{"id":16297,"date":"2020-10-14T20:43:31","date_gmt":"2020-10-14T20:43:31","guid":{"rendered":"https:\/\/www.sc101.org\/?p=16297"},"modified":"2020-10-14T20:43:31","modified_gmt":"2020-10-14T20:43:31","slug":"transplant-versus-current-standard-of-care-for-sickle-cell-disease","status":"publish","type":"post","link":"https:\/\/www.sc101.org\/transplant-versus-current-standard-of-care-for-sickle-cell-disease\/","title":{"rendered":"Transplant versus Current Standard of Care for Sickle Cell Disease"},"content":{"rendered":"<p>The decision to perform a progenitor cell transplant (bone marrow transplant) for sickle cell disease is based on the historical context that <a href=\"https:\/\/www.sc101.org\/\">sickle cell disease<\/a> is life-threatening, and historically (prior to the use of hydroxyurea and chronic red blood cell transfusions) there have been no options for medical therapies that will decrease the progression of the disease and prolong life.<\/p>\n<p>Traditionally, myeloablative conditioning (using chemotherapy to completely kill all the hematopoietic dividing cells in the bone marrow and throughout the body) and matched sibling donor (full brother or sister of the person with sickle cell disease) progenitor cell transplant has been the primary option to cure children with sickle cell disease; however, successful transplantation has been linked to long-term toxicities for some survivors, including but not limited to, severe chronic graft-versus-host disease and sterility. The publication in 2015 of the multicenter, reduced-intensity, matched sibling donor transplantation trial conducted by Dr. Allison A. King and colleagues at eighteen centers has provided critical data which advances our knowledge about progenitor cell transplant and its role for selected children with sickle cell disease and thalassemia.1<\/p>\n<p>This study was conducted to determine whether progenitor cell transplantation using immunoablative (using medication that would decrease an immune response without completely eliminating all of the hematopoietic cells) reduced intensity therapy along with a matched sibling donor. Over 12 years, a total of 43 children with SCD and nine with thalassemia received matched sibling donor with this reduced-intensity conditioning that included three drugs (alemtuzumab, fludarabine, and melphalan). The overall (sickle cell and thalassemia) survival was 94.2 % and the event-free survival (no major adverse complications) 92.3 %, with a median follow-up of 3.42 years. For sickle cell disease by itself, the survival was 93% and the event-free survival was 90.7%. After one year, no transplanted person was on immunosuppression and no graft versus host disease or rejection was noted. For sickle cell disease, there were no new events (strokes, vaso-occlusive pain episodes, or pulmonary complications).<\/p>\n<p>This study offers promise for children with sickle cell disease and a matched sibling donor to be able to receive an immunoablative reduced-intensity transplant. Though this is encouraging the study falls short of becoming standard care for this population due to unanswered questions:<\/p>\n<ul>\n<li>The median follow-up of 3.4 years prevents the assessment of long-term complications, such as infertility, and the absence of the evaluation end-organ function dampens confidence about long term end-organ disease progression after transplant.<\/li>\n<li>The biggest limitation is the lack of a comparison group of children with sickle cell disease receiving current medical therapy. For children with sickle cell disease current advances in supportive therapy provide reasonable options to delay transplant until a clinical trial is completed comparing the short- and long-term complications of the transplant regimen to a comparable group of children receiving maximum medical therapy, the burden and progression of end-organ damage may justify transplantation when compared to current therapy.<\/li>\n<\/ul>\n<p>When the trial by Dr. King and colleagues started in 2003, hydroxyurea had not been recommended as standard care for children with SCD, but it is now recommended to offer therapy at nine months. In 2003, many hematologists elected to offer hydroxyurea therapy to those children with severe disease, with criteria similar to entry criteria for the transplant trial.<\/p>\n<p>Recently two large pediatric sickle cell trials using current therapy have been completed. In one prospective study, (prospective: children were enrolled, treated and followed over time), 185 children receiving hydroxyurea, with a median duration of treatment of 10.3 years, had a 15-year survival of more than 98 percent.2 In the second retrospective study, (retrospective: medical records are reviewed for children on therapy) 1,033 children with sickle cell disease were reviewed over an approximately 6.7 year period.3 They had a survival estimate over a five-year period of more than 98 percent. These two large pediatric sickle cell disease studies provide inconvertible evidence that sickle cell disease in children is no longer a life-threatening disease, but a chronic disease that may have life-threatening episodes.<\/p>\n<p>The multi-institutional reduced-intensity conditioning and matched sibling transplant trial provides reasonable evidence for advancing the care of children with sickle cell disease. However, the results fall short of recommending that this transplant strategy should become the standard of care for sickle cell disease in children.<\/p>\n<p>To advance the treatment of children with sickle cell disease, the next reduced-intensity conditioning transplant trial requires a longer follow-up duration, evaluation of end-organ disease, assessment of fertility, and a comparison group receiving maximum medical therapy. Questions regarding the optimal reduced-intensity transplant for children with sickle cell disease deserve to be answered in a comparison study. The work by Dr. King and colleagues brings us one step closer to finding that definitive answer.<\/p>\n<ol>\n<li>King AA, Kamani N, Bunin N, et al. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol 2015;90:1093-8.<\/li>\n<li>Le PQ, Gulbis B, Dedeken L, et al. Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment. Pediatr Blood Cancer 2015;62:1956-61.<\/li>\n<li>Couque N, Girard D, Ducrocq R, et al. Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines. Br J Haematol 2016;173:927-37.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>The decision to perform a progenitor cell transplant (bone marrow transplant) for sickle cell disease is based on the historical context that sickle cell disease is life-threatening, and historically (prior&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"inline_featured_image":false,"footnotes":""},"categories":[8],"tags":[],"acf":[],"_links":{"self":[{"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/posts\/16297"}],"collection":[{"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/comments?post=16297"}],"version-history":[{"count":0,"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/posts\/16297\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/media?parent=16297"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/categories?post=16297"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.sc101.org\/wp-json\/wp\/v2\/tags?post=16297"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}