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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle-cell disease is a hereditary haemoglobinopathy caused by a mutation in the beta-globin gene. The disease is characterised by recurrent vaso-occlusive crises resulting in severe organ damage and a sharply reduced life expectancy. The formation of haemoglobin-S polymers in hypoxic conditions plays a pivotal role in sickle-cell disease and produces the characteristic phenotype of sickle-shaped erythrocytes that promote vasoocclusion. Endothelial cell activation, enhanced erythrocyte and leukocyte adhesion, vasoconstriction and coagulation activation play an important role in vaso-occlusive crises. Treatment of pain and hydration remain the main interventions in the management ofvaso-occlusive crises. Hydroxyurea has been shown to prevent vaso-occlusive crises by increasing the amount of foetal haemoglobin. Allogeneic stem-cell transplantation is the only curative therapy. However, transplantation-related mortality, graft-versus-host disease and the limited availability of HLA-identical donors restrict this therapeutic option.
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PMID:[Pathophysiology and treatment of sickle-cell disease]. 1653 53

Increased rates of graft rejection after bone marrow transplantation (BMT) are observed in patients whose illnesses--such as sickle cell disease, thalassemia, and aplastic anemia--necessitate chronic transfusion before BMT. Because BM transplants in these patients are routinely HLA matched, any immunization responsible for increased rejection is likely against minor histocompatibility antigens (mHAs). It has been assumed that contaminating leukocytes in red blood cell (RBC) units are the main sources of immunization to mHAs. However, in this report, we demonstrate that antigens on donor RBCs are presented in the major histocompatibility complex (MHC) class I pathway of recipient antigen-presenting cells, resulting in activation and expansion of recipient CD8+ T cells specific for donor mHAs. Given that human hematopoietic progenitor cells express many of the known mHAs, this observation provides a mechanism by which chronic transfusion of even stringently leukoreduced RBCs may result in sufficient mHA immunization to increase the frequency of BMT rejection.
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PMID:Immunization to minor histocompatibility antigens on transfused RBCs through crosspriming into recipient MHC class I pathways. 1612 13

Haemoglobin disorders are among the most frequent indications for preimplantation genetic diagnosis (PGD), introduced as an important option to couples at risk for producing offspring with thalassaemia and sickle cell disease. Previous experience mainly included PGD for beta-thalassaemia, while PGD for alpha-thalassaemia resulting in an unaffected pregnancy has not been reported. This study presents the results of the world's largest experience of 197 PGD cycles for haemoglobin disorders, which includes PGD for alpha-thalassaemia, resulting in 53 clinical pregnancies and birth of 45 healthy children, with five still ongoing. Fifty-four of these cycles were performed in combination with HLA typing, allowing the birth of thalassaemia-free children who were also HLA identical to the affected sibling, with successful stem cell transplantation in one case. As an increasing proportion of patients requesting PGD with HLA typing are of advanced reproductive age, aneuploidy testing was performed simultaneously with PGD. The results show that PGD has now become a practical approach for prevention of haemoglobin disorders, and is gradually being used also for improving access to HLA compatible stem cell transplantation for this group of diseases.
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PMID:Preimplantation diagnosis and HLA typing for haemoglobin disorders. 1617 79

HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) has a strong track record of efficacy and there is growing appreciation that its benefits exceed its risks in selected individuals. In contrast, the clinical utility of replacement gene therapy for sickle cell disease remains unproven. Its challenge is to ensure viral transduction into hematopoietic stem cells (HSCs) and to generate safe, stable, erythroid-specific replacement gene expression at a level that is sufficient to have a clinical effect. The clinical necessity for fulfilling all these criteria may make this genetic disorder among the most complex to treat successfully by gene therapy. But the experience of HCT for SCD has proven that eliminating the beta(S)-globin gene is curative when the transfer is stable. Thus replacement gene therapy for sickle cell disease remains a subject of intense interest and investigation.
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PMID:Stem cell therapy for sickle cell disease: transplantation and gene therapy. 1630 61

This study examined the theoretical availability of compatible unrelated umbilical cord blood (UCB) units for hematopoietic stem cell transplantation (HSCT) of children with sickle cell disease (SCD), matched for DRB1 at high resolution. UCB units registered via Bone Marrow Donors Worldwide were matched with patients who had been previously typed for possible HSCT. Suitable matching was determined after typing at antigen level at A and B loci and allele-level typing at DRB1. Forty patients met criteria for analysis. All matched at four of six loci with at least two UCB units, and 50% (n = 20) matched at five of six loci with at least one unit. In patients matched at four loci or more, significantly more units per patient (median 19 vs. 2 units; P = 0.03) at higher cell dose (median 205 vs. 113 best nucleated cell dose per unit; P < 0.01) were identified compared with patients matched at five loci or more. Hypothetically, at a dose of at least 5 x 10 nucleated cells/kg, 54% of patients weighing 40 kg would match with units at four or more of six loci and 5% at five or more of six loci. This study suggests that cord blood units matching at four or more of six HLA loci at acceptable cell doses can be identified for a majority of children with SCD weighing 40 kg or less. Availability of units matched at five or more of six HLA loci was more limited. Defining procedure-related risks and benefits remains a challenge.
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PMID:Identification of unrelated cord blood units for hematopoietic stem cell transplantation in children with sickle cell disease. 1639 89

Hematopoietic stem cell transplantation is the sole curative therapy for sickle cell anemia (SCA). This treatment is restricted to severe forms of disease. Lack of HLA-identical sibling donor is the major limiting factor for delivering this therapy. Conditioning regimen should be myeloablative. Post transplantation immunosuppressive medication is necessary for both graft tolerance and graft-versus-host disease (GvHD) control. For the majority of patients, bone marrow is source of stem cells. Alternative sources including related cord blood stem cells are under evaluation and promising. Outcome for 250 grafted patients worldwide is excellent. More than 85 % survive free of SCA and have a good quality of life although GvHD remains the main complication.
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PMID:[Hematopoietic stem cell transplantation for severe sickle cell disease]. 1645 29

The thalassemias, sickle cell disease, and other hemoglobinopathies represent a major group of inherited disorders of hemoglobin synthesis. The abnormal hemoglobins were reviewed in the July 2006 issue of Baylor University Medical Center Proceedings. Because of immigration patterns and population flow, these disorders are becoming increasingly more prevalent in the USA. In this article, the clinical aspects of the more common thalassemia syndromes are reviewed. For most symptomatic patients with thalassemia, there is no definite cure; only supportive management of the anemia is possible. A very limited number of patients with thalassemia may be cured by bone marrow transplantation from HLA-identical donors. Other tentative approaches to management include stimulation of fetal hemoglobin synthesis and attempts at somatic cell gene therapy. Prevention of disease transmission by carrier screening programs along with prenatal diagnosis remain of paramount importance in the reduction of these diseases worldwide.
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PMID:The thalassemias and related disorders. 1725 39

Anti-CD36 antibodies are known to cause a platelet refractory state. We describe a previously unreported case of a 16-year-old female sickle cell disease patient with anti-CD36 antibodies, detected on routine screen prior to hematopoietic stem cell transplantation (HSCT). CD36 platelet antigen typing was negative for both the patient and her HLA-identical donor sibling. Patient plasma was compatible with 48 of 49 apheresis platelets, which were untested and presumably positive for the CD36 antigen. The patient responded adequately to transfusion of crossmatch compatible platelets and successfully underwent HSCT. The presence of anti-CD36 antibodies does not exclude potential candidates from HSCT.
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PMID:CD36 immunization in a patient undergoing hematopoietic stem cell transplantation. 1733 Aug 34

The 10-year graft survival rates for first renal transplants performed during 1990-1994 and 1995-1999 and reported to the OPTN/UNOS Renal Transplant Registry increased from 57-58% for living donor transplants, from 42-46% for deceased donors aged 60 or under, and from 22-28% for donors over age 60 comparing the 2 intervals. These modest increases were accompanied by a 2% decline in 10-year patient survival for recipients of living and younger deceased donor grafts and a 1% improvement in patient survival for recipients of older donor kidneys. The 5-year graft and patient survival rates for transplants performed between 2000 and 2004 were 80% and 90% for living donor, 69% and 90% for standard criteria deceased donor and 55% and 82% for expanded criteria donor transplants, respectively. There was no significant improvement when compared to the 1995-1999 period for any of these groups and patient survival had declined by 1% among recipients of living or standard criteria deceased donors. recipients of living or standard criteria deceased donor kidneys had a 6-7% higher 5-year survival rate and longer graft half-lives than recipients of HLA mismatched kidneys. The number of local HLA-DR matched transplants (excluding zero-HLA-ABDR mismatched grafts) has been declining since 1998 and was affected by the activity of the local donation service area (presumably reflecting the size of the waiting list). There was a modest increase in the percentage of broadly sensitized recipients transplanted during 2002-2004 from 8-10% of standard deceased donor The median age for recipients of primary standard criteria deceased donor transplants increased from 43 during the period 1990-1994 to 51 during 2000-2004 and may explain the lack of improvement in long-term graft survival rates. When patients aged 19-35 were analyzed separately during the 3 periods, there was a 3-4% increase in actuarial or projected 10-year graft survival for recipients of living or younger deceased donor kidneys during each interval (p < 0.001). Changes to the kidney allocation algorithm that affect the role of HLA matching have not had a striking impact on the number or percentage of zero HLA-ABDR mismatched SCD transplants, which account for 16-17% of SCD transplants each year. The number and percentage of HLA-matched ECD transplants declined from 113 (12%) in 2001 to 63 (4%) in 2004. The 56% 5-year graft survival rate for recipients of HLA-matched ECD kidneys was not significantly better than that for HLA-mismatched grafts, whereas HLA-matched and from 2-4% of living donor kidney recipients that was temporally associated with improved technologies for detecting anti-HLA antibodies. The presence of panel reactive antibodies had almost no effect on 5-year graft survival among retransplanted patients. The number of transplants between spouses leveled off in 2001 at about 700 transplants each year. The number of non-spouse unrelated living donor transplants has increased 10-fold over the past 10 years to 1,341 in 2004 and does not appear to be slowing.
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PMID:The OPTN/UNOS Renal Transplant Registry. 1742 21

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD); nevertheless, its use has been limited by the risk of transplantation-related mortality (TRM). Between November 1988 and December 2004, 87 consecutive patients with severe SCD ranging from 2 to 22 years of age received transplants in France. Cerebral vasculopathy was the principal indication for transplantation (55 patients). All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (CR). The only change in the CR during the study period was the introduction of antithymocyte globulin (ATG) in March 1992. The rejection rate was 22.6% before the use of ATG but 3% thereafter. With a median follow-up of 6 years (range, 2.0 to 17.9 years), the overall and event-free survival (EFS) rates were 93.1% and 86.1%, respectively. Graft versus host disease (GVHD) was the main cause of TRM. Importantly, cord blood transplant recipients did not develop GVHD. No new ischemic lesions were detected after engraftment, and cerebral velocities were significantly reduced. The outcome improved significantly with time: the EFS rate among the 44 patients receiving transplants after January 2000 was 95.3%. These results indicate that HLA-identical sibling HSCT after myeloablative conditioning with ATG should be considered as a standard of care for SCD children who are at high risk for stroke.
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PMID:Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. 1822 76


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