Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in children and young adults

Abstract

Alternative donor bone marrow transplantation (BMT) to treat severe aplastic anaemia (SAA) in children and young adults has been complicated by high rates of graft rejection and severe graft-versus-host disease (GVHD). We hypothesized that increased immunosuppression combined with T-cell depletion of the marrow graft would enable successful use of unrelated donor BMT in this disease. Preconditioning consisted of cytosine arabinoside, cyclophosphamide, and total body irradiation (TBI). T-cell depletion was with the anti-CD3 antibody T10B9. GVHD prophylaxis consisted of cyclosporine A. 28 previously transfused patients were transplanted. Nine donor/recipient pairs were HLA matched. As of 1 January 1996, 15/28 (54%) patients are alive, transfusion independent and well with a range of follow-up of 13 months to 8 years (median 2.75 years). Fatalities include all three patients with nonengraftment and all three patients with grade III/IV GVHD. Other fatalities were due to infections or therapy-related toxicity. The incidence >or= grade II acute GVHD was 28%. These data show that in children with SAA who have failed immunosuppression, unrelated donor BMT offers a reasonable hope of long-term survival.

Decision-Making and Problem Solving

“…10,15,23,26 DNA-based HLA-typing was performed for all participants in 5 published studies, 16,20,28,29,31 and for the majority of participants in 5 other studies. 15 10,17,20,21,23,25,[27][28][29][30][31][32] Reactivation of disease caused by cytomegalovirus and Epstein-Barr virus was observed in 3 studies. 23,31,32 In the controlled trial, 205 children and young people under 18 years of age with SAA were enrolled, 26 of whom 198 were treated with IST.…”

“…A median of 32 patients (range 11-349, total 1,645) were investigated in the total study population of 14 studies 11,[15][16][17][21][22][23][25][26][27][28][29]31,32 and in 8 relevant subgroups of 4 other studies. 10,20,24,30 The patients' median age in the individual studies was between eight and 27 years and the ratio of males : females ranged from a male (30 : 10) to a female preponderance (11 : 20).…”

“…15,16,20,24 A consecutive enrolment was stated in 3 23,25,27 of 13 retrospective case series. 10,11,17,[21][22][23]25,[27][28][29][30][31][32] Transplantations were performed between 1981 and 2006.…”

Unrelated peripheral blood stem cell transplantation with ‘megadoses’ of purified CD34+ cells in three children with refractory severe aplastic anemia

“…The results of mismatched family donor or matched unrelated bone marrow transplantations in patients failing such therapies, however, are not promising even though attempts have been made to overcome the risk of graft rejection as well as of GVHD by increasing the dose of the conditioning regimens and by reducing the number of transplanted T lymphocytes, respectively. 1,11 Recently an encouraging approach to prevent graft rejection has been reported by the use of 'megadose' stem cell transplants, assuming that the use of megadoses of CD34 + cells might abrogate resistance to engraftment and overcome even major HLA barriers in the unrelated donor setting. [12][13][14][15][16] High purification of CD34 + cells provides sufficient T cell depletion and therefore combines the advantage of high numbers of unrelated peripheral blood stem cells with a tolerable incidence of GVHD.…”

“…However, it is limited by a high risk of graft rejection and graft-versus-host disease (GVHD). [1][2][3][4][5] To overcome these problems, megadoses of unrelated highly purified peripheral CD34 + cells were used in this study. Magnetic cell sorting (MACS) was performed to purify the peripheral blood mononuclear cells with adequate recovery of CD34 + cells.…”