented values above 300 (95% CI 1.03 to 4.69) adjusted for GVHD and CD34. Patients presenting values less than 300 in 30 days have 3.76 times more risk of death in less than 100 days compared with those with values above 300 (95% CI 1.23 to 11.46). Conclusions: The early lymphocyte reconstitution (> 300) in D +21 D +30 improves overall survival and disease-free and reduces the relapse rate of the underlying disease and reduces mortality.

In the United States, individuals of Hispanic ethnicity receive disproportionately lower-quality healthcare. These healthcare disparities exacerbate unequal access to quality healthcare services, including disparities in cardiovascular disease (CVD) and human immunodeficiency virus (HIV) care. Research on the role of ethnicity on the CVD outcomes of people living with HIV (PLWH) has been limited. We hypothesize that immunological (CD4+ cell count) and virological (HIV viral load) control may play a role in the development of acute myocardial infarction (AMI) among PLWH, and that Hispanic ethnicity may worsen these outcomes. To verify our hypotheses, we conducted a retrospective cross-sectional study to investigate the strength and direction of association between CD4+ cell count (immunological cohort, n=513) and HIV viral load (virological cohort, n=261) on AMI among respondents of the All of Us Research Program. Hispanic and non-Hispanic respondents for both cohorts were comparable in terms of demographic characteristics, except for a significantly different distribution by race. While we identified increased proportion of non-Hispanic individuals with AMI in the immunologic (6.0% vs. 1.0%; P=0.04) and virologic (5.8% vs. 0%; P=0.007) cohorts, we were not able to identify CD4+ cell count or viral load as significant predictors significantly increasing the likelihood of AMI. Potential explanations discussed include self-selection bias resulting in incomplete laboratory data and an underpowered sample size. While the sample in this study did not support an increased likelihood of AMI by ethnicity, the results should be interpreted carefully in light of the limitations and the established pathophysiological and epidemiological associations posited, underscoring the importance of future research efforts that better represent ethnic minorities and the associations between HIV infection and CVD.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Source: Masters Abstracts International, Volume: 46-05, page: 2669. Adviser: Jan M. Risser. Includes bibliographical references.

OBJECTIVES: The integrin α4β7 is the gut-homing receptor for lymphocytes. It also is an important co-receptor for human immunodeficiency virus (HIV) via glycoprotein (gp)120 binding. Depletion of gut cluster of differentiation (CD)4 T cells is linked to chronic inflammation in patients with HIV; however, measuring CD4 cells in the gut is invasive and not routine. As such, establishing a peripheral marker for CD4 depletion of the gut is needed. We hypothesized that α4β7 CD4 T cells are depleted in the peripheral blood of treatment-naïve patients with HIV compared with healthy controls. METHODS: The study groups were treatment-naïve patients with HIV and uninfected controls. Subjects were included if they were 18 years or older with no history of opportunistic infections, active tuberculosis, or cancer. We collected peripheral blood and examined on whole blood using flow cytometry for the following cell surface markers: CD4, CD45RO, chemokine receptor type 5, C-X-C chemokine receptor type 4 (CXCR4), and the integrin β7. We collected demographic information, including age, sex, and ethnicity, as well as viral load (VL) and CD4 count. Two-samplettests and Fisher exact tests were used to compare the differences between the two groups. Spearman correlation coefficients were calculated between CD4 count and log10-VL and percentage of CD4+/CD45RO+/β7+and log10-VL in patients. RESULTS: Twenty-two subjects were enrolled in the study (12 patients with HIV and 10 controls). There were no differences in age or sex between the two groups. There were more Hispanics and fewer Asians in the group comprising patients with HIV compared with the control group (7 vs 2 and 0 vs 4,P= 0.05, respectively). Patients infected with HIV had significantly lower frequencies of CD4+/CD45RO+/β7+cells (median 12%, range 5-18 compared with uninfected controls: median 20%, range 11-26,P= 0.0007). There was a statistically significant difference in the percentage of CD4+/CD45RO+/C-X-C chemokine receptor type 4+cells between patients (72%, range 60%-91%) compared with controls (79%, range 72%-94%,P= 0.04). The percentage of CD4+/CD45RO+/chemokine receptor type 5+did not differ between the group of patients with HIV and the control groups (22%, range 11%-57% vs 27%, range 14%-31%;P= 0.8, respectively). There was no correlation between percentage of CD4+/CD45RO+/β+cells and log10-VL as measured by the Spearman correlation coefficient (r= 0.05,P= 0.88) in patients infected with HIV. CONCLUSIONS: Memory CD4 β7+cells are reduced significantly in the peripheral blood of untreated patients infected with HIV, which could be used as a noninvasive indicator of intestinal CD4 T cell loss and recovery. Further studies are needed to examine whether depletion of these CD4+/CD45RO+/β7+cells in the peripheral blood parallels depletion in the gut of treatment-naïve patients with HIV and whether levels return to control levels after treatment.