Donor Lymphocyte Infusions to Displace Residual Host Hematopoietic Cells after Allogeneic Bone Marrow Transplantation for β-Thalassemia Major

Abstract

This case report shows that DLI can effectively eradicate host stem cells in mixed chimeras after BMT in nonmalignant hematopoietic diseases.

Haematopoietic stem cell transplantation for thalassaemia major in Hong Kong: prognostic factors and outcome

“…21 The use of donor leukocyte infusions should be carefully considered in patients with stable chimerism since the treatment may be associated with significant risks. 22 In conclusion, BMT for Chinese TM patients has a similar outcome as for Caucasian patients. Older age is associated with treatment failure, and transplantation should be performed early if HLA-identical siblings are available.…”

Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease

“…21,[29][30][31] The rationale here is that transient maximal immunosuppression achieved by non-myeloablative agents such as Flu and ATG suffices to ensure stable engraftment with partial, if not complete, chimerism and a state of bilateral tolerance. 21 Once this state is achieved, donor alloreactive T cells may be used against residual malignant or genetically abnormal stem cells in order to achieve complete chimerism [22][23][24] without megadoses of chemoradiotherapy. DLI has previously been shown by us to convert partial chimerism to full donor chimerism in children with genetic disease, [22][23][24] and may also be suitable for increasing engraftment of genetically engineered cells following gene therapy, which has recently been attempted in CGD.…”

“…21 Once this state is achieved, donor alloreactive T cells may be used against residual malignant or genetically abnormal stem cells in order to achieve complete chimerism [22][23][24] without megadoses of chemoradiotherapy. DLI has previously been shown by us to convert partial chimerism to full donor chimerism in children with genetic disease, [22][23][24] and may also be suitable for increasing engraftment of genetically engineered cells following gene therapy, which has recently been attempted in CGD. 6,32 This approach is especially suitable for children with genetic diseases, where it has been demonstrated that agents with adequate anti-lymphoid and anti-hematopoietic stem cell activity are necessary in order to achieve complete donor lymphoid and hematopoietic stem cell engraftment.…”

“…21 We have also shown that where only partial donor chimerism occurs, it is possible to achieve complete chimerism by administration of donor lymphocyte infusions (DLI) after transplantation. [22][23][24] We now wish to present the case of a 6-year-old child with CGD, recurrent pulmonary infections, pulmonary disability, and failure to thrive, who underwent alloPBSCT after non-myeloablative conditioning, achieving partial chimerism with no transplant-related toxicity. The child subsequently received DLI, and achieved complete donor chimerism.…”

Recurrence of β-thalassemia major more than 20 years after HLA-identical sibling BMT treated successfully with donor lymphocyte infusion

“…4,5 Although donor lymphocyte infusion (DLI) is an effective treatment for late recurrence of some hematological malignancies after allogeneic BMT, 6 DLI has only been reported in few cases for early graft failure in thalassemia. 7,8 We report a case of late recurrent b-thalassemia major successfully treated with DLI 23 years after BMT. The patient signed institutional review board-approved consent to allow his medical records to be used for research.…”