Trusted Resources: Evidence & Education
Scientific literature and patient education texts
Development of a multi-center cohort to evaluate long-term outcomes and late effects following hematopoietic cell transplantation for sickle cell disease: A STAR initiative
source: American Society of Hematology
year: 2017
authors: Elizabeth Stenger, Allistair Abraham, Curtis D Travers, Hemalatha G. Rangarajan, Diane Hsu, Sonali Chaudhury, Kimberly A. Kasow, Michael J. Eckrich, Alexander I. Ngwube, Julie Kanter, Gregory M Guilcher, John T. Horan, Lakshmanan Krishnamurti, Shalini Shenoy
summary/abstract:Hematopoietic cell transplantation (HCT) is currently the only cure for sickle cell disease (SCD), with excellent survival using a matched related donor (MRD). Disease specific HCT registries have significantly advanced understanding of outcomes, via more comprehensive data collection in a larger number of patients. Such data may provide long-term outcomes after HCT, resulting in identification of advantages and disadvantages over conservative therapy, helping to focus future efforts on avoiding or improving the latter.
Methods: A multicenter retrospective registry of transplanted SCD patients was created through the Sickle Transplant Alliance for Research (STAR). Baseline, transplant, and long-term (most recent if >2 yrs from HCT, otherwise 1 yr) outcome data was collected from 10 centers. Disease recurrence was defined as acute SCD symptoms with hemoglobin S >50%. Graft rejection was defined as whole blood or myeloid donor chimerism <5%. Pulmonary function testing values were converted to functional categories per previous reports. Pre- and post-HCT values were compared using McNemar’s test and extensions. P-values <0.05 were considered statistically significant.
Results: Overall, 174 of 196 patients survived ≥1-yr post-HCT, with last assessment at 1186 d (Interquartile range, IQR: 760, 2351). Of these, 70.4% underwent HCT for clinically severe SCD from 1993-2016 (median, 2011), at 9.8±5.2 yrs (range, 1.6-25.6). Seventy-five percent (n=131) of patients received stem cells (87.0% marrow) from a MRD, and 58.1% received myeloablative conditioning, 93.7% with in vivo T cell depletion. Fourteen patients (8.1%) had rejection/disease recurrence 0.8-3.4 mo post-HCT; of these, 7 underwent a 2nd HCT. Overall, 45 patients (25.9%) developed chronic GVHD, at a median of 226 d (IQR: 140, 336), which was severe in 11 (24.4%) and extensive in 5 (11.1%). Ten patients required systemic immunosuppression 15-39 mo post-HCT, while 157 patients discontinued such at a median of 237 d (IQR: 173, 408). Donor chimerism was maintained long-term at a median of 100% in unsorted (n=101) and sorted (T: n=85, myeloid: n=69) samples, as reflected in median post-HCT hemoglobin levels of 13.0 g/dL (n=169; IQR: 11.8, 13.9). Posterior reversible encephalopathy syndrome (PRES) was reported in 18 patients (10.3%); 12 developed seizures with PRES and 9 without (12.1% with seizures). Of the 105 patients with available pre- and post-HCT brain MRIs, 2 developed new infarcts, 6 had new vasculopathy, and 10 had progression of previous infarct or vasculopathy; all but 2 of these patients had CNS disease pre-HCT . While there was no difference between pre- and post-HCT pulmonary functions (P=0.79; n=91), 10 patients normalized and 11 had deterioration. In the 13 patients with either a restrictive or obstructive pattern post-HCT, 47% had acute chest syndrome as an indication for HCT. One patient with poor cardiac function transitioned to normal function post-HCT, while 5 had a lower EF (p=0.103) and 4 a lower SF (p=0.05) post-HCT. All patients who developed an abnormal EF or SF received myeloablative conditioning (88.9%) or underwent HCT for clinically severe SCD (66.7%). Mean TR jet velocity was normal in the 64 patients that underwent this evaluation post-HCT. Immune reconstitution was robust, with median ALC 2587 (n=151; IQR: 2000, 3357) and present/normal splenic uptake on nuclear medicine scan in 90.9% (n=44). Bone age was delayed in 44.9% (n=69). Bone mineral density showed a mean spine and body Z score of -0.56 and -0.50, respectively (n=92). In post-pubertal females, 22 had normal menstruation (48.9%) and 23 menstrual irregularity (51.1%), with 13 on hormone replacement therapy; data was not obtained in 15.
organization: Emory University School of Medicine, Atlanta, GA; Children's National Medical Center, Washington, DC; Nationwide Childrens Hospital, Columbus, OH; Joseph M. Sanzari Children's Hospital, Hackensack, NJ; Ann and Robert Lurie Children's Hospital, Chicago, IL; University of North Carolina, Chapel Hill; Methodist Children's Hospital of South Texas, San Antonio, TX; Phoenix Children's Hospital, Phoenix; Medical University Of South Carolina, Charleston, SC; Alberta Children’s Hospital, Calgary, AB, Canada; Washington University in St. Louis, Saint Louis, MOread more
Related Content
-
Endari: A Treatment Option for Sickle Cell DiseaseEndari is an amino acid, approved by Foo...
-
CTX001 Continues to Show Promise in Severe SCDA single dose of CTX001, an experimental...
-
A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in childrenMagnesium, a vasodilator, anti-inflammat...
-
Gene Therapy for Blood DisordersIn the context of intense scrutiny over ...
-
Review Board Finds Global Blood’s Sickle Cell Disease Therapy Voxelotor Is SafeAn independent review board has found Gl...
-
Miai & Ama Talk About Sickle Cell Diseasehttps://www.youtube.com/watch?v=7bUFGux-...
-
SCD Patients Benefit From Early Rivipansel Treatment for VOCs, New Analyses ShowStarting treatment with rivipansel (GMI-...
To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences. More Information
The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.