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Haematopoietic Stem Cell Transplantation (haematopoietic + stem_cell_transplantation)
Kinds of Haematopoietic Stem Cell Transplantation Selected AbstractsCD34+ stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficienciesBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2006Claire Booth Summary Haematopoietic stem cell transplantation can be limited by ineffective haematopoiesis and poor immune recovery. A CD34+ cell infusion without conditioning has the potential to improve stem cell function with limited toxicity. Eighteen patients with congenital immunodeficiencies received CD34+ boosts for various defects. When given <1 year after the original graft, six of seven cytopenic patients achieved transfusion independence. A second cohort (n = 11) received boosts >1 year after the original graft; only minimal changes in immune function or chimaerism were noted. Unconditioned stem cell boosts have limited toxicity but should be given early after the original graft to be effective. [source] Haematopoietic stem cell transplantation for Shwachman,Diamond disease: a study from the European Group for blood and marrow transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2005Simone Cesaro Summary This report assessed the results of allogeneic stem cell transplantation (allo-SCT) in 26 patients with Shwachman,Diamond disease (SDS) and severe bone marrow abnormalities. The conditioning regimen was based on busulphan (54%), total body irradiation (23%), fludarabine (15%) or other chemotherapy combinations (8%). Standard prevention of graft versus host disease (GVHD) with ciclosporin ± methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T-cell depletion was used in 17 and four patients respectively. Neutrophil and platelet engraftment were achieved in 21 (81%) and 17 (65%) of 26 patients after a median time of 18 days and 29 days respectively. The incidence of grade III and IV acute GVHD was 24% and of chronic GVHD 29%. Nine patients died after a median time of 70 d, post-SCT. After a median follow-up of 1·1 years, the transplant-related mortality was 35·5% (95% CI 17,54) whilst the overall survival was 64·5% (95% CI 45·7,83·2). Allo-SCT was found to be successful in more than half of SDS patients with severe bone marrow dysfunction. Further improvements would be anticipated by a better definition of the optimum time in the course of disease to transplant and by the adoption of less toxic conditioning regimens. [source] Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005AnnaCarin Horne Summary Haemophagocytic lymphohistiocytosis (HLH) poses major therapeutic challenges, and the primary inherited form, familial haemophagocytic lymphohistiocytosis (FHL), is usually fatal. We evaluated, including Cox regression analysis, survival in 86 children (29 familial) that received HLH-94-therapy (etoposide, dexamethasone, ciclosporin) followed by allogeneic stem cell transplantation (SCT) between 1995 and 2000. The overall estimated 3-year-survival post-SCT was 64% [confidence interval (CI) = ±10%] (n = 86); 71 ± 18% in those patients with a matched related donor (MRD, n = 24), 70 ± 16% with a matched unrelated donor (MUD, n = 33), 50 ± 24% with a family haploidentical donor (haploidentical, n = 16), and 54 ± 27% with a mismatched unrelated donor (MMUD, n = 13). After adjustment for potential confounding factors, estimated odds ratios (OR) for mortality were 1·93 (CI =0·61,6·19) for MUD, 3·31 (1·02,10·76) for haploidentical, and 3·01 (0·91,9·97) for MMUD, compared with MRD. In children with active disease after 2-months of therapy (n = 43) the OR was 2·75 (1·26,5·99), compared with inactive disease (n = 43). In children with active disease at SCT (n = 37), the OR was 1·80 (0·80,4·06) compared with inactive disease (n = 49), after adjustment for disease activity at 2-months. Mortality was predominantly transplant-related. Most HLH patients survived SCT using MRD or MUD, and survival with partially mismatched donors was also acceptable. Patients that responded well to initial pretransplant-induction therapy fared best, but some persisting HLH activity should not automatically preclude performing SCT. [source] Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directionsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005A. Tyndall Summary Around 700 patients have received an autologous haematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The majority of these have been within the context of phase I/II clinical trials and following international guidelines proposed 7 years ago. In general, a positive benefit/risk ratio has led to phase III prospective randomized controlled trials in multiple sclerosis (MS), systemic sclerosis (SSc) and rheumatoid arthritis (RA) in Europe. In the US, similar trials are being planned for SSc, MS and systemic lupus erythematosus (SLE). Transplant related mortality (TRM) has fallen in all disease subgroups since the inception due to more appropriate patient selection, and so far a clear advantage of the more intense myeloablative regimens in terms of remission induction and relapse rate has not emerged. Although each AD has a different profile, over a third of patients have sustained a durable remission, often with no further need for immunosuppressive drugs. In those who relapsed, many responded to agents which pre transplant had been ineffective. The study of immune reconstitution and gene expression pre and post HSCT is being undertaken to further understand the mechanism of autoimmunity. [source] Health psychology and distress after haematopoietic stem cell transplantationEUROPEAN JOURNAL OF CANCER CARE, Issue 1 2009V. DeMARINIS phd The purpose of this study of 23 adult haematopoietic stem cell transplantation (HSCT) recipients is to compare the presence of post-transplantation depression disorders by gender and to compare the outcomes among those with and without depressive disorders using a health psychology focus. This cross-sectional pilot study of mid-term survivors took place in hospital outpatient clinic. Main outcome measures are depression disorders, health status (Short Form-12) and health anxiety. Female survivors had a higher rate of depression disorders, but those with treated depressive disorders were similar to those without depression on health-related quality of life and health anxiety. Neither patient age nor time since HSCT was associated with depressive disorders. A health psychology approach may enhance management of HSCT survivorship. [source] Health-related quality of life, symptom distress and sense of coherence in adult survivors of allogeneic stem-cell transplantationEUROPEAN JOURNAL OF CANCER CARE, Issue 2 2001L. Edman This is the first Swedish study to evaluate the health-related quality of life and sense of coherence in adult survivors of allogeneic, haematopoietic stem cell transplantation (HSCT). Twenty-five recipients completed three questionnaires 2,4 years after the transplantation. The questionnaires used were the Sickness Impact Profile (SIP), the Symptom Frequency Intensity and Distress (SFID-BMT) scale and the Sense of Coherence (SOC) scale measuring subjective functional status, symptom distress and coping ability. Impairments in functional status were found, as compared with a population norm. The most common impairments were found in the areas of social interaction and sleep and rest. Eye problems, dry mouth, cough, sexual problems, tiredness, anxiety and changes of taste were symptoms reported by more than half of the patients. Despite impaired functioning and a high incidence of symptoms, the general health was described as quite good or excellent by 80% (n = 20) of the patients. The majority (20/22) had also been able to return to work or to attend school. No difference in the sense of coherence was seen, as compared with the population norm. Functional impairments were significantly correlated to a lower degree of sense of coherence. [source] Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamideEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2002H.W. Auner Abstract:Objectives : Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). Patients and methods : We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. Results: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrythmias were not observed. Conclusions : These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy. [source] Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations,HUMAN MUTATION, Issue 1 2010Alessandra Pangrazio Abstract The "Osteopetroses" are genetic diseases whose clinical picture is caused by a defect in bone resorption by osteoclasts. Three main forms can be distinguished on the basis of severity, age of onset and means of inheritance: the dominant benign, the intermediate and the recessive severe form. While several genes have been involved in the pathogenesis of the different types of osteopetroses, the CLCN7 gene has drawn the attention of many researchers, as mutations within this gene are associated with very different phenotypes. We report here the characterization of 25 unpublished patients which has resulted in the identification of 20 novel mutations, including 11 missense mutations, 6 causing premature termination, 1 small deletion and 2 putative splice site defects. Careful analysis of clinical and molecular data led us to several conclusions. First, intermediate osteopetrosis is not homogeneous, since it can comprise both severe dominant forms with an early onset and recessive ones without central nervous system involvement. Second, the appropriateness of haematopoietic stem cell transplantation in CLCN7-dependent ARO patients has to be carefully evaluated and exhaustive CNS examination is strongly suggested, as transplantation can almost completely cure the disease in situations where no primary neurological symptoms are present. Finally, the analysis of this largest cohort of CLCN7-dependent ARO patients together with some ADO II families allowed us to draw preliminary genotype-phenotype correlations suggesting that haploinsufficiency is not the mechanism causing ADO II. The availability of biochemical assays to characterize ClC-7 function will help to confirm this hypothesis. © 2009 Wiley-Liss, Inc. [source] Association of IL-6 gene polymorphism with the outcome of allogeneic haematopoietic stem cell transplantation in Czech patientsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4-5 2008Z. Ambruzova Summary Interleukin-6 (IL-6) is an important pro-inflammatory mediator implicated in immune-mediated complications of allogeneic haematopoietic stem cell transplantation (aHSCT). In accord with previous reports, this preliminary study on 56 donor,recipient pairs revealed IL-6-174 single nucleotide polymorphisms as a risk factor for the development of acute graft-versus-host disease and decreased survival after aHSCT. [source] Distribution of killer cell immunoglobulin-like receptor genes in PolesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4-5 2008E. Majorczyk Summary Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leucocyte antigen (HLA) molecules on the surface of target cells. Humans differ by the presence or absence of some KIR genes on their chromosomes. As KIRs are important for the outcome of tissue transplantation (particularly for haematopoietic stem cell transplantation) and possibly for pregnancy and autoimmune diseases, knowledge of the KIR gene distribution in a given human population is of practical value. Therefore, we tested 363 healthy individuals from Western Poland for the presence or absence of KIR genes. Results are compared with those published for other human populations. KIR gene frequencies in Poles are close to these in other Caucasoids but different from those in Asian and African populations, and particularly distant from those in Australian Aborigines. [source] Current practice of antifungal prophylaxis and treatment in immunocompromised children and adults with malignancies: a single centre approachMYCOSES, Issue 2 2009Thomas Lehrnbecher Summary Although various guidelines on antifungal prophylaxis and treatment have been published, the practical approach in the individual clinical setting might considerably differ because of special local circumstances. In addition, there are major differences between paediatric and adult patients regarding antifungal strategies and the use of antifungal compounds. We here present the antifungal approach in the Departments of Hematology and Oncology of the University Hospital of Frankfurt, where per year approximately 350 children and adults are diagnosed with cancer and an additional 100 patients undergo haematopoietic stem cell transplantation. The differences in the approach between the paediatric and adult setting are highlighted. [source] Many faces of graft- versus -host diseaseAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2010Pablo F Peñas ABSTRACT Allogeneic haematopoietic stem cell transplantation is increasingly used in the treatment of malignant and non-malignant disorders. Despite ongoing advances in the field, morbidity and mortality related to graft- versus -host disease remains a major barrier to its application. Graft- versus -host disease is a difficult-to-diagnose disease. Dermatologists are involved due to its diverse cutaneous expression. In order to appropriately diagnose, classify and treat this complex disease, knowledge of its expanding cutaneous expression is required. This review provides a synopsis of the clinical manifestations of acute, lichenoid and sclerodermatous phases of graft- versus -host disease with a look at the current evidence surrounding its differential diagnosis. [source] A case of tongue carcinoma associated with chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantationAUSTRALIAN DENTAL JOURNAL, Issue 2 2010K Noguchi Abstract Graft-versus-host disease (GVHD) can occur at various sites, including the oral mucosa, where it is associated with a high risk of head and neck cancer. We report the case of a 46-year-old woman with tongue cancer that developed following Hodgkin's lymphoma and chronic GVHD, and we discuss the possible causes of cancer development. [source] Nailfold capillary abnormalities are prevalent in sclerodermoid graft-versus-host disease and readily detected with dermatoscopyBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2010B.N. Akay Summary Background, Well-recognized videocapillaroscopic patterns have been described in systemic sclerosis (SS). However, no studies have described the capillary abnormalities of sclerodermoid chronic graft-versus-host disease (Scl GVHD) developed after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Objectives, The aims of this study were to find the characteristics of nailfold capillary changes in Scl GVHD after allo-HSCT. Patients and methods, Eighteen patients affected by Scl GVHD and a control group of 15 patients with lichenoid GVHD were evaluated. Duration and type of sclerodermoid GVHD, Raynaud phenomenon (RP), dysphagia, joint contractures, antinuclear antibodies (ANA), anti-Scl-70 and anticentromere (ACA) antibodies were investigated parameters. A nailfold capillary examination using a standard dermatoscope was performed on all fingers of each subject. Results, Twelve patients were male and six were female with a mean age of 37 ± 11·6 years. Joint retractions and dysphagia developed in 27·8% and 38·9% of the patients, respectively. Three (16·7%) patients had RP. Autoimmune markers like anti-Scl-70 and ACA were negative in all. Capillaroscopy was abnormal in 15 patients with Scl GVHD. A regular disposition of the capillary loops along with avascular whitish linear areas at the level of the last row, neovascularization with reticular pattern, capillary disorganization, haemorrhages, enlarged capillaries and avascular areas were the main features. No capillary abnormalities were observed in patients with lichenoid GVHD. There was no statistically significant correlation between ANA positivity, RP, joint retractions, dysphagia, extensiveness of Scl GVHD, duration of sclerodermoid lesions and nailfold capillaroscopy analysis. Conclusions, This study shows the identification of distinct nailfold capillaroscopy patterns in patients with Scl GVHD but it does not confer special risk for any other specific clinical symptoms of the disease. [source] correspondence: Splenectomy after allogeneic haematopoietic stem cell transplantation in patients with primary myelofibrosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2010Marie Robin First page of article [source] Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord bloodBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2009Angela R. Smith Summary Umbilical cord blood has rapidly become a valuable alternative stem cell source for allogeneic haematopoietic stem cell transplantation. Extensive research over the last 20 years has established the safety and efficacy of umbilical cord blood transplantation in both children and adults with a variety of malignant and non-malignant diseases. This research has clearly shown that this stem cell source has several unique characteristics resulting in distinct advantages and disadvantages when compared to transplantation with unrelated bone marrow or peripheral blood stem cells. This article reviews the most recent literature comparing the outcomes after umbilical cord blood transplantation with other alternative stem cell sources. [source] Impact of allogeneic haematopoietic stem cell transplantation in the outcome of Ph+ acute lymphoblastic leukaemia treated with an imatinib-containing regimenBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Luciano J. Costa No abstract is available for this article. [source] Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapyBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2008Masamitsu Yanada Summary The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0·800 and P = 0·964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2·9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect. [source] Influence of bone marrow nucleated red blood cell dose on outcome after allogeneic haematopoietic stem cell transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Marie Robin No abstract is available for this article. [source] Association of autoimmune disease-related gene polymorphisms with chronic graft-versus-host diseaseBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007Masako Shimada Summary Chronic graft-versus-host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease-related genes might be candidate chronic GVHD-related genes. Recent large-scale cohort studies showed that Fc receptor-like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen-matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis-specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3 -169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0·0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD. [source] Systematic review of high dose chemotherapy and autologous haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: what is the published evidence?BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2007Mohamed A. Kharfan-Dabaja Summary Despite improved responses, chronic lymphocytic leukaemia (CLL) remains incurable with conventional chemotherapy. Patients with poor-risk factors or who fail conventional chemoimmunotherapy are offered autografts, preferably after achieving remission. This report presents the totality of evidence through a systematic review that assessed the efficacy of autografts in CLL. A search of MEDLINE databases from 1966,2006 and hand-search of references identified 82 prospective-randomized, non-randomized comparisons or single-arm trials, of which only nine met our inclusion criteria: two trials were funded by public/government, one by private foundations, one jointly by private/public, and was unclear in five. No randomized controlled trials comparing autografts versus conventional chemotherapy (or chemoimmunotherapy) were found. Six studies were single-arm and three were non-randomized with a control-arm (autologous versus allogeneic). Overall, 361 patients were enrolled, but only 292 were transplanted. Transplant-related mortality ranged from 0% to 9%. Complete responses ranged from 74% to 100% and molecular responses ranged from 57% to 88%. Overall survival ranged from 68% at 3 years to 58% at 6 years. It is uncertain whether autograft is superior to conventional therapy. The high incidence of myelodysplastic syndrome (9,12%) is particularly concerning in CLL, where median survival is 9 years. [source] Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: report from the Research on Adverse Drug Events and Reports (RADAR) projectBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Charles L. Bennett Summary Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) and granulocyte colony-stimulating factor (G-CSF) promote haematopoietic progenitor cell maturation. We reviewed the findings for healthy volunteers/donors who developed haematological malignancies following PEG-rHuMGDF or G-CSF administration. Information was reviewed for three of 538 volunteers who received PEG-rHuMGDF in clinical trials and two of 200 donors who underwent G-CSF mobilised stem cell harvesting procedures for sibling stem cell transplants. Mantle cell, diffuse large B-cell lymphoma and chronic lymphocytic leukaemia were diagnosed 1,5 years after PEG-rHuMGDF exposure among three volunteers. For one patient, thrombocytopenia due to autoantibodies to PEG-rHuMGDF developed shortly after PEG-rHuMGDF administration and persisted until chemotherapy was administered. All three achieved complete remission, although one patient relapsed. Acute myeloid leukaemia was diagnosed 4 and 5 years after G-CSF mobilisation in two donors who underwent peripheral blood stem cell donation for sibling allogeneic haematopoietic stem cell transplantation. Following intensive chemotherapy, one died from acute leukaemia and the second is in complete remission. Controversy exists over the appropriateness of administering haematopoietic growth factors to healthy individuals. While a causal relationship with haematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive haematopoietic growth factors is needed. [source] CD34+ stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficienciesBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2006Claire Booth Summary Haematopoietic stem cell transplantation can be limited by ineffective haematopoiesis and poor immune recovery. A CD34+ cell infusion without conditioning has the potential to improve stem cell function with limited toxicity. Eighteen patients with congenital immunodeficiencies received CD34+ boosts for various defects. When given <1 year after the original graft, six of seven cytopenic patients achieved transfusion independence. A second cohort (n = 11) received boosts >1 year after the original graft; only minimal changes in immune function or chimaerism were noted. Unconditioned stem cell boosts have limited toxicity but should be given early after the original graft to be effective. [source] Evaluation of cytomegalovirus-specific T-cell reconstitution in patients after various allogeneic haematopoietic stem cell transplantation using interferon- , -enzyme-linked immunospot and human leucocyte antigen tetramer assays with an immunodominant T-cell epitopeBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2005Mutsuko Ohnishi Summary Cytomegalovirus (CMV) infection is a major complication for patients who received allogeneic haematopoietic stem cell transplantation (HSCT). Accurate monitoring of CMV-specific T-cell reconstitution is required for appropriate decision on treatment, such as anti-viral drugs, which have adverse effects. Although human leucocyte antigen (HLA) tetramer and interferon- , -enzyme-linked immunospot (IFN- , -ELISPOT) assays have been used to measure CMV-specific T cells, detailed comparison of these assays and kinetics of anti-CMV T-cell reconstitution between reduced-intensity transplantation (RIST) and conventional HSCT has not yet been performed. In this study, we performed prospective comparative monitoring of CMV-specific T cells using HLA tetramer and IFN- , -ELISPOT assays with a single immunodominant CMV495 peptide in 28 HLA-A*0201 and 9 HLA-A*0206 patients after various allogeneic HSCTs. The IFN- , -ELISPOT assay was more sensitive for evaluation of functional T cells than the HLA tetramer assay, and CMV-specific T cells were reconstituted earlier in patients who received RIST without anti-thymocyte globulin (ATG) than those receiving RIST with ATG or conventional HSCT. The threshold level for protection from CMV reactivation was estimated as over 1 × 106 cells/l peripheral blood with the IFN- , -ELISPOT assay. These results demonstrate that the IFN- , -ELISPOT assay with CMV495 provides more accurate evaluation on CMV immunity in HLA-A*0201 and -A*0206 patients, and may be useful for determining timing of various treatments. [source] Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992,2001BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Merete Stubkjaer Christensen Summary Despite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2,5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology-ALL92 protocol included 1652 patients ,15 years of age with precursor B- and T-cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment-related death (TRD) [relative risk (RR) = 2·2; 95% confidence interval (CI95%): 1·2,4·0, P < 0·01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4·5; CI95%: 2·0,10·2, P < 0·00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL. [source] A UGT2B17-positive donor is a risk factor for higher transplant-related mortality and lower survival after bone marrow transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2005Seitaro Terakura Summary We recently identified a human minor histocompatibility (H) antigen, encoded by UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17), whose immunogenicity results from differential expression in donor and recipient cells as a consequence of a homozygous deletion of the UGT2B17 gene. UGT2B17 is highly expressed in the liver and colon, which are major targets for graft- versus -host disease (GVHD). To assess the significance of homozygous UGT2B17 gene deletion in allogeneic haematopoietic stem cell transplantation (HSCT), we analysed DNA from 435 stem cell transplant recipients with a haematological malignancy and their human leucocyte antigen-identical unrelated bone marrow donors using sequence-specific primer polymerase chain reaction. Homozygous deletion of the UGT2B17 gene was observed in 85% of normal donors and in 82% of patients. The analysis showed no significant association between UGT2B17 mismatch in the GVHD direction and the incidence of acute GVHD, chronic GVHD, relapse, or survival. However, the use of a UGT2B17-positive donor was an independent risk factor for higher transplant-related mortality and lower survival after transplantation. UGT2B17 is a metabolic enzyme for hormones, drugs, and potentially toxic exogenous compounds and is expressed in subsets of haematopoietic cells. Thus, the enzyme function of UGT2B17 in donor cells may affect the outcome of allogeneic HSCT. [source] The impact of retroviral suicide gene transduction procedures on T cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Waseem Qasim Summary., Retroviral vectors encoding the herpes simplex thymidine kinase gene have been used to render T cells sensitive to the prodrug ganciclovir. Such genetically modified T cells have been used in clinical trials for their graft-versus-leukaemia effects following allogeneic haematopoietic stem cell transplantation. In the event of graft-versus-host disease (GVHD) the cells were susceptible to elimination through exposure to ganciclovir. We have investigated the impact of T-cell activation, required for successful retrovirus-mediated gene transfer, on T-cell receptor repertoire profile, subset distribution and antiviral potential. Using a combination of antibodies against CD3 and CD28, T cells were transduced at high efficiency when exposed to retrovirus between 48 and 72 h later. Lymphocytes had undergone up to seven cycles of cell division by the end of the procedure. Although the T-cell receptor V, repertoire was not altered after retroviral transduction, there were notable shifts in subset profiles with an increased proportion of CD45RO cells in transduced populations. T cells continued to proliferate for several days after transduction and were difficult to sustain under the extended culture conditions required to generate virus-specific T cells. These observations may explain the lower than expected levels of GVHD and poor antiviral immunity reported in recent trials. [source] Activating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemiasCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009A. Moretta Summary A number of experimental studies have shown that natural killer (NK) cells can eliminate cancer cells and the mechanisms involved in this effect have been uncovered during the last two decades. Clinical data from haploidentical haematopoietic stem cell transplantation (haplo-HSCT) revealed that NK cells were responsible for remarkably favourable effects in both adult and paediatric high-risk leukaemias. NK receptors specific for major histocompatibility complex (MHC) class I molecules, including killer immunoglobulin (Ig)-like receptors (KIR) and CD94/NKG2A, play a major role in the anti-leukaemia effect (mediating either inhibitory or activating signals). Haplo- HSCT requires a heavy conditioning regimen for the patient and the use of large numbers of T cell-depleted HSC to be grafted. After transplantation, natural killer cells develop from HSC shortly after engraftment and may include ,alloreactive' NK cells that kill leukaemic cells and prevent graft- versus -host disease (GvHD). Alloreactive NK cells are characterized by the expression of KIR that are not engaged by any of the human leucocyte antigen (HLA) class I alleles expressed by the patient. Their generation is dependent upon the existence of a KIR/HLA class I mismatch between donor and recipient. Novel important information on the function and specificity of different KIR has been obtained recently by the analysis of donor-derived alloreactive NK cells in a cohort of paediatric patients given haplo-HSCT to cure acute, high-risk leukaemias. [source] Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factorsBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2009Vanderson Rocha Summary The use of unrelated umbilical cord blood (UCB) as an alternative source of haematopoietic stem cells transplantation (HSCT) has been widely used for patients lacking a human leucocyte antigen (HLA) matched donor. One of the disadvantages of using UCB is the limited number of haematopoietic stem cells and, consequently, delayed engraftment and increased risk of early mortality. Many approaches have been investigated in the attempt to improve engraftment and survival. Among those, studies analysing prognostic factors related to patients, disease, donor and transplantation have been performed. Variable factors have been identified, such as factors related to donor choice (HLA, cell dose and others) and transplantation (conditioning and graft- versus -host disease prophylaxis regimens). This review will focus on the interactions between HLA, cell dose and other modifiable factors related to the UCB unit selection and transplantation that may improve outcomes after UCB transplantation. [source] | |||||||||||||||||||||||||