A aspergilose invasiva (AI) é a infecção por fungos filamentosos mais comum em pacientes imunodeprimidos, especialmente em transplantes de células tronco hematopoiético e neoplasias hematológicas. Objetivo: Geral: Estabelecer a comparação entre a dosagem de Galactomanana (GM), 1,3betaD-glucana (BDG) e dados tomográficos no diagnóstico da AI bem como seu papel no desfecho clínico. Específicos: 1. Verificar a sensibilidade e especificidade dos ensaios de Galactomanana e de 1,3betaD-glucana no soro e lavado broncoalveolar. 2. Comparar os resultados da galatomanana e 1,3betaD-glucana com os dados de imagem em pacientes com suspeita de AI. 3. Verificar a relação entre a evolução dos níveis de GM e desfecho clínico (óbito e sobrevida). Casuística, Materiais e Métodos: Realizou-se um estudo tipo coorte prospectiva, incluindo 398 sujeitos das diversas enfermarias de pacientes imunodeprimidos do HCFMUSP, sendo incluídos dois grupos de pacientes: 202(51%) AI e 198(49%) controles. Resultados: Dos casos, 18 (8,8%) tinham aspergilose provada, 28 (13,7%) provável e 158 possível (77,5%), de acordo a classificação de 2002 EORTC/MSG (European Organization for Research and Treatment of Cancer / Mycoses Study Group). Os sujeitos submetidos ao TCTH eram 42,7%, com neoplasias hematológicas 37%, TOS 9% e outras doenças 11,3%. Os fatores de risco associados ao desenvolvimento da AI foram neutropenia, monocitopenia, uso de corticóide, presença de doença pelo citomegalovírus e rejeição ou doença do enxerto contra o hospedeiro. O fator de risco associado à evolução para o óbito foi a presença de AI. Foram observados bons desempenhos para a GM tanto no soro como no LBA com LR menores que os registrados na literatura. O melhor desempenho da GM no soro para aspergilose+provável ocorreu com LR de 0,35 com sensibilidade-S, especificidade-E, valor preditivo positivo- VPP), valor preditivo negativo-VPN) e área sob a curva-ASC de 54,4%, 73,4%, 50,8%, 76,2% e 0,64, sendo os valores superiores para aspergilose provada tanto na S, como E, VPN. No LBA os valores de S-E-VPP-VPN-ASC para GM para LR de 0,65 para aspergilose provável + provada foram 58,3%, 92,6%, 87,5%,71,4% e 0,75, sendo na aspergilose provada os valores de S, e VPN superiores. Nesta casuística, o melhor desempenho para BDG no soro apontou para uma LR de 100 pg/mL na aspergilose provável+provada, com 54,5%, 73,4%, 50,8% e 76,2%, 0,64 respectivamente para S-E-VPP-VPN-ASC. Para BDG no LBA, a LR na aspergilose provável + provada foi de 140 pg/mL, com os mesmos valores de 46,7%, 76,7%, 70%, 55,6% e 0.62, respectivamente. Conclusão: A GM no LBA e no soro foram úteis no diagnóstico da aspergilose mediante emprego de LR menores, sendo mais sensível na LBA, principalmente em estágios iniciais da forma angioinvasiva. A persistência de GM sérica foi relacionada ao óbito em relação à negativação da mesma. A proporção de concordância entre a TC e os biomarcadores no soro e no LBA variou de 0,5 a 0,6, com pequena concordância na estatística kappa. Excelente concordância foi observada entre dois radiologistas independentes, que analisaram de maneira cega as TC de sujeitos com aspergilose provada. Nesta casuística com inclusão de doenças sistêmicas e endêmicas, a BDG teve baixo desempenho diagnóstico / Invasive aspergillosis (IA) has become the leading infectious cause of death in immunocompromised hosts, particularly in subjects under SCTH and hematologic neoplasias. Objectives: General: To compare the performance of GM and BG tests in serum and bronchoalveolar lavage fluid (BAL) and computer tomography (CT) scans in the diagnosis of IA in immunocompromised hosts as well as their role in the patient outcome. Specific: 1. To analyse the sensitivity and specificity of Galactomannan and 1,3 betaD-glucan assays in the serum and bronchoalveolar lavage. 2. To compare the results of Galactomannan and 1,3betaD-glucan assays with CT scans in patients with invasive aspergilosis. 3. To analyse the relationship between the evolution of galactomannan levels and clinical outcome (death or survival). Patients, Materials and Methods: From December 2008 to March 2013, a prospective cohort of 398 patients from several wards of immunocompromised patients of Hospital das Clínicas, Faculdade de Medicina, University of São Paulo was included classified in two groups of patients: 202 (51%) with invasive aspergillosis (IA) and 198 (49%) control patients. Results: Considering 202 cases, 18(8.8%) were subjects with proven, 28(13.7%) with probable aspergillosis and 156(77.5%), with possible aspergillosis, according to 2002 EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) criteria. The most common underlying disease were: HSCT (42.7%), hematologic malignancy (37%), SOT (9%), or other diseases (11.3%). The main risk factors associated with IA were neutropenia, monocytopenia, patients under corticosterois, presence of CMV disease, and rejection or graft versus host disease. The risk factor associated with death was the presence of invasive aspergillosis. Good performances for serum and BAL GM were registered with lower cutoffs in the present workin relationship to those found in the literature. The best cutoff for proven + probable aspergillosis for serum GM was observed at 0.35 vallue with Sensitivity-S, Specificity-Sp, Positive Predictive value-PPV), Negative Predictive Value-NPV) and AUC of 54.4%, 73.4%, 50.8%, 76.2% and 0.64; the values for proven aspergillosis alone were higher for S, Sp and NPV. On BAL tests for GM (cutoff value of 0.65) in proven+probable aspergillosis we observed 58.3%, 92.6%, 87.5%,71.4%, 0.75, respectively as S-Sp-PPV-NPVAUC; the sensitivity and VPN were higher in proven aspergillosis alone. In this work, the best performance in proven+probable aspergillosis for serum BDG showed 100 pg/ML as cutoff value, with 54.5%, 73.4%, 50.8%,76.2%, 0.64 for S-Sp-PPVNPV- AUC, respectively. For BAL- BDG, the cut off for proven+probable aspergillosis was 140 pg/mL, and we observed 46.7%, 76.7%, 70.0%, 55.,6%, 0.62, respectively for for S-Sp-PPV-NPV-AUC. Conclusion: The serum and BAL GM are useful tests for diagnosis in early stages of angioinvasive form at lower cutoffs; BAL GM is more sensitive. Agreement proportion between CT scan and each biomarker in the serum or BAL ranged from 0.5-0.6, with low ? index. Perfect ? statistic was observed for analysis of CT scan of subjects in proven aspergillosis by two independent radiologists, blinded for diagnosis. Persistence of serum GM was associated to death in relationship with its negativation. BDG test showed low performance in this work, where systemic and endemic diseases were included

padrão utilizado para algumas doenças hematológicas e também na consolidação do tratamento de outras doenças. O aumento da demanda de pacientes que necessitam deste tratamento fez com que fossem criados alguns modelos de transplante ambulatorial. A alta precoce é uma modalidade de transplante em que o paciente recebe alta hospitalar após o regime de condicionamento e infusão das células-tronco hematopoiéticas (CTH) e a continuidade do seu tratamento ocorre em regime ambulatorial. Na área da Enfermagem, o número limitado de estudos científicos relacionados à Assistência de Enfermagem nos pacientes submetidos ao TCTH com alta hospitalar precoce são ainda deficientes. Diante disso, o objetivo deste estudo foi analisar os resultados da alta hospitalar precoce como alternativa viável ao tratamento dos pacientes submetidos ao TCTHa e sua relação com a assistência de enfermagem. MÉTODO: Estudo retrospectivo, quantitativo, descritivo e transversal. Foram analisados prontuários de 112 pacientes consecutivos submetidos ao TCTHa, no período de janeiro a dezembro de 2009. Destes 12 pacientes não receberam alta hospitalar da unidade de internação até o décimo dia após o TCTH (D+10) e, por isso, foram excluídos, restando 100 pacientes. RESULTADOS: A mediana de idade foi de 48,5 anos (19-69 anos). Houve um pareamento não intencional do sexo. Todos os pacientes mobilizaram e coletaram CTH por fonte periférica. Os regimes de condicionamento mais utilizados foram BU12+Mel100 e BEAM 400. As toxicidades atribuídas ao regime de condicionamento foram bem conduzidas no ambulatório, expressa por 10 pacientes que necessitaram de internação, embora um grande número de pacientes da casuística apresentou algum grau de toxicidade. A neutropenia febril esteve presente em 58% dos pacientes até a enxertia medular. Não houve aumento na mortalidade na fase de aplasia medular; dois pacientes foram a óbito por causas infecciosas durante os 60 primeiros dias após o TCTH, sendo que apenas um não apresentava enxertia medular. A mediana de enxertia de granulócitos após o TCTHa com alta hospitalar precoce foi de 12 dias e de plaquetas 15 dias, com mediana de transfusões até a alta do serviço de três concentrados de hemácias e quatro concentrados de plaquetas. Vinte e três pacientes necessitaram de internação hospitalar em algum momento desde a alta hospitalar após o transplante até o momento de sua alta. CONCLUSÃO: A equipe de enfermagem apresenta papel fundamental no contexto da alta hospitalar precoce na conduta e manejo dos pacientes. O Enfermeiro participou na orientação e condutas durante a fase de mobilização, transplante e acompanhamento ambulatorial. A mediana de tempo para enxertia medular foi de 12 dias e durante a fase de aplasia os pacientes evoluíram com baixa internação e infecção. Houve baixa incidência de complicações e internações, sendo a toxicidade ao regime de condicionamento a maior causa de internação. As toxicidades ao regime de condicionamento apresentadas foram bem manejadas em regime ambulatorial também pela Equipe de Enfermagem / The autologous hematopoietic stem cell transplantation (HSCTa) is a standard treatment used for some hematological malignancies and also in consolidating the treatment of other diseases. The increased number of patients who need this treatment leads to new models of outpatient transplant. The early discharge is a type of transplant in which the patient is discharged after the conditioning regimen and infusion of hematopoietic stem cells (HSC) and the continuity of your treatment will occur in outpatient settings. Although the models of outpatient HSCT are well defined, there is few studies and publications that demonstrate the actual results of this modality. In the field of nursing, the limited number of scientific studies related to nursing care in HSCT patients with early hospital discharge are even more deficient. Thus, the aim of this study was to analyze the results of early discharge as a viable alternative to the treatment of patients undergoing HSCTa and its relationship to nursing care. Methods: A retrospective, quantitative, descriptive and cross study was performed. A total of 112 patients initially enrolled, 12 were excluded due to the discharged occurred after than tenth day after HSCTa (D +10) and, therefore, 100 patients were enrolled in the study. Results: The median age was 48.5 years (range: 19-69 years). There was an unintentional pairing of sex. All patients were mobilized and collected by HSC peripheral source. The conditioning regimens were used more BU12 + Mel100 and BEAM 400. The conditioning regimen-related toxicities was well at the clinic, expressed by 10 patients who required hospitalization, although a large number of patients in the sample had some degree of toxicity. Febrile neutropenia was observed in 58% of patients until the marrow engraftment. There was no increase in mortality in bone marrow aplasia phase, two patients (2%) died of infectious causes during the first 60 days after HSCTa, and only one patient showed no engraftment. The median granulocyte engraftment after HSCTa with early hospital discharge was 12 days and platelets 15 days, with a median transfusion until discharge from the service three and four units of blood transfused platelet concentrates. Twenty-three patients required hospitalization at some time from hospital discharge after transplantation until the time of his discharge. Conclusion: The nursing team has key role in the context of early hospital discharge in the conduct and management of patients. The nurse participated in the orientation and conduct during the mobilization phase, and outpatient transplant. The median time to engraftment was 12 days and during the aplasia phase of the patients improved, with low infection and hospitalization. There was a low incidence of complications and hospitalizations, and the toxicity conditioning regimen the leading cause of hospitalization. The toxicities presented to the conditioning regimen were well managed on an outpatient basis also for the Nursing Team

O transplante de células tronco hematopoéticas alogênico e autogênico na leucemia mielóide aguda em primeira remissão completa: analise de 62 pacientes. Os pacientes foram submetidos a transplante de células tronco hematopoéticas alogênico e autogênico. Ao final do estudo estavam vivos no alogênico 43,3% e no autogênico 62,5%. Consolidação intensiva teve melhor sobrevida no alogênico. Os pacientes com DECH aguda grau II tiveram melhor sobrevida. Dois pacientes com DECH crônica extensa morreram. Óbito por infecção ocorreu com maior freqüência no alogênico seguido de recidiva. No autogênico a recidiva foi a principal causa de óbito. Morte por toxicidade ocorreu em 47% dos pacientes que foram a óbito no alogênico e em 8,3% no autogênico. Na analise múltipla de Cox a consolidação intensiva e DECH crônica, tiveram significância. / The allogeneic and autologous hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission: analyses of 62 patients. The patients were submitted to allogeneic and autologous hematopoietic stem cell transplantation. The end of the study were kept alive in allogeneic 43,3% and in autologous 65,2%. Patient in allogeneic who were consolidated had better survival. Patients with acute GVHD grade II had better survival. Two patients with chronic GVHD in intense, died. Infection was the most frequent dead cause in allogeneic following relapse. In autologous the relapse was the principal cause of death. Toxicity occurred in 47% of patients who died in allogeneic and 8,3% in autologous. In cox multiple analyses intensive consolidation and chronic GVHD had significance.

Introdução: No presente estudo foram avaliados biomarcadores na ocorrência de febre em pacientes neutropênicos após transplante de células tronco hematopoiéticas (TCTH). Objetivo: O objetivo principal foi avaliar os valores séricos de biomarcadores: proteína C reativa (PCR), procalcitonina (PCT) e IL-6 (interleucina-6) que possam identificar precocemente infecção em TCTH. Outro objetivo foi fatores de risco para óbito nessa população. Métodos: Os biomarcadores foram avaliados em um estudo prospectivo que incluiu 296 pacientes neutropênicos, submetidos a TCTH autólogo ou alogênico. Os biomarcadores PCT, PCR e IL-6 foram dosados nos seguintes momentos:dia da neutropenia constatada sem febre, evento febril ou hipotermia (T < 35ºC), 24 h após a febre ou hipotermia, 72 horas após a febre ou hipotermia e febre prolongada ou seja 48 horas após a coleta no momento anterior ou na persistência da febre, cinco dias após a coleta no momento anterior. Os dados clínicos e laboratoriais, foram avaliados até a evolução para alta ou o óbito, em uma planilha Excel® 2003 e foram processados pelos programas SPSS e STATA. Os pacientes foram classificados nos seguintes grupos (I- afebril; II- febre de origem indeterminada FOI e III- febre clinica ou microbiologicamente comprovada) em relação a cada marcador estudado (PCT, PCR e IL-6). Foram feitos cálculos para estabelecer área sob a curva ROC, sensibilidade, especificidade, para avaliação da febre e óbito. Para avaliar o desfecho óbito foi realizada análise multivariada com regressão logística stepwise. Resultados: Dos 296 pacientes, 190 apresentaram febre. Duzentos e dezesseis (73%) foram submetidos a transplantes autólogos e 80 (27,0%) alogênicos. Dos 80 casos de TCTH alogênicos 74 (92,6%) eram aparentados e apenas 6 (7,4%) aparentados. Dos 80 casos alogênicos 69 (86,3%) eram fullmatch e 11(13,7%) mismatch. Em relação aos grupos já citados acima, temos a seguinte distribuição: grupo I: 106 pacientes (35,8%); grupo II: 112 pacientes (37,8%) e grupo III: 78 (26,4%). Os valores de média e mediana da IL-6 no momento afebril no grupo I em relação ao grupo II (p = 0,013), apresentando valor significativamente maiores. Os níveis da PCR no grupo I diferiram de forma significativa dos encontrados no grupo III (p < 0,05). Os grupos diferiram em relação aos níveis de IL-6 e de PCR no momento febril. O grupo II apresentou concentrações de IL-6 e de PCR significativamente menores que o grupo III. Os melhores valores de corte de PCT para os momentos de coleta: febre, 24 horas após a febre, 72 horas de febre, e febre prolongada foram respectivamente: 0,32; 0,47; 0,46 e 0,35?g/L. No momento da febre a sensibilidade foi 52,3 e a especificidade 52,6 para o diagnóstico de infecção. Os melhores valores de corte de PCR para os momentos de febre, 24 horas após, 72 horas após e febre prolongada foram, respectivamente: 79, 120, 108 e 72 mg/L. No momento da febre a sensibilidade foi 55,4 e especificidade foi 55,1. Os melhores valores de corte de IL-6 para os momentos de febre, 24 h após, 72 horas após a febre e febre prolongada foram respectivamente: 34, 32, 16 e 9 pg/mL. A sensibilidade e especificidade no momento da febre foram respectivamente: 59,8 e 59,7. Na análise dos três biomarcadores no grupo de pacientes autólogos, verifica-se que só a IL-6 apresenta valores significativos nos momentos iniciais (afebril, febre e 24 horas após a febre). Os seguintes fatores de risco independentes foram identificados na análise multivariada: doador aparentado, doador não aparentado, infecção por Gram-negativo, DHL >= 390 (UI/L), ureia >= 25 (mg/dL) e PCR >= 120 (mg/L). Conclusões: IL-6 e PCR têm associação com diagnóstico precoce de infecção clinica ou microbiologicamente confirmada em neutropenia febril após TCTH. A associação dos três marcadores não apresentou nenhuma vantagem, e não melhorou a acurácia diagnóstica. A IL-6 foi o único biomarcador significativamente associado de forma precoce com infecção quando avaliado apenas pacientes submetidos a TCTH autólogos As variáveis independentes associadas com óbito foram: transplante alogênico, infecção por Gram-negativos, DHL >= 390UI/L no momento da febre e ureia >= 25 mg/dL no momento da febre e PCR >= 120 (mg/L) / Introduction: In the present study, biomarkers were assessed in the occurrence of fever in neutropenic patients upon hematopoietic stem cell transplantation (HSCT). Objective: The main objective was to assess the serum values of biomarkers: C-reactive protein (CRP), procalcitonin (PCT) and IL-6 (interleukin-6) which can early identify infection in HSCT. Another objective was risk factors for death in that population. Methods: The biomarkers were assessed in a prospective study which comprised 296 neutropenic patients submitted to autologous or allogeneic HSCT. The biomarkers PCT, CRP and IL-6 were dosed at the following moments: day of afebrile neutropenia, febrile event or hypothermia (T < 35ºC), 24 h upon fever or hypothermia, 72 hours upon fever or hypothermia and long-standing fever, that is, 48 hours upon the last sampling or at fever persistence, five days upon the last sampling. The clinical and laboratory data were assessed up to the evolution to discharge or death, in an Excel® 2003 spreadsheet and were processed by the SPSS and STATA software. Patients were classified in the following groups (I- afebrile; II- fever of unknown origin FUO and III- clinically or microbiologically proven fever) in regard to each biomarker studied (PCT, CRP and IL-6). Calculations were made to establish the area under the ROC curve, sensitivity, specificity, for the assessment of the evolution and death. In order to assess the death outcome, a multivariate analysis with stepwise logistic regression was conducted. Results: Out of the 296 patients, 190 had fever. Two hundred and sixteen (73%) were submitted to autologous transplantations and 80 (27.0%) to allogeneic ones. Out of the 80 cases of allogeneic HSCT, 74 (92.6%) were related and only 6 (7.4%) were unrelated. Out of the 80 allogeneic cases, 69 (86.3%) were fullmatch and 11(13.7%) were mismatch. In regard to the groups mentioned above, we have the following distribution: group I: 106 patients (35.8%); group II: 112 patients (37.8%) and group III: 78 patients (26.4%). The mean and median values of IL-6 at fever onset in group I in regard to group II (p = 0.013), presenting significantly higher values. The levels of CRP in group I differed significantly from those found in group III (p < 0.05). The groups differed in regard to the levels of IL-6 and CRP at fever onset. Group II presented IL-6 and CRP concentrations significantly lower than group III. The best cut-off values of PCT for sampling: fever onset, 24 hours upon fever, 72 hours of fever, and long-standing fever were, respectively: 0.32; 0.47; 0.46 and 0.35?g/L. At fever onset, sensitivity was 52.3 and specificity 52.6 for infection diagnosis. The best cut-off values of CRP for fever onset, 24 hours upon fever, 72 hours upon fever and long-standing fever were, respectively: 79, 120, 108 and 72 mg/L. At fever onset, sensitivity was 55.4 and specificity was 55.1. The best cut-off values of IL-6 for fever onset, 24 hours upon fever, 72 hours upon fever and long-standing fever were, respectively: 34, 32, 16 and 9 pg/mL. At fever onset, sensitivity and specificity were, respectively: 59.8 and 59.7. In the analysis of the three biomarkers in the group of autologous patients, it is observed that only IL-6 presents significant values at initial moments (afebrile, fever and 24 hours upon fever). The following independent risk factors were identified in the multivariate analysis: related donor, unrelated donor, Gram-negative infection, DHL >= 390 (UI/L), urea >= 25 (mg/dL) and CRP>=120 (mg/L). Conclusions: IL-6 and CRP are associated to the early diagnosis of clinically or microbiologically confirmed infection in post-HSCT febrile neutropenia. The association of the three biomarkers did not present any advantage, nor did it improve diagnostic accuracy. IL-6 was the only biomarker significantly associated at an early stage with infection when assessed only in patients submitted to autologous HSCT. The independent variables associated with death were: allogeneic transplantation, Gram-negative infection, DHL >= 390UI/L at fever onset and urea >= 25 mg/dL at fever onset and PCR >= 120 (mg/L)

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogenic blood stem cell transplantation

Dissertation (Ph.D.)--University of South Florida, 2009. / Title from PDF of title page. Document formatted into pages; contains 164 pages. Includes vita. Includes bibliographical references.

Dissertation (Ph.D.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 187 pages. Includes vita. Includes bibliographical references.

No description available.

Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development of GVHD. When applied to the treatment of autoimmune diabetic NOD mice, a model of type 1 diabetes, stem cell transplantation was able to 3) prevent autoimmune recurrence; and 4) permit curative pancreatic islet transplantation. I first describe a tolerance-based stem cell transplantation protocol that combines sub-lethal irradiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, I established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. All chimeric mice treated with anti-CD154 antibody remained free of graft vs.host disease (GVHD) and accepted donor-origin but not third party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. I conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sub-lethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as two injections of anti-CD154 antibody. I also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts. In order to further reduce the impediments associated with the implementation of allogeneic hematopoietic chimerism as a therapeutic modality, I adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines a donor-specific transfusion (DST) with anti-CD154 antibody to induce peripheral transplantation tolerance. When applied to stem cell transplantation, administration of DST, anti-CD154 antibody, and allogeneic bone marrow led to hematopoietic chimerism and central tolerance with no myeloablation (i.e. no radiation) and no GVHD in 3 different strains of mice. The development of donor-specific tolerance in this system was shown to involve deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the cell transfusion that precedes transplantation need not be of donor-origin, suggesting that both allo-specific and non-allo-specific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance partially impair establishment of chimerism. I conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.

No description available.