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Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease.

ABSTRACT: Cardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had RBCx within 3 months before HSCT. Echocardiograms and laboratory parameters were obtained at baseline, and at 3, 6, and 12 months following HSCT. Although hemolytic parameters and anemia improved following RBCx, there was a small increase in left ventricular volume index. Following successful HSCT, however, there were significant improvements in cardiac size, function, and diastolic filling parameters at 3 months followed by continued smaller improvements up to 1 year. There was a significant improvement in N-terminal pro B-type natriuretic peptide levels and a trend toward improvement in 6-minute walk time 1 year after HSCT. The magnitude of cardiac improvement seen following HSCT was comparable to that observed following correction of a volume overload state as seen in pregnancy or after repair of chronic valvular regurgitation. Further studies in sickle cell disease patients will help delineate which cardiac complications and what level of severity should be considered indications for HSCT.

SUBMITTER: Sachdev V

PROVIDER: S-EPMC6784516 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease.

Sachdev Vandana V Hsieh Matthew M Jeffries Neal N Noreuil Anna A Li Wen W Sidenko Stanislav S Hannoush Hwaida H Limerick Emily E Wilson Delon D Tisdale John J Fitzhugh Courtney C

Blood advances 20191001 19

Cardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had ...[more]

PMID: 31578191

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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.

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Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease.

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Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease.

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