Elizabeth S Allen1, Kshitij Srivastava1, Matthew M Hsieh2, Courtney D Fitzhugh3, Harvey G Klein1, John F Tisdale2, Willy A Flegel4. 1. Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA. 2. Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 3. Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 4. Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA. Electronic address: waf@nih.gov.
Abstract
BACKGROUND: Haemopoietic progenitor cell (HPC) transplantation can cure sickle cell disease. Non-myeloablative conditioning typically results in donor-derived erythrocytes and stable mixed chimerism of recipient-derived and donor-derived leucocytes. Exposure to donor antigens from the HPC graft and new red cell antibodies induced by transfusion can lead to immunohaematological complications. We assessed the incidence of such complications among HPC transplant recipients with sickle cell disease. METHODS: The study population was all patients with sickle cell disease enrolled before March 31, 2015, in the three clinical trials of non-myeloablative HPC transplantation at the National Institutes of Health. We assessed formation of new red cell antibodies after transplantation and red cell incompatibility between donors and recipients. FINDINGS: 61 patients were enrolled, 42 were HLA matched and 19 were haploidentical. Nine (15%) had immunohaematological complications. Before HPC transplantation, three patients had antibodies incompatible with their donors. After HPC transplantation, new red cell antibodies were seen in six patients (11 alloantibodies and two autoantibodies), among whom three developed antibodies incompatible with donor or recipient red cells and three developed compatible antibodies. The clinical course of complications was highly variable, from no severe effects attributable to antibodies, to sustained reticulocytopenia, to near-fatal haemolysis. We found no significant correlation between immunohaematological complications and graft failure, graft rejection, or death. INTERPRETATION: Clinical effects ranged from seemingly not clinically important to potentially fatal. In patients with sickle cell disease, donor and recipient red cell phenotypes should be carefully assessed before transplantation to minimise and manage the risk of immunohaematological complications. FUNDING: Intramural Research Program and National Institutes of Health.
BACKGROUND: Haemopoietic progenitor cell (HPC) transplantation can cure sickle cell disease. Non-myeloablative conditioning typically results in donor-derived erythrocytes and stable mixed chimerism of recipient-derived and donor-derived leucocytes. Exposure to donor antigens from the HPC graft and new red cell antibodies induced by transfusion can lead to immunohaematological complications. We assessed the incidence of such complications among HPC transplant recipients with sickle cell disease. METHODS: The study population was all patients with sickle cell disease enrolled before March 31, 2015, in the three clinical trials of non-myeloablative HPC transplantation at the National Institutes of Health. We assessed formation of new red cell antibodies after transplantation and red cell incompatibility between donors and recipients. FINDINGS: 61 patients were enrolled, 42 were HLA matched and 19 were haploidentical. Nine (15%) had immunohaematological complications. Before HPC transplantation, three patients had antibodies incompatible with their donors. After HPC transplantation, new red cell antibodies were seen in six patients (11 alloantibodies and two autoantibodies), among whom three developed antibodies incompatible with donor or recipient red cells and three developed compatible antibodies. The clinical course of complications was highly variable, from no severe effects attributable to antibodies, to sustained reticulocytopenia, to near-fatal haemolysis. We found no significant correlation between immunohaematological complications and graft failure, graft rejection, or death. INTERPRETATION: Clinical effects ranged from seemingly not clinically important to potentially fatal. In patients with sickle cell disease, donor and recipient red cell phenotypes should be carefully assessed before transplantation to minimise and manage the risk of immunohaematological complications. FUNDING: Intramural Research Program and National Institutes of Health.
Authors: Willy A Flegel; Qing Chen; Lilian Castilho; Margaret A Keller; Ellen B Klapper; William J Lane; France Pirenne; Gary Stack; Maryse St-Louis; Christopher A Tormey; Dan A Waxman; Christof Weinstock; Silvano Wendel; Gregory A Denomme Journal: Blood Transfus Date: 2018-02-14 Impact factor: 3.443
Authors: Robert Sheppard Nickel; Willy A Flegel; Sharon D Adams; Jeanne E Hendrickson; Hua Liang; John F Tisdale; Matthew M Hsieh Journal: EClinicalMedicine Date: 2020-06-28
Authors: Naoya Uchida; Matthew M Hsieh; Lydia Raines; Juan J Haro-Mora; Selami Demirci; Aylin C Bonifacino; Allen E Krouse; Mark E Metzger; Robert E Donahue; John F Tisdale Journal: Nat Commun Date: 2019-10-02 Impact factor: 14.919