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Severe combined immunodeficiency: treatment by bone marrow transplantation in 15 infants using HLA-haploidentical
Insights
Bone marrow transplantation (BMT) from matched parents successfully restored immune function in infants with severe combined immunodeficiency (SCID). T-cell depletion prevented graft-versus-host disease (GvHD), enabling immune reconstitution in most patients.
Area of Science:
- Immunology
- Hematology
- Pediatrics
Background:
- Severe combined immunodeficiency (SCID) is a group of rare genetic disorders characterized by profound defects in T-cell and B-cell immunity.
- Bone marrow transplantation (BMT) is a potential curative therapy for SCID, but graft-versus-host disease (GvHD) remains a significant complication, especially with HLA-haplo-identical grafts.
Purpose of the Study:
- To evaluate the efficacy and safety of T-cell-depleted, HLA-haplo-identical BMT in infants with SCID.
- To assess the need for cytoreductive conditioning prior to transplantation.
Main Methods:
- Fifteen infants with SCID underwent BMT from HLA-haplo-identical parents.
- Marrow grafts were depleted of T-lymphocytes using lectin agglutination and rosette formation.
- Thirteen patients did not receive cytoreductive conditioning; some later received it.
- Graft-versus-host disease (GvHD) and immunological reconstitution were monitored.
Main Results:
- Eleven of fifteen patients are alive with stable T-cell functions.
- T-cell functions developed in eleven patients without significant GvHD.
- Two patients required cytoreductive conditioning for successful engraftment and reconstitution.
- Normal humoral immune functions developed in three patients; others required gamma globulin substitution.
Conclusions:
- T-cell-depleted, HLA-haplo-identical BMT can achieve immunological reconstitution in the majority of SCID patients without GvHD.
- Cytoreductive conditioning may be necessary for engraftment and humoral immune reconstitution in select SCID patients.
- This approach offers a viable therapeutic option for SCID, minimizing GvHD complications.
Abstract:
In 15 infants with severe combined immunodeficiency (SCID), immunological reconstitution was attempted by bone marrow transplantation (BMT) from HLA-haplo-identical parents. To prevent graft versus host disease (GvHD), marrow grafts were depleted of contaminating T-lymphocytes using lectin agglutination and rosette formation with sheep red blood cells. Thirteen patients received transplants without undergoing prior cytoreductive conditioning. Eleven of these developed donor-dependent T-cell functions, two failed to do this. One of these two as well as two further patients received cytoreductive treatment prior to repeat and to first transplants and in two, complete lymphohemopoietic reconstitution was observed. Of the 15 patients who received transplants, 11 are currently alive. Two recently treated patients remain in the hospital, nine are at home with stable T-cell functions. Normal humoral immune functions have developed upto now in three patients. In the others, gamma globulins are regularly substituted. Complications of acute or chronic GvHD were not observed with the exception of one case who developed transient GvHD of the skin. These results suggest that in a majority of patients with SCID, T-cell functions can develop without GvHD following haploidentical, T-cell-depleted BMT. Exceptional patients require preconditioning to allow donor cell engraftment, an approach that also appears to facilitate reconstitution of humoral immune functions.