Supportive health care measures instituted during childhood successfully prevent serious infections and many other life-threatening complications of sickle cell disease (SCD), resulting in improved survival to adulthood. This has, in part, shifted the demographics of SCD to include a growing proportion of young adults with chronic health impairments. While hematopoietic cell transplantation (HCT) has curative potential, very few individuals with SCD are treated by HCT, due in part to the toxicity of this treatment. Recently, advances in Human Leukocyte Antigen (HLA) typing techniques and supportive care have improved outcomes of HCT, particularly after unrelated donor HCT. A conditioning regimen of Busulfan, Fludarabine and anti-thymocyte globulin has a reduced toxicity profile and appears effective in HCT from unrelated donors in adults who have advanced myeloid malignancies and thalassemia major. We have organized an interdisciplinary group of transplant investigators and adult sickle cell providers to test the hypothesis that HCT from an HLA-identical sibling or unrelated marrow donor is safe and effective in young adults with severe SCD. We propose to test this hypothesis in a pilot investigation, which will also serve as a central planning mechanism for designing, organizing and launching a large parallel cohort clinical trial in which transplantation and supportive treatment for adults with severe SCD will be compared. Thus, we propose to investigate HCT in adults with severe sickle cell disease by the following specific aims: 1. Determine the feasibility and tolerability of HCT in young adults with severe sickle cell disease. 2. Measure the impact of donor hematopoiesis on end-organ function and define the sample size and clinical endpoints of a larger comparative clinical trial. If successfully planned and initiated, the proposed comparative clinical trial would be the first to compare HCT and supportive care for SCD, and could broaden the therapeutic opportunities for adults with severe SCD.

Public Health Relevance

Sickle cell disease progresses rapidly during adulthood leading to damage to various organs and premature mortality and there are no good treatments available to prevent the progression of disease. While bone marrow transplantation is known to be effective in pediatric patients, it's place in the management of the disease is unclear and has not been systematically studied in adults. We propose to conduct a pilot multi-center study of BMT for patients 16-40 years of age to determine the safety and tolerability of this treatment and facilitate the planning of a large scale trial to determine place of BMT in adults with sickle cell disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Planning Grant (R34)
Project #
1R34HL108761-01
Application #
8144621
Study Section
Special Emphasis Panel (ZHL1-CSR-D (M2))
Program Officer
Luksenburg, Harvey
Project Start
2011-09-01
Project End
2014-06-30
Budget Start
2011-09-01
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$295,408
Indirect Cost
Name
University of Pittsburgh
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Walters, Mark C; De Castro, Laura M; Sullivan, Keith M et al. (2016) Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease. Biol Blood Marrow Transplant 22:207-211
Walters, Mark C (2015) Update of hematopoietic cell transplantation for sickle cell disease. Curr Opin Hematol 22:227-33