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Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases.

ABSTRACT: Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029-$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time.

SUBMITTER: Arnold SD

PROVIDER: S-EPMC5664386 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases.

Arnold Staci D SD Brazauskas Ruta R He Naya N Li Yimei Y Aplenc Richard R Jin Zhezhen Z Hall Matt M Atsuta Yoshiko Y Dalal Jignesh J Hahn Theresa T Khera Nandita N Bonfim Carmem C Majhail Navneet S NS Diaz Miguel Angel MA Freytes Cesar O CO Wood William A WA Savani Bipin N BN Kamble Rammurti T RT Parsons Susan S Ahmed Ibrahim I Sullivan Keith K Beattie Sara S Dandoy Christopher C Munker Reinhold R Marino Susana S Bitan Menachem M Abdel-Azim Hisham H Aljurf Mahmoud M Olsson Richard F RF Joshi Sarita S Buchbinder Dave D Eckrich Michael J MJ Hashmi Shahrukh S Lazarus Hillard H Marks David I DI Steinberg Amir A Saad Ayman A Gergis Usama U Krishnamurti Lakshmanan L Abraham Allistair A Rangarajan Hemalatha G HG Walters Mark M Lipscomb Joseph J Saber Wael W Satwani Prakash P

Haematologica 20170817 11

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes <i>and</i> decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox mod ...[more]

PMID: 28818869

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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.

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:IMPORTANCE:Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant. OBJECTIVE:To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia. DESIGN, SETTING, AND PARTICIPANTS:From July 16, 2004, to October 25, 2013, 30 patients aged 16-65 years with severe disease enrolled in this nonmyeloablative transplant study, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells (5.5-31.7?×?10(6) cells/kg) from human leukocyte antigen-matched siblings. MAIN OUTCOMES AND MEASURES:The primary end point was treatment success at 1 year after the transplant, defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia. The secondary end points were the level of donor leukocyte chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell-thalassemia disease-free survival, immunologic recovery, and changes in organ function, assessed by annual brain imaging, pulmonary function, echocardiographic image, and laboratory testing. RESULTS:Twenty-nine patients survived a median 3.4 years (range, 1-8.6), with no nonrelapse mortality. One patient died from intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. The mean donor T-cell level was 48% (95% CI, 34%-62%); the myeloid chimerism levels, 86% (95% CI, 70%-100%). Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease. The normalized hemoglobin and resolution of hemolysis among engrafted patients were accompanied by stabilization in brain imaging, a reduction of echocardiographic estimates of pulmonary pressure, and allowed for phlebotomy to reduce hepatic iron. The mean annual hospitalization rate was 3.23 (95% CI, 1.83-4.63) the year before, 0.63 (95% CI, 0.26-1.01) the first year after, 0.19 (95% CI, 0-0.45) the second year after, and 0.11 (95% CI, 0.04-0.19) the third year after transplant. For patients taking long-term narcotics, the mean use per week was 639 mg (95% CI, 220-1058) of intravenous morphine-equivalent dose the week of their transplants and 140 mg (95% CI, 56-225) 6 months after transplant. There were 38 serious adverse events: pain and related management, infections, abdominal events, and sirolimus related toxic effects. CONCLUSIONS AND RELEVANCE:Among 30 patients with sickle cell phenotype with or without thalassemia who underwent nonmyeloablative allogeneic HSCT, the rate of stable mixed-donor chimerism was high and allowed for complete replacement with circulating donor red blood cells among engrafted participants. Further accrual and follow-up are required to assess longer-term clinical outcomes, adverse events, and transplant tolerance. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00061568.

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Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases.

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Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases.

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