Outcome of children with aplastic anemia treated with immunosuppressive therapy

Abstract

Background Immunosuppressive therapy (IST) is the alternative treatment in children with aplastic anemia (AA) who do not have an HLA‐matched sibling. The aim of this study is to evaluate the outcome of children with AA treated with IST. Methods We retrospectively reviewed the hospital records of children with AA from 1984 to 2004, treated at our institution with antithymocyte globulin (ATG), cyclosporine (CS), and short course of prednisone. Result Forty‐two patients were treated with IST (24 boys, 18 girls); of whom 26% received G‐CSF. The median age at diagnosis was 8.5 years. Sixty‐nine, 19, and 12% were diagnosed with severe, very severe, and moderate AA, respectively. Twenty‐one percent had hepatitis‐associated AA. Median follow‐up time was 53.3 months. Sixty‐two percent had complete response; 19% had partial response. Two patients relapsed and received a second course of ATG; both had a partial response. The actuarial 5 years survival rate was 67.5%. Two patients developed myelodysplastic syndrome (MDS); both received long‐term G‐CSF and had partial response after two courses of IST. Fifteen percent of survivors had significant hypertension which persisted after CS was discontinued. Conclusions This study shows promising response in children with AA treated with IST; however, the outcome was inferior to our institutional results with hematopoietic stem cell transplantation from a sibling donor. Hypertension and MDS are late complications. Longer follow‐up, larger cohorts, and prospective studies are warranted to evaluate late complications and risk factors. Pediatr Blood Cancer 2008;50:52–57. © 2007 Wiley‐Liss, Inc.

Pilot study using tacrolimus rather than cyclosporine plus antithymocyte globulin as an immunosuppressive therapy regimen option for severe aplastic anemia in adults

“…The present study of 37 SAA patients treated with IST showed CR and PR rates of greater than 75%, with a robust function with regard to both tacrolimus-and CsA-based therapies. Compared to the previously reported clonal transformation rates of approximately 10% for CsA-based IST [20,[22][23][24][25], no clonal transformation to PNH or MDS/AML was observed in either of our groups. A recent study on pediatric SAA reported that tacrolimus could be used as an alternative to cyclosporine in the maintenance phase of IST, with 88% PR; in this eight-case study, one case failed to response to IST-based therapy and subsequently underwent successful unrelated cord blood HSCT, and one patient showed PNH transformation, as detected using flow cytometry [28].…”

Editorials

“…They evaluated the efficacy of immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CSA) on 33 pediatric patients with acquired aplastic anemia in the Indian setting. Their results indicate that in India, with appropriate supportive care, pediatric aplastic anemia patients treated with IST can achieve response rates similar to North America and Europe, where the response rate is as high as 81% [2]. In addition, they confirm the experience of other authors, that ATG and CSA alone are the backbone of IST in treating childhood aplastic anemia, and that administration of G-CSF reduced infectious complications, but had no impact on survival or outcome [3].…”

“…The data yields other interesting trends: compared to the 42 pediatric patients treated with IST in Toronto by Pongtanakul, et al [2], although response rates were similar (88 vs 81%), there was a significant decrease in the percentage of patients with complete response (CR) (24% vs 62%) with an increase in partial response (PR) (64% vs 19%). This predominance of partial responders was seen also in another Indian series reported by Chandra, et al [5], who raised the question of effective cyclosporine administration, given the expense and uncertain quality in the open market.…”

“…The exact results of clinical effectiveness of amoxicillin in community acquired pneumonia in their set-up should have been mentioned, which has a bearing on the evolution of symptoms and signs. When the WHO recommendation is 3-5 days of antibiotic therapy for non severe pneumonia [2], unwarranted administration for 10 days can lead to related adverse events, escalation of cost and emergence of drug-resistance.…”

Management of acquired aplastic anemia in children

“…39 Response rates to IST in children are favorable, with survival ranging from 68% in one institution to 80% in another retrospective study at 10 years, with 89% survival if the analysis is confined to responders to IST. [40][41][42] There are data demonstrating the risk for malignant evolution over time with IST therapy, with rates of MDS/acute myelogenous leukemia ranging from 8 to 25%. 9,43 Modifications to the conventional IST regimen, including addition of danazol, mycophenolate mofetil, sirolimus or hematopoietic growth factors, have not significantly improved response or decreased relapse rates.…”