Success of allogeneic marrow transplantation for children with severe aplastic anaemia

Abstract

Allogeneic marrow transplantation offers curative therapy for children with severe aplastic anaemia (SAA). We report the outcomes of 148 children with SAA who received human leucocyte antigen (HLA)-matched related marrow grafts between 1971 and 2010. Patients were divided into three groups, reflecting changes in conditioning and graft-versus-host disease (GVHD) prophylaxis regimens that occurred over time. Patients in Group 1 were conditioned with cyclophosphamide (CY; 200 mg/kg) followed by 'long' (102 d) methotrexate (MTX). Patients in Groups 2 and 3 received CY alone (Group 2) or combined with anti-thymocyte globulin (Group 3) followed by 'short' (days 1, 3, 6, and 11) MTX and ciclosporin (until day 180). With a median follow-up of 25 years, the 5-year survivals were 66%, 95%, and 100% for Groups 1, 2, and 3, respectively (overall P < 0·0001). The 3-year estimates of graft rejection were 22%, 32%, and 7%, respectively. The probabilities of grades III-IV acute and 2-year chronic GVHD were 15%, 0%, and 3%, and 21%, 21%, and 10%, respectively. Advances in preparative and GVHD prophylaxis regimens, and supportive care during the past 40 years have led to improved outcomes for children with SAA. These results confirm the use of allogeneic marrow transplantation for children with SAA who have HLA-matched related donors.

© 2012 Blackwell Publishing Ltd.

Figures

Fig 1

Incidence of (A) graft rejection according to conditioning regimen and graft-versus-host disease (GVHD) prophylaxis over time in 148 children with severe aplastic anaemia (SAA) and (B) survival following second marrow transplantation for graft rejection according to the conditioning regimen and GVHD prophylaxis over time in 24 patients with SAA. ATG=anti-thymocyte globulin; CSP=ciclosporin; CY = cyclophosphamide; MTX=methotrexate.

Fig 2

Cumulative incidence of (A) Grade II acute graft-versus-host disease (GVHD) (B) Grade III–IV acute GVHD (C) and chronic GVHD in 148 children with severe aplastic anaemia. ATG=anti-thymocyte globulin; CSP=ciclosporin; CY = cyclophosphamide; MTX=methotrexate.

Fig 3

Survival (upper curves) and prevalence of chronic graft-versus-host disease (lower curves) among patients in (A) Group 1 (CY, MTX n=98) (B) Group 2 (CY, MTX + CSP n= 19) and (C) Group 3 (CY/ATG, MTX + CSP n=31) in 148 children with severe aplastic anaemia. ATG=anti-thymocyte globulin; CSP=ciclosporin; CY = cyclophosphamide; MTX=methotrexate.

Fig 4

Cumulative incidence of post-transplant cancer and cancer-related mortality in 148 children with severe aplastic anaemia.

Fig 5

Overall survival according to the conditioning regimen and graft-versus-host disease prophylaxis used in 148 children with severe aplastic anaemia. ATG=anti-thymocyte globulin; CSP=ciclosporin; CY = cyclophosphamide; MTX=methotrexate.