231. Mixed Chimerism After Allogeneic Hematopoietic Stem Cell Transplantation in Sickle Cell Disease: Preliminary Results on Peripheral Blood Sorted Subpopulations and Erythroid Progenitors
Authors: Alessandra Magnani, Laure Caccavelli, Mathieu Fusaro, Jeremy Magalon, Elisa Magrin, Emmanuelle Six, Fabien Touzot, Chloé Couzin, Jean Antoine Ribeil, Cécile Arnaud, Corinne Pondarré, Annie Kamdem, Françoise Bernaudin, Jean Paul Vernant, Eliane Gluckman, Dominique Bories, Marina Cavazzana
Journal: Molecular Therapy (2016)

Introduction: Patients with sickle cell disease (SCD) may develop a persistent mixed chimerism (MC) after hematopoietic stem cell transplantation (HSCT) associated with clinical control of the disease. In order to further investigate this condition we analyzed the chimerism in sorted myeloid and lymphoid subpopulations, and erythroid progenitors. Methods: Between 1990 and 2013, 112 sickle cell disease (SCD) patients underwent allogeneic HSCT after myeloablative conditioning. Among the 107 patients with available chimerism at 2 years, 55.1% had a MC, i.e. <95% of cells from donor origin on white blood cells (WBCs). Myeloid (CD14+, CD15+) and lymphoid (CD3+, CD19+) subpopulations, erythroid burst-forming units (BFU-E) and granulocyte monocyte colony forming units (CFU-GM) were analyzed in patients presenting with MC, follow-up ≥1 year and the hemoglobin (Hb) profile comparable to their donors'. High performance liquid chromatography (HPLC) analysis was performed on whole blood. Results: Thirty patients were included. Preliminary results from 13 patients with clinical control of the disease reveal heterogeneous patterns of subpopulation chimerism (table). A significant discrepancy in chimerism measured in WBCs compared to the other populations is observed. Patients were divided into two groups according to the difference in the donor chimerism between the CD3+ and in the myeloid compartment. This difference in donor chimerism in CD3+ cells might be explained by the expansion of recipient's memory T cells after transplantation and/or a specific T-cell progenitor engraftment in these patients. Interestingly, a trend to a lower percentage of donor chimerism in the BFU-E than in the peripheral erythroid compartment is observed. Conclusions: These data show that the chimerism analysis on total WBCs is a poor indicator of the myeloid and erythroid engraftment in SCD patients. Chimerism study on sorted subsets and erythroid progenitors allows a more exhaustive investigation. Further analyses on T cells compartment are necessary to complete this information. Results in BFU-E as compared to the peripheral erythroid compartment suggest a selective genetically modified CD34+ cells. Tabled 1Pt IDDonor phenotypeMonths post HSCTHb (g/dl)HbA (%)HbS (%)HbA2 (%)HbF (%)Whole bloodCD3+CD14+CD15+CD19+BFU-ECFU-GM1AA2114.284.50nana6640.598.5>9590nana6AA9111.893.83.13.10191223311337.5577AS15513.556.5412.60583471na4975604AS13210.65433.3nana5344444658323717AS1311.547.841.23.21.48575na9273837618A/Dpubjab8012.647.90nana887795959494.59912A/b0Thal579.69503291689698999910011AA5413.49703088781001009998985AA3410.978.38nana444641na5058432AS468.42468.1nana21709.45.43112.5na8AS1339.734.7632.401631121013089AS1539.552.145.920183026161117153AA3310.189.553.22.330631718231317 Open table in a new tab