Immunosuppressive Therapy Response Research Articles

Successful treatment of severe aplastic anemia in children using standardized immunosuppressive therapy with antithymocyte globulin and cyclosporine A.

Given the heterogeneity of published data in US children, we sought to evaluate outcomes of a standardized immunosuppressive therapy (IST) regimen for severe aplastic anemia (SAA) at The Children's Hospital (Denver, CO). We retrospectively analyzed the records of 16 children diagnosed from 1990 to 2003 and treated by IST, among whom 14 received the standardized regimen of antithymocyte globulin (ATG) and cyclosporine A (CsA). Serial hematologic parameters, complications, transfusion requirements, and time to response were assessed. One child who died from a pre-existing Aspergillus infection prior to expected IST response was excluded from the analysis. Overall (transfusion-independent) response to IST was 100% (13/13), without any relapses or clinically evident leukemic/myelodysplastic transformations after a median follow-up time of 4.4 years (range: 10 months-13.3 years). This report documents excellent outcome using combination ATG and CsA IST for pediatric SAA.

Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group.

Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.