Repeated CD45RA-depleted DLI successfully increases donor chimerism in a patient with beta-thalassemia major after haploidentical stem cell transplant.

Publisher: Munksgaard Country of Publication: Denmark NLM ID: 9802574 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-3046 (Electronic) Linking ISSN: 13973142 NLM ISO Abbreviation: Pediatr Transplant Subsets: MEDLINE

Original Publication: Copenhagen ; Malden, MA : Munksgaard, c1997-

Chimerism* ; Leukocyte Common Antigens*; Hematopoietic Stem Cell Transplantation/*methods ; Salvage Therapy/*methods ; T-Lymphocytes/*transplantation ; Transplantation, Haploidentical/*methods ; beta-Thalassemia/*therapy; Bone Marrow Transplantation ; Child, Preschool ; Female ; Graft Rejection ; Humans ; beta-Thalassemia/genetics ; beta-Thalassemia/immunology

Allogeneic hematopoietic stem cell transplantation is curative for transfusion-dependent thalassemia, but mixed chimerism (MC) may herald graft rejection. We report a child who failed bone marrow transplant (BMT) from matched unrelated donor (MUD) successfully salvaged with haploidentical peripheral blood stem cell transplant (PBSCT), but had MC in T-lymphocyte compartment despite near-complete donor chimerism in myeloid compartment. MC was successfully improved by repeated CD45RA-depleted donor lymphocyte infusion (DLI). A 2-year-old Chinese girl with beta-thalassemia major underwent 12/12-MUD BMT with HU/AZA/Cy/Flu/Bu/TT conditioning resulted in graft rejection. As donor refused second donation, rescue haploidentical PBSCT was performed with alemtuzumab/fludarabine/treosulfan conditioning. Harvest product was CD3/CD45RA depleted with extra products cryopreserved. Split cell chimerism performed 1-month after haplo-transplant showed 97% mother, 3% MUD, and 0% host for granulocytes but 38% mother, 62% MUD, and 0% host for CD3 + T cells. In view of low haploidentical donor chimerism in T-lymphocyte compartment, CD45RA-depleted DLI using cryopreserved product was performed on day + 38, after thymoglobulin 3 mg/kg given as T-cell depletion 3 days beforehand. T-cell chimerism improved to 51% mother and 49% MUD post-DLI. Second cryopreserved CD45RA-depleted DLI was given 17 days after the first DLI (day + 55), and 100% full chimerism of mother's T cells was gradually established without significant graft-versus-host disease (GVHD) or viral reactivation. To conclude, split lineage chimerism determination is beneficial to guide management strategy. For MC in T-cell compartment, CD45RA-depleted DLI is a potential alternative to unselected T cells as it carries lower risk of GVHD and infection.
(© 2020 Wiley Periodicals LLC.)

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Keywords: beta-thalassemia; bone marrow transplantation; chimerism; hematopoietic stem cell transplantation; lymphocyte transfusion; peripheral blood stem cell transplantation

EC 3.1.3.48 (Leukocyte Common Antigens)

Date Created: 20201214 Date Completed: 20220201 Latest Revision: 20220201

20240829

10.1111/petr.13945

33314508