Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UCBT was performed in seven children with SCD and stroke (HLA match 4/6 n=5; 5/6 n=2). Four received myeloablative regimens (BU, CY, ATG plus FLU in one patient). One had primary graft failure, three had sustained engraftment, two with grade III-IV GVHD (one died, one developed chronic GVHD), one with stable mixed chimerism. Three patients treated with reduced-intensity regimens (FLU, BU or CY, ATG, TLI) failed to engraft; one engrafted after second UCBT (HU, TT, RXA, ALZ, TBI). Four patients (57%) developed viral infections. Engraftment, GVHD, and infection remain challenges.
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PMID:Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience. 1766 78

Currently, hematopoietic SCT (HCT) is the only intervention that can restore normal hematopoiesis to provide a 'cure' in sickle cell disease. Yet, this treatment modality is used sparsely-a total of less than 400 transplants are reported in the Center for International Blood and Marrow Transplant Research database despite 70,000 afflicted in the United States; 88% of transplants are from HLA-matched sibling donors and 84% are <16 years of age at transplant. Overall survival at 3 years is over 90% after HCT in the young but 62% in adult HCT recipients due to increased disease and transplant-related morbidity. The decision and timing of HCT is a dilemma for physicians and families due to the need to consider HCT before severe organ damage in a disease that is generally not fatal in children with adequate supportive care. From the transplant physician's perspective, however, advances in the ability to identify well-matched donors, supportive care and promising conditioning regimens with low toxicity and transplant complications support the development of new HCT trials for sickle cell disease as the risk/benefit ratio can be balanced better. With the recognition of new predictors of early mortality, the anticipation of extensive and expensive life-long medical support, and the poor quality of life despite medical care, the scales tip in favor of HCT. This is prime time for the development of careful unrelated donor HCT trials for sickle cell disease. Research efforts targeting HCT will need to be directed at seeking safe and effective transplant methods applicable to all patients who might derive benefit.
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PMID:Has stem cell transplantation come of age in the treatment of sickle cell disease? 1770 97

Severe bacterial infections are the major causes of morbidity and mortality in sickle cell anemia (SCA) but are poorly explained. The distribution of a bi-allelic polymorphism (Arg107Gly) of human leukocyte antigen-E (HLA-E) locus was investigated in 144 SCA patients, most of whom originated from from sub-Saharan Africa. Among them, 73 presented with at least one severe bacterial infection, whereas 71 did not. The HLA-E*0101/E*0101 genotype was more frequent among the group with infections than their counterparts (47% vs 21%; p corrected = 0.003). This genetic association is of relevance, given the emerging evidence for the involvement of HLA-E molecules in host response to pathogens.
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PMID:HLA-E*0101 allele in homozygous state favors severe bacterial infections in sickle cell anemia. 1796 74

End-organ damage is common in patients with sickle cell disease (SCD) thereby limiting the use of allogeneic stem cell transplantation (SCT). We report the outcome of 2 adult SCD patients, 1 with end-stage renal disease (ESRD), who underwent fludarabine-based nonmyeloablative SCT from HLA-identical matched siblings. To prevent fludarabine toxicity, the patient with ESRD underwent aggressive dialysis following adjusted fludarabine dosing. Pharmacokinetics of the fludarabine metabolite F-Ara-A was studied on the patient with ESRD and 2 additional patients with normal renal function. Both patients with SCD achieved full donor erythroid chimerism, have normal blood counts, and are on no immunosuppressive medications. With a 20% dose reduction followed by daily dialysis, we achieved fludarabine drug exposure that is nearly identical to that achieved in patients with normal renal function. We conclude that fludarabine-based nonmyeloablative allogeneic SCT for adult patients with SCD is feasible, even in the setting of ESRD.
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PMID:Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics. 1802 71

The life expectancy of patients with sickle cell disease has improved in the United States and Europe thanks to the use of penicillin prophylaxis, appropriate immunizations, neonatal screening, implementation of a quality transfusional policy, hydroxyurea therapy, detection and treatment of cerebral vasculopathy, recognition of situations that can benefit from allogenic marrow transplantation, and improvements in bone marrow transplantation techniques. The cost of almost all these techniques is far beyond the means of health care systems in Africa where they cannot be used. However at least three, i.e., penicillin, vaccines, and hydroxyurea, could be easily accessible in the framework of defined therapeutic strategies. If daily penicillin and pneumococcal vaccine Pneumo 23 are required, it would likely be necessary to select a conjugated vaccine other than Prevenar that does not provide protection against all strains present in Africa. Neonatal screening is still a rare procedure in sub-Saharan countries. Periodic transfusion is steadily improving but exchange transfusion programs aimed in particular at preventing neurological complications are still unfeasible. Indications for hydroxyurea therapy in Africa are more common due to the lack of access to chronic transfusion and must be based on consensus decision. Use of bone marrow transplantation, i.e., the only currently available curative treatment, is still possible only in northern hemisphere countries where it is still restricted to children with severe forms and an HLA-compatible family donor.
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PMID:[Is therapeutic progress in the management of sickle cell disease applicable in sub-Saharan Africa?]. 1830 May 25

Allogeneic blood or marrow transplantation (BMT) is potentially curative for a variety of life-threatening nonmalignant hematologic diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and hemoglobinopathies. The application of BMT to treat these disorders is limited by the lack of suitable donors and often end-organ damage from the underlying disease. We treated three patients with thrombotic PNH, one of whom also had sickle cell disease, with a nonmyeloablative, HLA-haploidentical BMT with post-transplant CY. Rapid engraftment without GVHD occurred in two of the patients, including the patient with sickle cell disease. Both patients are disease free with full donor chimerism and require no immunosuppressive therapy, with follow-up of 1 and 4 years, respectively. Nonmyeloablative, HLA-haploidentical BMT with post-transplant CY is a promising approach for patients with life-threatening nonmalignant hematologic disease who lack an HLA-matched sibling donor.
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PMID:Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. 1862 13

Reduced-intensity conditioning (RIC) regimens have the potential to decrease toxicities related to hematopoietic stem cell transplantation (HCT) in patients with sickle cell disease (SCD) and thus make HCT a more acceptable therapeutic option for this group of patients. We report the results of 7 patients enrolled on a study to evaluate safety and efficacy of HCT using bone marrow from an HLA matched sibling donor following an RIC regimen for patients with high-risk SCD. The conditioning regimen consisted of busulfan, fludarabine, equine antithymocyte globulin, and total lymphoid irradiation with shielding of the liver, lungs, heart, and gonads on day 1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The regimen was well tolerated, and all patients had hematopoietic recovery. Six of 7 patients are stably engrafted off immunosuppression and without sickle cell-related symptoms at 2 to 8.5 years after HCT. Consistent with the complete resolution of SCD related symptoms observed in the 6 engrafted patients, erythropoiesis of complete or predominantly donor origin was detected by red blood cell-specific chimerism assays, despite their having persistent mixed chimerism in the mononuclear and lymphoid compartments. These findings demonstrate the curative potential of allogeneic HCT after an RIC regimen in patients with SCD.
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PMID:Stable long-term donor engraftment following reduced-intensity hematopoietic cell transplantation for sickle cell disease. 1894 Jun 82

The beta-thalassemias and sickle cell anemia are severe congenital anemias for which there is presently no curative therapy other than allogeneic bone marrow transplantation. This therapeutic option, however, is not available to most patients due to the lack of an HLA-matched bone marrow donor. Emerging modalities based on cell engineering offer new prospects for potentially curative approaches that are applicable to more patients. The first is based on the transfer of a regulated globin gene in autologous hematopoietic stem cells (HSCs). This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid-specific, differentiation and stage-restricted, elevated, position-independent, and sustained over time. Following the original report by May et al., several groups have reported that lentiviral vectors encoding slightly different combinations of proximal and distal transcriptional control elements of the normal human beta-globin gene permit lineage-specific and elevated beta-globin expression in vivo, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Clinical studies utilizing the TNS.3 vector are likely to be initiated in the US in 2009. While the addition of the wild-type beta-globin gene is naturally suited for treating beta-thalassemia, several alternatives have been proposed for the treatment of sickle cell disease, using either gamma- or mutant beta-globin gene addition, trans-splicing or RNA interference. The recent discovery that adult somatic cells can be reprogrammed to become pluripotent stem cells from which HSCs can be derived, provides yet another venue for developing stem cell engineering using either lentiviral vectors or homologous recombination techniques. Altogether, these recent advances bode well for the advent of curative stem cell-based therapies.
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PMID:Stem cell engineering for the treatment of severe hemoglobinopathies. 1899 54

Among the cases yet published of development of vitiligo after BMT, only two can claim as possible adoptive transfer of such disease. We report a case of a patient with sickle cell disease in whom vitiligo developed after allogeneic BMT from his HLA identical father affected by vitiligo. We reviewed and searched for some particularities in the reported cases of post-BMT vitiligo.
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PMID:Possible transfer of vitiligo by allogeneic bone marrow transplantation: a case report. 1903 13

Multicenter trials have shown that hematopoietic cell transplantation (HCT) has an excellent outcome in children with sickle cell disease (SCD). As a single center, we performed a total of 11 transplants in 10 patients (6 males, 4 females) with SCD between 1997 and 2005. Eight patients had hemoglobin SS disease and two patients had HbSbeta(0) thalassemia. The median age of HCT was 10.1 (range 2.8-16.3) years. All donors were HLA-identical siblings; six patients received bone marrow (BM), two patients received mobilized peripheral blood, one patient received umbilical cord blood (UCB) and one patient received both UCB and BM from the same donor. Myeloablative conditioning regimen consisted of busulfan, horse antithymocyte globulin and cyclophosphamide. One patient had a gradual decrease in donor chimerism to 15% and subsequently received a second bone marrow transplant using a reduced intensity conditioning regimen consisting of alemtuzumab, fludarabine and melphalan leading to stable full engraftment. Currently, 9 out of 10 patients are alive with a median follow-up of 5.5 (range 2.9-11) years. As a single institution's experience with HCT in children with SCD, we report an excellent outcome, and a second HCT may be considered for patients with impending engraftment failure as a cure for SCD.
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PMID:Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience. 1978 79


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