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Find video protocols related to scientific articles indexed in Pubmed.
Comparison of algorithms for oral busulphan area under the concentration-time curve limited sampling estimate.
Clin Drug Investig
PUBLISHED: 09-16-2014
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Therapeutic drug monitoring (TDM) of the first dose of busulphan during conditioning prior to allogeneic stem cell transplantation provides the possibility of improving the clinical outcome via dose adjustment of subsequent doses. The plasma area under the concentration-time curve (AUC) for busulphan is generally accepted as the parameter that gives the best exposure estimate; however, the sampling frequency needed for reliable AUC calculation remains controversial. The aim of the present investigation was to develop and evaluate a limited sampling model for oral busulphan.
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Novel method to characterize immune cells from human prostate tissue.
Prostate
PUBLISHED: 08-11-2014
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Benign prostatic hyperplasia (BPH) is the most common benign adenoma and prostate cancer is the most frequent malignancy in men over 50 years of age in the Western world, where it remains a significant health problem. Prostate lesions are known to contain immune cells, which may contribute to the immune control of tumor progression. However, due to their low numbers and restricted access to necessary material it is difficult to isolate immune cells from prostate tissue to characterize their immunological features.
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Second solid cancers after allogeneic hematopoietic cell transplantation using reduced-intensity conditioning.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-12-2014
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We examined risk of second solid cancers after allogeneic hematopoietic cell transplantation (AHCT) using reduced-intensity/nonmyeloablative conditioning (RIC/NMC). RIC/NMC recipients with leukemia/myelodysplastic syndrome (MDS) (n = 2833) and lymphoma (n = 1436) between 1995 and 2006 were included. In addition, RIC/NMC recipients 40 to 60 years of age (n = 2138) were compared with patients of the same age receiving myeloablative conditioning (MAC, n = 6428). The cumulative incidence of solid cancers was 3.35% at 10 years. There was no increase in overall cancer risk compared with the general population (leukemia/MDS: standardized incidence ratio [SIR] .99, P = 1.00; lymphoma: SIR .92, P = .75). However, risks were significantly increased in leukemia/MDS patients for cancers of lip (SIR 14.28), tonsil (SIR 8.66), oropharynx (SIR 46.70), bone (SIR 23.53), soft tissue (SIR 12.92), and vulva (SIR 18.55) and skin melanoma (SIR 3.04). Lymphoma patients had significantly higher risks of oropharyngeal cancer (SIR 67.35) and skin melanoma (SIR 3.52). Among RIC/NMC recipients, age >50 years was the only independent risk factor for solid cancers (hazard ratio [HR] 3.02, P < .001). Among patients ages 40 to 60 years, when adjusted for other factors, there was no difference in cancer risks between RIC/NMC and MAC in leukemia/MDS patients (HR .98, P = .905). In lymphoma patients, risks were lower after RIC/NMC (HR .51, P = .047). In conclusion, the overall risks of second solid cancers in RIC/NMC recipients are similar to the general population, although there is an increased risk of cancer at some sites. Studies with longer follow-up are needed to realize the complete risks of solid cancers after RIC/NMC AHCT.
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General health, symptom occurrence, and self-efficacy in adult survivors after allogeneic hematopoietic stem cell transplantation: a cross-sectional comparison between hospital care and home care.
Support Care Cancer
PUBLISHED: 06-03-2014
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Earlier studies have shown that home care during the neutropenic phase after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically safe, with positive outcomes. However, there have been few results on long-term outcomes after home care. The aims of this study were to compare general health, symptom occurrence, and self-efficacy in adult survivors who received either home care or hospital care during the early neutropenic phase after allo-HSCT and to investigate whether demographic or medical variables were associated with general health or symptom occurrence in this patient population.
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Posaconazole concentrations in human tissues after allogeneic stem cell transplantation.
Antimicrob. Agents Chemother.
PUBLISHED: 06-02-2014
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Few data have been published regarding posaconazole tissue concentrations in humans. We analyzed tissue concentrations in biopsy specimens taken at autopsy from seven patients who received posaconazole prophylaxis because of graft-versus-host disease. The results were compared to plasma concentrations collected before death. Tissue concentrations suggestive of an accumulation of posaconazole were found in the heart, lung, liver, and kidney but not in the brain.
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T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.
Stem Cells Dev.
PUBLISHED: 04-16-2014
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In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a standard protocol. The ?Rec-?J? signal joint TREC was measured with real-time quantitative PCR. Patients were grouped based on malignant disease: chronic myeloid leukemia, chronic lymphatic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS). Patients were further subdivided based on TREC levels below (low-TREC) or above (high-TREC) median at each time point. TREC levels were then correlated to relapse incidence and relapse-free survival (RFS). For patients with AML, low TREC levels 2 months post-transplantation were correlated to high relapse incidence at 5 years (P<0.05). In patients with chronic leukemia, high TREC levels were correlated with improved RFS (P<0.05). For patients with MDS, high TREC levels at 9 months post-transplantation were associated with higher RFS at 5 years (P<0.02) and lower relapse incidence (P<0.02). This study shows the potential use of TREC measurement in blood to predict relapse in patients with AML and MDS after allogeneic hematopoietic stem cell transplantation.
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Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation.
Cytotherapy
PUBLISHED: 04-11-2014
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Umbilical cord blood (UCB) is an alternative graft source for hematopoietic stem cell transplantation and has been shown to give results comparable to transplantation with other stem cell sources. Donor lymphocyte infusion (DLI) is an effective treatment for relapsed malignancies after hematopoietic stem cell transplantation. However, DLI is not available after UCB transplantation.
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Varicella-zoster reactivation after allogeneic stem cell transplantation without routine prophylaxis--the incidence remains high.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-10-2014
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One-year prophylaxis with acyclovir has been shown to effectively prevent varicella-zoster virus (VZV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) in a cohort that underwent transplantation in the beginning of the 2000s. Transplantation procedures have since changed considerably and reduced-intensity conditioning (RIC) is nowadays common. We investigated VZV reactivation without routine prophylaxis in a cohort of HSCT patients, 50% of whom had received RIC. The cumulative 2-year incidence of VZV reactivation was 20.7%. Risk factors in a multivariate analysis were treatment with mesenchymal stromal cells (relative hazard [RH], 1.65; confidence interval [CI], 1.07 to 2.54; P = .02), total body irradiation ?6 Gy (RH, 1.55; CI, 1.14 to 2.13; P = .006), engraftment later than day 16 (RH, 1.46; CI, 1.07 to 2.00; P = .02), and age 0 to 19 years (RH, 1.68; CI, 1.21 to 2.35; P = .002). There was no difference in VZV reactivation between patients receiving myeloablative conditioning or RIC. VZV-related complications occurred in 29% of the patients with reactivation; most common were disseminated disease and postherpetic neuralgia. No single low-risk group for VZV reactivation could be identified. We conclude that VZV reactivation remains common after HSCT and carries a high complication rate, warranting prophylaxis.
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Home care during neutropenia after allogeneic hematopoietic stem cell transplantation in children and adolescents is safe and may be more advantageous than isolation in hospital.
Pediatr Transplant
PUBLISHED: 02-26-2014
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After ASCT, children are isolated in hospital to prevent neutropenic infections. Patients living within two-h drive from the hospital were given the option of treatment at home after ASCT. Daily visits by an experienced nurse and phone calls from a physician from the unit were included in the protocol. We compared 29 children and adolescents treated at home with 58 matched hospital controls. The children spent a median time of 13 days at home (range 2-24 days) and 6 (0-35) days in hospital. The cumulative incidence of acute GVHD grades II-IV was 21% in the home-care children and 39% in the controls (p = 0.1). Chronic GVHD and probability of relapse were similar in the two groups. TRM at five yr was 11% in the home-care patients and 18% in the controls. Overall survival at three yr was 77% and 62%, respectively (p = 0.33). None of the patients died at home. Median costs were 38,748 euros in the home-care patients and 49,282 euros in those treated in the hospital (p = 0.2). We conclude that it is safe for children and adolescents to be treated at home during the pancytopenic phase after ASCT.
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Cyclophosphamide alters the gene expression profile in patients treated with high doses prior to stem cell transplantation.
PLoS ONE
PUBLISHED: 01-01-2014
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Hematopoietic stem cell transplantation is a curative treatment for several haematological malignancies. However, treatment related morbidity and mortality still is a limiting factor. Cyclophosphamide is widely used in condition regimens either in combination with other chemotherapy or with total body irradiation.
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Risk factors for Epstein Barr virus related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.
Haematologica
PUBLISHED: 09-20-2013
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Allogeneic hematopoietic stem cell transplantation is a successful treatment strategy for hematologic malignancies and a variety of genetic and metabolic disorders. In the post-stem cell transplantation period the immune compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus associated post-transplant lymphoproliferative disease can be a life-threatening complication for transplanted patients due to suppressed T-cell mediated immunity. We analyzed possible risk factors associated with post-transplant lymphoproliferative disease in a cohort of over thousand patients. The incidence of post-transplant lymphoproliferative disease was 4%. Significant risk factors identified by multivariate analysis were; Human Leukocyte Antigen-mismatch (p<0,001), serological Epstein-Barr virus mismatch Recipient-/Donor+ (p<0,001), use of reduced intensity conditioning (p=0.002), acute Graft vs. Host Disease grade II to IV (p=0.006), splenectomy pre-transplant (p=0.008) and infusion of mesenchymal stromal cells (0=0.015). The risk of post-transplant lymphoproliferative disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long term survival of patients with post-transplant lymphoproliferative disease is poor despite initial successful treatment. Three-year survival among the 40 patients with post-transplant lymphoproliferative disease was 20% as opposed to 62% among patients without post-transplant lymphoproliferative disease (p<0.001). The study identifies patients at risk for post-transplant lymphoproliferative disease after transplantation in need of preemptive measures.
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Cord blood T cells cultured with IL-7 in addition to IL-2 exhibit a higher degree of polyfunctionality and superior proliferation potential.
J. Immunother.
PUBLISHED: 09-03-2013
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One disadvantage with umbilical cord blood transplantation is that donor lymphocyte infusion (DLI) for treatment of threatening rejection or relapse of underlying malignant disease is not available. We have previously expanded T cells from the cord blood graft in clinical setting using anti-CD3/CD28 paramagnetic beads and interleukin (IL)-2 for possible future DLI. Here we studied the effect of adding clinical-grade IL-7 to the expansion protocol. T cells were positively selected with anti-CD3/CD28 paramagnetic beads and cultured in increasing concentrations of IL-2 with and without IL-7 (20 ng/mL). After 7 days of expansion, the T cells were analyzed for proliferative capacity and investigated with flow cytometry and Luminex to determine phenotype, cytokine production, and responsiveness to mitogenic stimulus. Cultures with IL-7 had significantly greater proliferation rate, higher CD4/CD8 ratio, a lower percentage of central memory T cells (CD45ROCCR7), and a higher percentage of effector memory T cells (CD45ROCCR7). We assessed the production of IL-2, tumor necrosis factor-?, interferon-?, and CD107a and found a higher percentage of polyfunctional T cells (positive for 3 to 4 factors) in cells cultured with IL-7. The addition of IL-7 gives a proliferative advantage, also in cultures with a lower dose of IL-2. This could prove advantageous in T-cell culture for adoptive transfer to decrease the risk of apoptosis and other negative effects of cytokine deprivation in vivo. Addition of IL-7 also had an effect on the differentiation status of the cord blood-derived T cells. T cells cultured in IL-7 had more polyfunctional traits, possibly increasing the activity of a putative future umbilical cord blood DLI.
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Reduced IL-7 Responsiveness Defined by Signal Transducer and Activator of Transcription 5 Phosphorylation in T Cells May Be a Marker for Increased Risk of Developing Cytomegalovirus Disease in Patients after Hematopoietic Stem Cell Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-18-2013
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Cytomegalovirus (CMV) reactivation may lead to CMV disease associated with high morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT); the identification of clinically relevant markers may aid in the identification of patients at increased risk for developing CMV-associated complications. We evaluated the phosphorylation of signal transducer and activator of transcription 5 (STAT5) in CD4(+) T cells, CD8(+) T cells, and TCR?? T cells in response to stimulation with IL-7 or IL-2 after HSCT by analyzing blood samples taken monthly 1 to 6 months after HSCT. Patients were monitored weekly with a quantitative PCR from the time of engraftment for CMV viral load in whole blood until at least day 100 after HSCT. We identified a correlation between clinical outcome regarding CMV replication and the ability to respond to IL-7 and IL-2 defined by STAT5 phosphorylation (pSTAT5). Patients with recurrent or prolonged CMV replications had significantly lower pSTAT5 upon stimulation of T cells with either IL-7 or IL-2 at time points 1 through 3 than those without CMV replication (P < .05). This was also found after stimulation of CD8(+) T cells at time point 2 (P < .05). We conclude that reduced responses to IL-7, reflected by pSTAT5, may represent a clinically relevant functional biomarker for individuals at increased risk for CMV reactivation; our data may also aid in designing better strategies to improve anti-CMV immune responses without increasing the risk of developing graft-versus-host disease.
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Improved survival with ursodeoxycholic Acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-23-2013
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We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation.
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Analysis of Donor and Recipient ABO Incompatibility and Antibody-Associated Complications after Allogeneic Stem Cell Transplantation with Reduced-Intensity Conditioning.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-30-2013
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Allogeneic hematopoietic stem cell transplantation (ASCT) can be performed across the ABO blood group barrier. The impact of ABO incompatibility on clinical outcome is controversial. A retrospective analysis of 310 patients who underwent ASCT with reduced-intensity conditioning between 1998 and 2011 was performed to investigate the frequency and clinical implications of anti-RBC antibodies in passenger lymphocyte syndrome (PLS) after minor ABO mismatch (mm), persistent or recurring recipient type ABO antibodies (PRABO) after major ABO mm ASCT, and autoimmune hemolytic anemia (AIHA). Transplantation characteristics and clinical outcome were analyzed by univariate and multivariate analysis for groups with or without anti-RBC antibodies. ABO blood group incompatibility did not affect clinical outcome despite an increased requirement of blood transfusion. Twelve patients with AIHA, 6 patients with PLS, and 12 patients with PRABO post-ASCT were identified. AIHA did not affect overall survival (OS) or transplant-related mortality (TRM), but patients with AIHA had a lower incidence of grades II to IV acute graft-versus-host disease (P = .05). OS in the PLS group was 0% compared with 61% in the whole group receiving minor ABO mm transplants (P < .001). Comparing PRABO patients with those receiving a major ABO mm ASCT, the OS was 17% versus 73% (P = .002) and TRM was 50% versus 21% (P = .03). At our center, PLS after minor ABO mm and PRABO antibodies after major ABO mm ASCT are significant risk factors for decreased OS and TRM. Our results suggest that occurrence of unexpected ABO antibodies after ASCT warrant a wider investigation individual to find the underlying cause.
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A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors.
Clin Transplant
PUBLISHED: 05-22-2013
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The study included 110 consecutive patients with hematological malignancies receiving fludarabine-based reduced intensity conditioning (RIC) and hematopoietic stem cell transplantation (HSCT) from matched unrelated donors. The median age was 55 yr (range 11-68) and all but 15 patients received peripheral blood stem cell grafts. Antithymocyte globulin (ATG) (Thymoglobulin, Genzyme) at a total dose of 6 mg/kg (n = 66) or 8 mg/kg (n = 44) was given to all patients according to protocol. The ATG dose did not affect time-to-neutrophil or platelet engraftment. The incidences of acute GVHD grades II-IV were 34% and 18% (p = 0.11) and of chronic GVHD were 40% and 26% (p = 0.46) in patients receiving 6 and 8 mg/kg of ATG, respectively. The five-yr relapse-free survival (RFS) was 61% and 36% (p = 0.14) in patients, given low and high ATG dose, respectively. In patients given low-dose ATG, the incidence of relapse was lower compared to those given high-dose ATG, 19% vs. 41% (p = 0.04). In multivariate analysis, age >50 yr (p < 0.001), absence of acute (p < 0.001) and chronic GVHD (p = 0.001) were correlated to relapse, and low-dose ATG was associated with improved RFS (p < 0.05). A high dose (8 mg/kg) of ATG in RIC HSCT with unrelated donors increased the risk for relapse and reduced the RFS.
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Systems level immune response analysis and personalized medicine.
Expert Rev Clin Immunol
PUBLISHED: 04-06-2013
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The immune system is an anatomically structured, orchestrated interaction of different cell types that communicate via a large number of receptors recognizing both soluble and cellular ligands. Recent technological advances now allow large-scale measurements for better appreciation of this complexity. Despite these advances, only a few immunological parameters are routinely measured in clinical practice. The authors believe that these measurements are insufficient to describe the immune function of individual patients and thus cannot be used to evaluate immune-mediated diseases or response to therapy. Our current knowledge of immunology comes largely from work in murine model systems where the immune system has been characterized in great detail. This impressive volume of knowledge has proven to be difficult to translate into novel therapies in humans; one reason for this is the lack of large-scale immune monitoring allowing for systems-wide analysis of the human immune system. The authors propose a systems approach to immunology, where the focus is moved from analysis of individual cell types towards more integrated studies of the entire immune system. Exercising systems immunology in preclinical research, during drug development and in patients undergoing therapies affecting the immune system, will enable us to improve clinical results through personalized medicine and help to define clinically relevant patterns of immune reactivity.
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Chimerism patterns of long-term stable mixed chimeras posthematopoietic stem cell transplantation in patients with nonmalignant diseases: follow-up of long-term stable mixed chimerism patients.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-19-2013
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Long-term stable mixed chimerism (MC) is a rare phenomenon after hematopoietic stem cell transplantation (HSCT) characterized by 5% to 95% residual recipient hematopoietic cells. The underlying mechanisms of MC are largely unknown. In this study we compared full donor chimerism with long-lasting stable MC for a median of 9.5 years (range, 5 to 16.5) post-HSCT in patients with nonmalignant diseases. Several factors significantly associated with the likelihood of stable MC development were identified by univariate analysis, eg, younger donor age, sibling donor, and conditioning regimen. Despite a limited patient cohort, our multivariate analysis could confirm that a sibling donor was associated with stable MC development. Furthermore, development of acute-graft-versus-host disease and blood stream infection was significantly more prevalent in the full donor chimerism patient group. Additionally, significant fluctuations in the recipient-to-donor chimerism ratio decreased over time after HSCT in MC patients.
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Hospital care or home care after allogeneic hematopoietic stem cell transplantation--patients experiences of care and support.
Eur J Oncol Nurs
PUBLISHED: 01-21-2013
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Treatment at home during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation (HSCT) has been an option for patients at our center since 1998. Earlier studies have shown that home care is safe and has medical advantages. In this study, we present patients experiences of care and support while being treated in hospital or at home during the acute post-transplantation phase.
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Fetal membrane cells for treatment of steroid-refractory acute graft-versus-host disease.
Stem Cells
PUBLISHED: 01-12-2013
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The placenta protects the fetus from the mothers immune system. We have previously found that fetal membrane cells (FMCs) isolated from term placenta prevent alloreactivity in vitro. FMCs share many features with bone marrow-derived mesenchymal stromal cells (MSCs), which we previously introduced to treat severe acute graft-versus-host disease (GVHD). Here, we tested FMCs for treatment of steroid-refractory acute GVHD. After two passages in culture, approximately 10(9) FMCs were obtained from one single placenta, although not all cells from passage 0 and passage 1 were used for expansion. The FMCs were positive for CD29, CD44, CD73, CD90, CD105, and CD49d but were negative for hematopoietic, endothelial, and epithelial markers. Microsatellite polymorphism analysis showed that FMCs were of maternal origin. All FMCs used showed normal karyotype. Nine patients who had undergone hematopoietic stem cell transplantation (HSCT) and who had developed steroid-refractory grade III-IV acute GVHD were given 0.9-2.8 × 10(6) FMCs per kg at 15 infusions. Median age was 57 years. There was no toxicity from infusion of FMCs in eight patients. One patient had seizures after infusion. Two of eight evaluable patients had a complete response and four had a partial response, giving an overall response rate of 75%. Two patients showed no response at all. Three patients are alive from 6 to 21 months after HSCT. One patient is well and two have chronic GVHD. Thus, FMCs may be successfully used for immune modulation and tissue repair.
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Chimerism and use of mesenchymal stem cells in umbilical cord blood transplantation.
Chimerism
PUBLISHED: 01-01-2013
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We performed a retrospective single-center analysis of 50 umbilical cord blood transplantations (UCBTs), focusing on chimerism development. Complete donor chimerism (DC) was associated with acute graft-vs.-host disease (aGVHD) grades II-IV for the CD3 (+) cell lineage (p = 0.01) and, in multivariate analysis, with total body irradiation (TBI) for all lineages (p < 0.01). Overall survival (OS) was negatively associated with patient age, (p < 0.001); aGVHD grades III-IV, (p < 0.001); and treatment with mesenchymal stem cells (MSCs) (p = 0.027). In conclusion, though multiple factors may have contributed, the association of TBI and DC might be worthy of consideration in the treatment of patients with malignant disease in the UCBT setting. The negative influence of MSCs on OS may be a reason for more careful usage of this treatment modality in combination with UCBT.
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Mesenchymal stem cells inhibit thymic reconstitution after allogeneic cord blood transplantation.
Stem Cells Dev.
PUBLISHED: 10-12-2011
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Cord blood (CB) as a source of stem cells has been a successful addition to the field of allogeneic stem cell transplantation (ASCT). The increased human leukocyte antigen (HLA) permissiveness of CB grafts has made it possible for more patients to undergo treatment. The drawback is that patients suffer from a longer period of compromised immunity. We analyzed T-cell receptor excision circles (TRECs), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels after cord blood transplantation (CBT) in 50 patients transplanted at our center. These immunological parameters were compared retrospectively with clinical factors and complications. We found that TREC levels after CBT were lower in adults, patients with myeloablative conditioning, and in patients with a lower nucleated cell dose in the graft. In addition mesenchymal stem cells (MSC) as co-infusion at the time of CBT had a negative effect on TREC reconstitution. This was found to be associated with decreased overall survival for this patient category. Reduced IgM and IgG levels post-CBT were associated with a major AB0 mismatch, and infusion of MSCs. Our results highlight the importance of close monitoring of the immune reconstitution after CBT. In addition it shows a potentially new suppressive effect of MSCs on the immune system.
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Sirolimus and tacrolimus as immune prophylaxis compared to cyclosporine with or without methotrexate in patients undergoing allogeneic haematopoietic stem cell transplantation for non-malignant disorders.
Eur. J. Haematol.
PUBLISHED: 10-02-2011
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For prevention of graft-versus-host disease (GVHD), treatment of 24 haematopoietic stem cell transplantation (HSCT) patients with sirolimus and tacrolimus was compared to treatment of matched controls with cyclosporine-based regimens. The patients mainly had non-malignant disorders. Two-thirds of the donors were unrelated, and bone marrow was the most common source of stem cells. Rejection occurred in four patients in the sirolimus group and three in the control group. Donor chimerism for CD3, CD19 and CD33 was similar in the two groups. The cumulative incidence of grade II acute GVHD was 22% in the sirolimus patients and 17% in the controls (P=0.78). No patients developed acute GVHD of grades III-IV. The cumulative incidence of chronic GVHD was 25% and 37% in the two groups, respectively (P=0.40). Two patients in the sirolimus group developed Epstein-Barr virus lymphoma, and none in the controls. Side effects and toxicity were similar in the two groups. There was no transplant-related mortality at 5 yr in the sirolimus group, as opposed to 8% in the controls (P=0.47). Survival at 5 yr was 95% and 92%. Thus, sirolimus combined with tacrolimus is a promising immunosuppressive regimen in HSCT, also for non-malignancies, and its efficacy should be confirmed in prospective clinical trials.
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Thymic function after allogeneic stem cell transplantation is dependent on graft source and predictive of long term survival.
Clin. Immunol.
PUBLISHED: 09-14-2011
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T-cell deficiency after allogeneic stem cell transplantation (ASCT) is common and has major impact on clinical outcome. In this retrospective study 210 patients were analyzed with regards to levels of T-cell receptor excision circles (TRECs) during the first 24 months after transplantation. We could for the first time show a significant correlation between the use of bone marrow grafts and higher TREC levels >6 months post-ASCT (p<0.001). Treatment with anti-thymocyte globulin was correlated with lower TREC levels ?6 months post-ASCT (p<0.001). Patients with TREC levels above median at 3 months had a superior overall survival, 80% vs. 56% (p=0.002), and lower transplantation-related mortality, 7% vs. 21% (p=0.01). We conclude that graft source and conditioning regimen may have a significant effect on T-cell reconstitution after ASCT and can thus affect outcome. These results strongly support the use of TREC measurement as part of the standard repertoire of immunological monitoring after ASCT.
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WITHDRAWN: Treatment with mesenchymal stromal cells does not improve long-term survival in patients with severe acute GVHD.
Transpl. Immunol.
PUBLISHED: 07-11-2011
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This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Immune modulation to prevent antibody-mediated rejection after allogeneic hematopoietic stem cell transplantation.
Transpl. Immunol.
PUBLISHED: 05-04-2011
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It has been shown that antibodies to donor CD34+/VEGFR-2+ stem cells or antibodies against mismatched HLA are associated with graft rejection after hematopoietic stem cell transplantation (HSCT). CD34/VEGFR-2 positive stem cells have been implicated to play a major role in engraftment after HSCT. In this study we treated four patients with an imminent risk of antibody-mediated rejection with immune modulation, i.e. plasma exchange, intravenous immunoglobulin (IVIG), and rituximab before HSCT. Three of the patients had been previously transplanted and rejected their initial grafts after 12 months, 1 month, and less than 1 month, respectively. The fourth patient was not transplanted previously but had HLA directed antibodies present against the graft. During the immune modulatory treatment we followed the pattern of antibodies in sera using FACS and microcytotoxicity assay. We could show that two patients had antibodies against donor CD34+/VEGFR-2+ cells while the other two had antibodies directed against HLA. All four patients tolerated the immune modulatory regimen without any side effects. In this preliminary study we show that immune modulatory treatment may be used to reduce antibody levels and to prevent rejection after HSCT. In two of the three patients which experienced previous rejections and had detectable anti-HLA or anti-CD34+/VEGFR-2+ antibodies, immune modulation resulted in engraftment. In the fourth patient with known anti-HLA-class I antibodies, the treatment also resulted in engraftment. Our results encourage further studies regarding this treatment regimen.
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-07-2011
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We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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Second allogeneic hematopoietic stem cell transplantation: a treatment for graft failure.
Clin Transplant
PUBLISHED: 10-14-2010
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We evaluated the results in 20 recent patients treated with a second hematopoietic stem cell transplantation (HSCT) after graft failure (GF). There were 10 children <18 yr of age. Ten patients had a non-malignant disease, and the other 10 had a malignant disease. In most of the transplantations, fludarabine-based reduced intensity conditioning (RIC) was given. Bone marrow was given to 11 patients, peripheral blood system cell (PBSC) in seven and cord blood to two patients. For the second transplantation (n = 20), a new donor was used in nine cases, while the initial donor was used in 11 transplants. Eight patients (40%) suffered from a second GF. Five of these patients were treated with a third HSCT. The probability of survival was 65% one yr and 60% three yr after the second HSCT. No difference in survival was found between patients transplanted with a new donor (56%) compared to those using the original donor (64%). The three-yr survival was 70% for children compared to 50% for adults (p = ns). Patients with a non-malignant disorder showed a three-yr survival of 90% compared to 20% in patients with a malignant disease (p = 0.005). We concluded that re-transplantation using RIC is a valid option for GF, especially in patients with non-malignant disorders.
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Stable mixed double donor chimerism: Absence of war doesnt necessarily mean peace.
Chimerism
PUBLISHED: 09-20-2010
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Double cord blood transplantation has successfully been introduced to remedy the obstacle of a limited stem cell dose in a single cord blood graft. After a short initial period, the sustained hematopoiesis is derived almost exclusively from one of the donated units. In a recent publication in Clinical and Experimental Immunology we investigated two rare individuals in which both cord blood units co-existed for more than two years after transplantation.
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Granulocyte colony-stimulating factor induced acute and chronic graft-versus-host disease.
Transplantation
PUBLISHED: 09-04-2010
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A recent experimental study in mice shed new light on the controversy as to whether granulocyte colony-stimulating factor (G-CSF) increases graft-versus-host disease (GVHD). Total body irradiation and bone marrow were found to be prerequisites for acute GVHD. This study encouraged us to perform a retrospective clinical study.
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Donor lymphocyte infusion may reduce the incidence of bronchiolitis obliterans after allogeneic stem cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 07-19-2010
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Bronchiolitis obliterans (BO) is a serious pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the diagnostic methods used, the incidence of BO, risk factors, and outcome in patients with BO at our center. The study included 527 HSCT patients transplanted between 1995 and 2003. Lung function tests (n = 1177) and risk factor analyses were performed in all patients. Chest X-rays and high-resolution tomographies were investigated in patients with BO. The incidence of BO was 4.8%, as the diagnosis was established in 25 patients (4 children). Median time between HSCT and diagnosis of BO was 356 (84-1823) days. Eight patients (32%) had radiologic changes consistent with BO. Forced expiratory volume for 1 second (FEV(1)) and forced expiratory flow at 50% (FEF(50)) and 75% (FEF(75)) of forced vital capacity (FVC) produced median values that were 49%, 25%, and 18% of the reference values at the time of BO diagnosis. FEF(75) was reduced before BO diagnosis in 7 patients (28%). In a multivariate risk factor analysis, chronic graft-versus-host disease (cGVHD) was found to be associated with BO (P < .001), whereas donor lymphocyte infusion (DLI) diminished the risk (P = .02). For 10 patients with late BO (>1 year after HSCT), 80% survived 5 years after diagnosis, compared to 38% survival in 15 patients with early-onset BO (P = .06). We conclude that lung function tests with a persistent decrease in FEV(1) were more important than radiographic methods to recognize and monitor BO, that FEF(75) may serve as an early warning of BO, and that late-onset BO appears to be associated with better outcome. Chronic GVHD was confirmed as a risk factor, and administration of DLI may diminish the risk.
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C-reactive protein levels before reduced-intensity conditioning predict outcome after allogeneic stem cell transplantation.
Int. J. Hematol.
PUBLISHED: 03-09-2010
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The prognostic value of CRP levels before conditioning for allogeneic stem-cell transplantation (ASCT) was evaluated. Reduced-intensity conditioning (RIC) was given to 205 patients and conventional myeloablative conditioning (MAC) to 299 patients. Most patients had an HLA-compatible related or unrelated donor. There were 287 males and 216 females, median age 36 (1-69) years. Most patients received peripheral blood stem cells. Increased CRP levels (>10 mg/L) were detected in 129 patients (26%). Overall survival (OS) and transplant-related mortality (TRM) were worse for RIC patients with elevated CRP (67 vs. 43%, p = 0.005, and 16 vs. 30%, p = 0.036) while no difference was seen in MAC patients. An infection at the start of conditioning was seen in 27 RIC patients. We identified a subgroup of patients with an infection and elevated CRP (n = 16) and these patients had the worst outcome. In multivariate analysis, both infection and elevated CRP was the strongest factor associated with OS (HR 3.27, p < 0.001) and TRM (HR 4.35, p < 0.001). No correlation between any outcome variable and CRP was seen in MAC-treated patients. CRP may be a good prognostic factor for outcome after RIC and ASCT. It should be analyzed before conditioning, especially in patients with coexisting infection since patients with increased CRP and infection seem to have a very poor outcome after ASCT.
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Leukemia lineage-specific chimerism analysis and molecular monitoring improve outcome of donor lymphocyte infusions.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-18-2010
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A retrospective analysis was performed of 118 patients with hematologic malignancies who received donor lymphocyte infusions (DLIs) after allogeneic stem cell transplantation (ASCT). Treatment was either given because of hematologic relapse (n = 44), molecular/cytogenetic relapse (n = 52), or other causes (n = 22). Molecular relapse was in most cases based on leukemia lineage-specific chimerism analysis. Patients with acute leukemia and myelodysplastic syndrome showed a 3-year survival of 42% if DLI treatment was given because of molecular relapse, compared to 16% in hematologic relapse (P < .006). In multivariate analysis, there was a correlation between response to DLI and nonhematologic relapse (risk ratio [RR] 3.36, P = .001), chronic graft-versus-host disease (cGVHD) (RR = 1.51, P = .005), and late relapse (RR = 2.06, P = .017). The overall incidences of acute GVHD (aGVHD) grades I-II and grades III-IV aGVHD were 33% and 8.5%, respectively. Probability of cGVHD was 33%. The development of aGVHD or cGVHD did not significantly influence the response of DLI in patients with molecular/cytogenetic relapse. However, the development of cGVHD was significantly associated with a better response in patients with hematologic relapse because only 4 of 29 patients without cGVHD responded compared to 7 of 12 with cGVHD (P = .007). The development of cGVHD increased significantly if DLI was given >12 months after ASCT (46% versus 27%, P = .04). In contrast, time between ASCT and start of DLI treatment had no significant influence on the risk of developing aGVHD. To conclude, monitoring of leukemia lineage-specific chimerism is of utmost importance for DLI response after ASCT.
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GVHD prophylaxis using low-dose cyclosporine improves survival in leukaemic recipients of HLA-identical sibling transplants.
Eur. J. Haematol.
PUBLISHED: 11-30-2009
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Graft-versus-host disease (GVHD) prophylaxis of short duration (6 months) with low-dose cyclosporine A (CsA) starting at 1 mg/kg per day i.v. and four doses of methotrexate (MTX) were given to 171 consecutive leukaemic recipients of HLA-identical sibling transplants. In contrast, apart from MTX, retrospective controls received high-dose CsA, starting at 5-7.5 mg/kg per day i.v. and discontinued 1 yr post-transplant. In the low-dose CsA group, the probability of acute GVHD grades I-II (70% vs. 53%, P < 0.01), and chronic GVHD were increased (58% vs. 25%, P < 0.01), whereas the incidences of acute GVHD grades III-IV (9% vs. 5%, P = 0.62), and non-relapse mortality (20% vs. 22%, P = 0.58) were similar. Moreover, the probability of relapse was decreased (31% vs. 54%, P < 0.01), and both relapse-free (56% vs. 38%, P = 0.04) and overall survival (61% vs. 40%, P = 0.04) were markedly improved using the low-dose CsA regimen. In multivariate analyses, low-dose CsA was strongly associated with chronic GVHD [relative hazard (RH) 2.56, P < 0.01], which decreased the risk of relapse (RH 0.46, P < 0.01) and improved the probability of survival (RH 1.84, P < 0.01). In conclusion, a low-dose CsA regimen in leukaemic recipients of HLA-identical sibling transplants increases the rate of chronic GVHD, which seems to attenuate the risk of relapse, thereby improving patient survival owing to enhanced graft-versus-leukaemia effect.
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Respiratory syncytial virus infection in recipients of allogeneic stem-cell transplantation: a retrospective study of the incidence, clinical features, and outcome.
Transplantation
PUBLISHED: 11-26-2009
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Respiratory syncytial virus (RSV) is a common cause of serious respiratory infections in hematopoietic stem-cell transplant (HSCT) recipients. We aimed to determine the frequency, risk factors, and outcome of RSV infection in allo-HSCT recipients.
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A novel haplo-identical adoptive CTL therapy as a treatment for EBV-associated lymphoma after stem cell transplantation.
Cancer Immunol. Immunother.
PUBLISHED: 09-22-2009
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Epstein-Barr virus (EBV)-related malignancies such as post-transplant lymphoproliferative disease (PTLD) are severe complications after allogeneic stem cell transplantation and solid-organ transplantation. In immunosuppressed transplant recipients, the activity of EBV-specific CTLs are often decreased or absent which leads to an increased risk of developing PTLD. If primary treatment modalities of PTLD fail, the most efficient way of treating the malignancy is adopting EBV-specific CTLs from the donor or, more recently, third-party donors. However, both are time consuming and expensive and often it is too late to administer cells to the patient. We have for the first time, using a rapid isolation protocol of EBV-specific T cells, treated and cured a patient suffering from PTLD with multiple-associated tissue lesions, using her haplo-identical mother as a donor. This treatment approach paves way for a new possibility to within-days treat patients with life-threatening EBV-associated malignancies.
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Stable mixed donor-donor chimerism after double cord blood transplantation.
Int. J. Hematol.
PUBLISHED: 04-14-2009
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Double cord blood transplantation (DCBT) has been used increasingly and has proven to be both safe and efficacious. In chimerism analysis, previous studies have indicated single unit predominance early after DCBT. In the present study, we evaluated the chimeric pattern in T-, B- and myeloid cells using PCR-based chimerism analysis in seven patients after DCBT: five patients had acute leukemia and two had lymphoma. Five patients received myeloablative conditioning and two patients were given reduced intensity conditioning. All patients received anti-thymocyte globulin (ATG) before DCBT. Three of the six evaluable patients showed donor-donor mixed chimerism in all cell lineages at 90 days after DCBT. Interestingly, two patients in long-term follow-up showed mixed donor chimerism in all cell lineages at 25 and 35 months after DCBT, respectively. Both patients are doing clinically well. Neither of the two developed GVHD after DCBT. In conclusion, in this study donor-donor mixed chimerism was common after high dose ATG and DCBT. Further studies are warranted concerning the immunological consequences of the phenomenon of donor-donor mixed chimerism after DCBT.
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Increased frequency and responsiveness of PSA-specific T cells after allogeneic hematopoetic stem-cell transplantation.
Transplantation
PUBLISHED: 03-25-2009
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Therapies for localized prostate cancer include curative surgery and radiotherapy while treatment of metastatic disease is often inefficient. Graft-versus-tumor effects of allogeneic stem-cell transplantation (ASCT) have been described for several types of solid tumors but have not been reported for prostate cancer. We, therefore, investigated the potential of ASCT as treatment for noncurable prostate cancer.
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Many days at home during neutropenia after allogeneic hematopoietic stem cell transplantation correlates with low incidence of acute graft-versus-host disease.
Biol. Blood Marrow Transplant.
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Patients are isolated in the hospital during the neutropenic phase after allogeneic hematopoietic stem cell transplantation. We challenged this by allowing patients to be treated at home. A nurse from the unit visited and checked the patient. One hundred forty-six patients treated at home were compared with matched hospital control subjects. Oral intake was intensified from September 2006 and improved (P = .002). We compared 4 groups: home care and control subjects before and after September 2006. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV was 15% in the "old" home care group, which was significantly lower than that of 32% to 44% in the other groups (P < .03). Transplantation-related mortality, chronic GVHD, and relapse were similar in the groups. The "new" home care patients spent fewer days at home (P = .002). In multivariate analysis, GVHD of grades 0 to I was associated with home care (hazard ratio [HR], 2.46; P = .02) and with days spent at home (HR, .92; P = .005) but not with oral nutrition (HR, .98; P = .13). Five-year survival was 61% in the home care group as compared with 49% in the control subjects (P = .07). Home care is safe. Home care and many days spent at home were correlated with a low risk of acute GVHD.
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Factors with an impact on chimerism development and long-term survival after umbilical cord blood transplantation.
Transplantation
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Umbilical cord blood transplantation (UCBT) is increasingly used and produces similar results to matched unrelated donor transplantation.
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Major surgery in a neutropenic patient undergoing allogeneic stem cell transplantation for high risk myelofibrosis.
Int. J. Hematol.
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Certain homeostatic functions are particularly important to the success of extensive surgery. For example metabolic homeostasis, inflammation and tissue repair, coagulation and immune defense against infection are all of great importance. In patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT), the ability to mount adequate inflammatory responses is severely impaired. Thrombocytopenia is common making coagulation inadequate for any kind of invasive procedure, let alone extensive surgery. For this reason, abdominal surgery in neutropenic patients is associated with very high mortality rates of between 50 and 70 % [1]. Here, we describe a patient with high-risk myelofibrosis who required extensive abdominal surgery during the aplastic phase only 7 days after ASCT due to severe abdominal hemorrhage. This patients successful recovery shows that extensive surgery is possible even during the aplastic phase after ASCT. Interestingly, we also found that radical splenectomy 7 days after stem cell transplantation did not lead to any significant loss of infused stem cells.
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Rapid salvage treatment with virus-specific T cells for therapy-resistant disease.
Clin. Infect. Dis.
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Viral infections are major complications after allogeneic hematopoietic stem cell transplantation (HSCT). During posttransplant immunosuppression the regular T-cell control is compromised. Even if treatment strategies against infections caused by herpes viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus have improved, the mortality rate is still considerable. If primary antiviral therapy fails or cannot be tolerated, adoptive therapy with virus-specific cytotoxic T cells (CTL) can be utilized.
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Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation.
Eur. J. Haematol.
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We performed a retrospective cohort study to find out whether the use of reduced-intensity conditioning (RIC) might reduce the risk of early death from pneumonia. Pneumonia-associated deaths were evaluated in 691 hematopoietic stem cell transplantation (HSCT) patients. The majority had a hematological malignancy (n = 504) and an HLA-matched donor (n = 584). RIC was given to 336 patients and myeloablative conditioning (MAC) to 355. Data concerning radiology, culture and autopsy results were evaluated together with risk factors for death related to pneumonia within or after 100 d after HSCT (early and overall pneumonia). In 60 patients, pneumonia contributed to death (early n = 17). The cumulative incidence of early pneumonia-related death was 2.8% and 2.1% in MAC and RIC patients, respectively. The cumulative incidence of overall pneumonia-related death was 8.2% and 10.5%, respectively. In 40 patients, (67%) an etiology could be established, with 19 patients having proven or probable mold infection. In the multivariate analyses, acute graft-versus-host disease (GVHD) grades II-IV, cytomegalovirus (CMV) infection and having received mesenchymal stromal cells (MSCs) were factors associated with overall pneumonia-related death. Bacteremia and a previous HSCT were associated with early pneumonia-related death. RIC did not reduce the incidence of early death associated with pneumonia. Acute GVHD II-IV, CMV infection and MSC treatment were factors associated with pneumonia-related death. Mold infection was the most common contributor to pneumonia-related death in HSCT patients.
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Effects of different serum-levels of ATG after unrelated donor umbilical cord blood transplantation.
Transpl. Immunol.
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We determined total rabbit-IgG (r-ATG) levels in serum samples before (day 0) and after (day 11 and day 25) unrelated donor umbilical cord blood transplantation (UCBT). Most patients (27/41) suffered from a haematological malignancy. There were 25 children and 16 adults. All patients received rabbit anti-thymocyte globulin (ATG) at a total dose of 6 or 8mg/kg as part of the conditioning. No correlation between the dose of ATG and serum r-ATG levels post UCBT was found. The cumulative incidence of acute GVHD grades III-IV in patients given the 6 and 8mg/kg ATG dose was 15% and 13% (ns), respectively. Patients with r-ATG?40?g/mL 11days after UCBT (n=19) had a higher incidence of grades III-IV acute GVHD (32% vs. 0%, p<0.01), higher TRM (69% vs. 7%, p=0.005), less relapse (17% vs. 82%, p<0.01) but similar relapse-free survival (RFS) (10% vs. 18%, p=0.4) compared to those with r-ATG>40?g/mL (n=17). Low serum-levels of r-ATG early after transplantation seem to be a strong predictor for acute GVHD grades III-IV, TRM and a low incidence of relapse in patients treated with thymoglobulin before unrelated donor UCBT.
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Update on viral infections in lung transplantation.
Curr Opin Pulm Med
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Lung transplantation is an established therapeutic option for patients with severe respiratory insufficiency. Graft dysfunction or rejection depends on the orchestrated prevention of infection(s) and the level of immune suppression. More recent reports underlined the role and pathogenicity of cytomegalovirus (CMV) infection in lung transplant recipients and the double-edged sword of maintaining antiviral immune responses versus guided immune suppression to avoid graft rejection. We present data concerning the nature of the cellular response to Epstein-Barr virus (EBV) and CMV, the subsequent use of cellular therapy in antiviral treatment modalities and discuss the role of H1N1 infection and other viral infections in lung transplantation recipients.
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Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation.
Clin. Immunol.
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We have previously successfully expanded functional T-cells in vitro from cord blood grafts used for clinical transplantation, with the aim of creating donor lymphocyte infusions to treat e.g. malignant relapse. Here we show that the T-cell expansion in addition might work as a prognostic tool for complications after transplantation. We used multi-color flow cytometry to correlate in vitro phenotypical and functional data from 33 expansions to clinical outcome post-transplantation. Higher levels of CD69+ activated T-cells in the expansion were associated with prolonged survival of the patient. In addition, we found a correlation between T-cell expansions containing relatively high levels of effector memory T-cells and graft vs. host disease and relapse. Our data suggest that expansions of cord blood T-cells from the graft might not only be used as donor lymphocyte infusions, but also as in vitro indicators that could give essential information on how to manage cord blood transplanted patients.
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