Prediction, management, and prognosis of mixed chimerism after hematopoietic stem cell transplantation in transfusion‐dependent pediatric thalassemia patients

Abstract

Background: Early-onset mixed chimerism (MC) with a high proportion of residual host cells is considered a signal of graft rejection in patients undergoing allogenic hematopoietic stem cell transplantation for transfusion-dependent thalassemia. In order to prevent graft rejection and minimize the risk of treatment-related graft-versus-host disease (GVHD), we established a hierarchical management system based on chimerism analysis. Method: This retrospective study provides a comprehensive review of the characteristics, interventions, and outcomes of the 38 patients who developed MC after transplantation among the 144 pediatric thalassemia patients between July 2007 and January 2019 at our center. Results: A sibling donor, a blood type-matched donor, conditioning regimens without fludarabine, and transplants containing <10 × 10 8 total nucleated cells/kg were identified to be associated with the development of MC. Among the 38 patients developing MC, only four patients rejected the grafts. The response rate to donor lymphocyte infusion (DLI, only for patients receiving sibling donor transplantation) and cytokine immunomodulation without DLI was 70.6% and 42.9%, respectively. Patients that developed GVHD after DLI or cytokine therapy had a more significant increase in donor cell chimerism (16%, range 0%-35%) than those without (8.5%, range −21% to 40%, P = .049). However, even when treatment-related GVHD was included, patients with MC had a lower cumulative incidence of total acute GVHD than patients with complete donor chimerism (29.2% vs 48.0%, P = .030). Conclusions: Interventions based on chimerism analysis were effective in preventing graft rejection and did not increase treatment-related GVHD in thalassemia patients with MC.

HLA-identical sibling hematopoietic stem cell transplantation following reduced-toxicity myeloablative conditioning regimen in sickle cell disease

“…Stable mixed chimerism greater than 25% is su cient to keep the patient free of sickle cell symptoms 48 , but progressive decline of the donor chimera may lead to secondary graft failure. Data from thalassemia major transplants have shown improvement of donor chimera after donor lymphocyte infusions (DLI) and the authors propose a treatment algorithm based on percentage of donor chimerism and time after HSCT 49 . At our center, we have administered DLI in four cases of secondary graft failure without success, which is in accordance with other reports 50 .…”

Non-relapse cytopenias following allogeneic stem cell transplantation, a case based review

“…The frequency of mixed chimerism in alloSCT populations is dependent on certain variables. RIC regimens are frequently associated with the development of mixed chimerism [59,60] and up to 50% of patients conditioned with RIC alloSCT demonstrate mixed chimerism [61].The degree of HLA-matching between recipient and donor may also be associated with mixed chimerism, however the relationship is controversial with some cohorts reporting an increased risk of mixed chimerism with increasing disparity [62] and some reporting the opposite [63]. Another risk factor for mixed chimerism includes a non-malignant indication for transplantation, which may reflect both a lack of immunosuppressive prior therapy compared to more common indications such as AML and frequent use of RIC [64].…”