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

Abstract

Allogeneic hematopoietic stem cell transplantation is curative for transfusiondependent 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 con-How to cite this article: Chan WYK, Kwok JSY, Chiang AKS, et al. Repeated CD45RA-depleted DLI successfully increases donor chimerism in a patient with beta-thalassemia major after haploidentical stem cell transplant. Pediatr Transplant.

Case report: HLA-haploidentical HSCT rescued with donor lymphocytes infusions in a patient with X-linked chronic granulomatous disease

“…Our case shows how important it is to monitor the lineage specific chimerism after haplo-HSCT in CGD to initiate DLI administrations. Similarly, in patients with hemoglobinopathies mixed donor chimerism and graft rejection post HSCT, regardless of the donor source, are frequently observed and may also be rescued by DLI ( 9 , 30 , 31 ). Of note, until this day no definite recommendation from the EBMT working party exists regarding the use of DLI after haplo-HSCT (6).…”

CD19+ lineage chimerism, an early biomarker after anti-CD19 CAR-T cell therapy in patients previously receiving a hematopoietic stem cell transplantation

“…HSCT is considered standard treatment for high-risk B-cell leukemia, requiring chimerism monitoring with short tandem repeats (STR) by polymerase chain reaction (PCR) to test graft function and predict patient outcome ( 2 ). Prospective studies show that patients with B-cell acute leukemia with increasing mixed chimerism have greater risk of relapse ( 3 , 4 ), thus immunosuppression withdrawal and/or administration of donor lymphocyte infusion (DLI) ( 5 ) is recommended.…”

Successful haploidentical hematopoietic stem cell transplantation (HSCT) and durable engraftment by repeated donor lymphocyte infusions for a Chinese patient with transfusion‐dependent hemoglobin (Hb) Hammersmith and massive splenomegaly

“…Use of stem cell boost and CD45RO DLI in improvement of chimerismWith massive splenomegaly, low-level donor chimerism, and prolonged cytopenia, the patient would be vulnerable to another graft rejection and various infections. Infusion of stem cell boost and donor lymphocytes served the purpose of both combating infections and improving chimerism 29. Escalating doses of unmanipulated DLIs were given when the donor CD3 chimerism was <50%.…”