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Dr. Hemalatha Rangarajan and colleagues from Nationwide Children’s Hospital in Columbus, Ohio, published an exciting case series of post-transplant cyclophosphamide graft-versus-host disease (GvHD) prophylaxis in sickle cell disease patients with matched unrelated donors. The findings were published in the Biology of Blood and Marrow Transplantation, February 2018 edition.
Matched related donor transplant has historically shown excellent outcomes in sickle cell disease patients, however, less than 20% of patients in this population have a matched related donor. Based on the need to use unrelated or haploidentical donors in sickle cell, finding safe and effective methods to prevent GvHD is clinically important for optimal patient outcomes.
This study used a single dose of cyclophosphamide on Day 3, combined with ongoing tacrolimus and mycophenolate immunosuppression. The prep regimen consisted of 16 doses of busulfan, 6 doses fludarabine and 3 doses rabbit anti-thymocyte globulin. All patients had 9/10 or greater matched unrelated donors, with bone marrow stem cell product. Goals of the study were to measure 1-year survival and transplant outcomes, including acute and chronic GvHD and regimen toxicity.
This case series of 4 patients presents very promising results for using post-transplant cyclophosphamide GVHD prophylaxis in unrelated donor sickle cell patients. This data presents outstanding 1-year survival outcomes and a reasonable toxicity profile. This also highlights the safety of single-dose cyclophosphamide in a population that may have pre-transplant hepatic pathology due to the sequela of severe sickle cell disease. This is a potentially valuable treatment approach, which warrants further study.
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