Improved survival in severe acquired aplastic anemia of childhood

Abstract

Summary:Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twentysix patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group. Bone Marrow Transplantation (2000) 26, 1149-1156.

Late effects among pediatric patients followed for nearly 4 decades after transplantation for severe aplastic anemia

“…2,3 Long-term survival of approximately 85%-100% has been observed for younger patients after BM transplantation from HLA-identical siblings after a preparative regimen with cyclophosphamide and antithymocyte globulin (CY ϩ ATG) followed by posttransplantation immunosuppression with methotrexate and cyclosporine (MTX ϩ CSP). 2,[4][5][6] As can be seen in Burroughs et al's report, 7 5-year survival after 1981 is 95%-100% for children who underwent transplantation at Fred Hutchinson Cancer Research Center (FHCRC).…”

First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

“…Of 3,085 retrieved publications, 358 full-text papers were obtained for further assessment and 26 non-randomized controlled clinical trials were identified that met the inclusion criteria and were included in the present study [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56]. We did not identify any RCTs.…”

“…Patients were recruited between 1970 and 2002 in 24 studies, whereas in 2 studies, year of treatment was not reported. In 13 studies [31], [34], [35], [39], [41], [42], [43], [44], [45], [46], [47], [49], [54], disease severity (SAA or VSAA) or first-line treatment was clearly classified for all patients. The proportion of patients with moderate aplastic anemia, unknown disease severity, or second-line treatment was less than 20% in 6 studies [32], [36], [38], [40], [50], [52] and was 20% or more in 7 studies [33], [37], [48], [51], [53], [55], [56].…”

“…We included 19 studies (4,855 patients) [31], [32], [33], [35], [37], [38], [39], [40], [42], [43], [45], [46], [47], [48], [49], [50], [51], [54], [55] in a meta-analysis on overall survival, which provided summary statistics required for estimating the hazard ratio. The pooled hazard ratio was statistically not significant and was characterized by a considerable heterogeneity indicated by an I 2 value of 75% (Figure 2).…”

Aplastic anaemia in childhood. Description of two cases and review of the literature

“…Immunosuppressive therapy using the combination of antithymocyte globulin (ATG), cyclosporin and methyprednisolone is indicated for other children who have no HLA compatible sibling [25,26]. Overall survival at 5 years is estimated at about 80%, but the eventfree survival rate is lower as a result of non response or relapse.…”