Dataset Information

Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease.

ABSTRACT: Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications have occurred, and once patients experience significant organ damage, they are considered poor candidates for HSCT. In turn, patients who have experienced long-term organ toxicity from SCD such as renal or liver failure may be candidates for solid-organ transplantation (SOT); however, the transplanted organs are at risk of damage by the original disease. Thus, dual HSCT and organ transplantation could simultaneously replace the failing organ and eliminate the underlying disease process. Advances in HSCT conditioning such as reduced-intensity regimens and alternative donor selection may expand both the feasibility of and potential donor pool for transplantation. This review summarizes the current state of HSCT and organ transplantation in SCD and discusses future directions and the clinical feasibility of dual HSCT/SOT.

SUBMITTER: Hosoya H

PROVIDER: S-EPMC5851417 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease.

Hosoya Hitomi H Levine Jeffrey J Abt Peter P Henry David D Porter David L DL Gill Saar S

Blood advances 20180301 5

Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications ...[more]

PMID: 29535106

Similar Datasets

Project description:BackgroundSickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review.ObjectivesTo determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of the Cochrane Library) and quarterly searches of MEDLINE. We also searched trial registries for ongoing trials up to April 2020. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 December 2019.Selection criteriaRandomized controlled and quasi-randomized trials that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting.Data collection and analysisNo trials were eligible for inclusion in the review.Main resultsWe identified 12 potentially-eligible trials by the searches; we excluded 11 of these and the remaining trial is an ongoing trial that may be eligible for inclusion in a future version of the review.Authors' conclusionsReports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. We did not find any eligible randomized controlled trials assessing the benefit or risk of hematopoietic stem cell transplantations. However, there is an ongoing quasi-randomized trial comparing hematopoietic stem cell transplantation with standard care, Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease.

Project description:Sickle cell disease (SCD) is a severe autosomal recessively inherited disorder of the red blood cell characterized by erythrocyte deformation caused by the polymerization of the abnormal hemoglobin, which leads to erythrocyte deformation and triggers downstream pathological changes. These include abnormal rheology, vaso-occlusion, ischemic tissue damage, and hemolysis-associated endothelial dysfunction. These acute and chronic physiologic disturbances contribute to morbidity, organ dysfunction, and diminished survival. Hematopoietic cell transplantation (HCT) from HLA-matched or unrelated donors or haploidentical related donors or genetically modified autologous hematopoietic progenitor cells is performed with the intent of cure or long-term amelioration of disease manifestations. Excellent outcomes have been observed following HLA-identical matched related donor HCT. The majority of SCD patients do not have an available HLA-identical sibling donor. Increasingly, however, they have the option of undergoing HCT from unrelated HLA matched or related haploidentical donors. The preliminary results of transplantation of autologous hematopoietic progenitor cells genetically modified by adding a non-sickling gene or by genomic editing to increase expression of fetal hemoglobin are encouraging. These approaches are being evaluated in early-phase clinical trials. In performing HCT in patients with SCD, careful consideration must be given to patient and donor selection, conditioning and graft-vs.-host disease regimen, and pre-HCT evaluation and management during and after HCT. Sociodemographic factors may also impact awareness of and access to HCT. Further, there is a substantial decisional dilemma in HCT with complex tradeoffs between the possibility of amelioration of disease manifestations and early or late complications of HCT. The performance of HCT for SCD requires careful multidisciplinary collaboration and shared decision making between the physician and informed patients and caregivers.

Dataset Information

Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease.

Publications

Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets