Unrelated Umbilical Cord Blood Transplant for Children with β-Thalassemia Major

Abstract

Beta thalassemia major, one of the most prevalent hemoglobinopathy throughout the word, can be cured by allogenic stem cell transplantation (SCT) (Bone Marrow Transplant 36:971-975, 2005). Many patients, however, lack a suitably matched related sibling donor. Unrelated umbilical cord blood (UCB) can be used as an alternative stem cell source for these patients. This report describes SCT for nine children with beta-thalassemia major using partially HLA-matched unrelated UCB. Conditioning included oral busulfan 16 mg/kg (day -10 to -7), cyclophosphamide (Cy) 200 mg/kg (day -5 to -2), fludarabine 90 mg/kg (day -13 to -11), and antithymocyte globulin (rabbit) 7.5 mg/kg (day -3 to -1). The infused cell dose was 10.71 × 10(7)/kg total nucleated cells (TNC) (range 6.5-17 × 10(7)/kg TNC). The patients ranged in age from 1.5 to 7 years, in weight from 10.5 to 17 kg. A second transplant with two unrelated cord blood units was attempted in two patients who had primary graft failure. The retransplant recipients were preconditioned with i.v Cy 120 mg/kg (day -3 to -2). Five of the nine patients engrafted promptly with 50-100 % donor chimerism (56 %). They engrafted at a median of 17 days (range 12-19). One patient is transfusion free for 36 months; a second patient is transfusion free for 18 months and a third is transfusion free for 9 months. There was no transplant related mortality. Four of the nine children had autologous recovery without engraftment. Primary graft rejection is the major complication. Post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade II, and CMV interstitial pneumonia. The chronic GVHD was limited and could be controlled by Methylprednisolone combined with Mycophenolate. The lack of a marrow donor registry in India makes UCBT from related and unrelated donors a good alternative. Transplant should be delayed until the child is at least 18 months of age. The dose of UCB stem cells is the most important factor for engraftment. UCB has the advantages of rapid availability and low risk of severe GVHD despite donor-recipient HLA disparity (Transplant Proc 37:2667-2669, 2005). We demonstrate the feasibility of this procedure in the setting of a developing country.

Combination of a triple alpha-globin gene with beta-thalassemia in a gypsy family: importance of the genetic testing in the diagnosis and search for a donor for bone marrow transplantation for one of their children

“…Still, the only curative treatment for the disease is hematopoietic stem cell transplantation. Subjects who have an HLA-identical healthy sibling are candidates for transplantation, although if this is not the case, at present unrelated donor transplant outcomes are very promising, expanding the possibilities for these patients [ 10 , 11 ].…”

Double‐unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA‐identical sibling bone marrow transplantation

“…Strategies aimed at overcoming the low cell content of single cord blood unit include cotransplantation of multiple units. 10 However, EF was still the main cause of treatment failure, improved results were observed by Jaing et al 11 in nine TM patients using a double-unit UCBT approach with only one patient developed secondary EF. TT possesses both myeloablative and immunosuppressive properties, and a preparative regimen of TT, Bu, and Cy has been shown to provide sustained engraftment in patients with genetic diseases after T cell-depleted allo-BMT.…”

“…However, these advantages are counter‐balanced by the disadvantages of increased risk of graft rejection and delayed hematopoietic recovery after HSCT, and the risk is partially related to the reduced stem cell dose. Strategies aimed at overcoming the low cell content of single cord blood unit include cotransplantation of multiple units 10 . However, EF was still the main cause of treatment failure, improved results were observed by Jaing et al 11 in nine TM patients using a double‐unit UCBT approach with only one patient developed secondary EF.…”

Hematopoietic Stem Cell Transplantation in Children With Hemoglobinopathies: Brazilian Society of Bone Marrow Transplantation Consensus

“…Data with unrelated umbilical cord blood, although restricted, resulted in high graft failure rates and, consequently, reduction in overall survival 17,18 . For this reason, we do not recommend the use of unrelated umbilical cord blood.…”