Abstract
Allogeneic cord blood transplantation (CBT) is increasingly used in children with beta-thalassemia major. Donor/recipient mixed chimerism (MC) is frequently observed in patients with beta-thalassemia major given bone marrow transplantation (BMT) in the early post-transplant period, due to the persistence of haematopoietic and immune cells of host origin. Previous clinical data reported on these patients demonstrated that the majority of them exhibiting MC convert to full donor chimerism (FDC), some maintain MC stable over time, while a non negligible number of patients develop graft failure, in particular when increasing proportions of cells of host origin are observed in serial monitoring. Aims of the present study were to retrospectively investigate the proportion of children with beta-thalassemia major experiencing either transient, or long-lasting persistence of hematopoietic cells of host origin after CBT, as compared to those given BMT, and to analyze the relationship existing between the evolution of MC over time and clinical outcome. One hundred and six consecutive patients, 27 given CBT from an HLA-identical related donor (RD) and 79 given BMT (42 from a RD and 37 from an HLA-compatible unrelated volunteer, UD), were enrolled in the study. Donor/recipient chimerism status was evaluated by PCR-based assay, analyzing selected polymorphic short tandem repeat (STR) loci. CBT and BMT recipients received similar preparative regimens. Anti-thymocyte globulin (ATG 10 mg/Kg on days −4, −3 and −2; Fresenius, Graefelfing, Germany) was used in all patients given an UD-BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (Cs-A) alone in CBT recipients; either CsA alone (12 RD-BMT recipients) or CsA in combination with methotrexate (MTX) was given to BMT patients. All patients given CBT engrafted and displayed MC early after transplantation, 13/27 converted to FDC (6 within 1 month and 7 within 1 year after CBT), 14/27 maintained stable MC, and all of them are alive, transfusionin-dependent and free of any immune-suppressive drug, the follow-up ranging between 15 and 89 months (median value 42 months). In the group of children given BMT, 24/79 (12 transplanted from UD and 12 from RD) exhibited FDC at all time points examined, 4/79 (1 transplanted from UD and 3 from RD) did not engraft and 51/79 (23 from UD and 28 from RD) displayed MC at time of haematological reconstitution. Forty out of these 51 BMT recipients with MC status converted to FDC (17 from UD and 23 from RD; 29 within 1 month and 11 within 1 year after BMT), 3/51 maintained stable MC (1 undergoing UD- and 2 RD-BMT), while 8/51 (5 from UD and 3 from RD) progressively lost the graft, returning to be transfusion-dependent. The median follow-up time was 51 months (range: 15–110 months) and 48 months (range: 16–81 months) in the RD-BMT and UD-BMT group, respectively. None of the patients given CBT experienced either grade II-IV acute GVHD, which was, by contrast, diagnosed in 3 and 7 patients given RD- and UD-BMT, respectively. Chronic GVHD was diagnosed in 8 children (2 from RD- and 6 from UDBMT). Five out of 106 pediatric patients enrolled in the study, 2 included in the RD-BMT and 3 in the UD-BMT group, died of transplantation-related complications. These results indicate that MC is frequently observed in children with beta-thalassemia after RD-CBT, without, however, predicting an increased risk of treatment failure. CBT from an HLA-identical related donor is a successful option in beta-thalassemia major, possibly also due to the establishment of an effective state of immune tolerance between host and donor that decreases the risk of both graft rejection and GVHD.
Newborn Screening Practices for Beta-Thalassemia in the United States
