Immunosuppressive Therapy in Children with Refractory Anemia: Results of Japanese Childhood MDS Study Group Trial (MDS99).

Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder and uncommon in childhood. Especially, refractory anemia (RA), which is a subgroup of MDS without an increased number of blasts, is quite rare in this age group. Although hematopoietic stem cell transplantation (HSCT) is thought to be a curative therapy for pediatric MDS, it may cause severe complications and mortality. Several reports have shown encouraging results with immunosuppressive therapy (IST) in adult patients with RA. We report the outcome of 12 children with RA enrolled on a prospective multicenter trial conducted by Japanese childhood MDS study group. In this study, a child who was suspected of having RA required repetitive bone marrow aspiration at 6–8 weeks intervals. If the disease was stable and blood transfusion was not urgent, the patient could be monitored closely without any therapy. If physicians decided to start therapy due to progression of cytopenia, the patient received IST consisting antithymocyte globulin (ATG), cyclosporine (CyA) and methylprednisolone (mPSL). Of the 12 children, 9 received IST (IST group), 2 were followed without treatment (observation group) and one underwent HSCT without IST. Seven children showed hematological response in the IST group, and a response rate was 77.8%. Of note, 1 patient with monosomy 7 showed complete cytogenetic response after IST and remained in remission. One patient became refractory to IST after relapse and underwent bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) 1-antigen mismatch relative, and she is alive without disease on 351 days after HSCT. One patient received BMT from an HLA-matched unrelated donor without IST because he had monosomy 7, but he relapsed and died from disease progression. Neither of 2 patients in the observation group experienced disease progression. There were 8 children who showed chromosomal abnormalities, including monosomy 7 and trisomy 8, 7 of whom received IST and 6 children showed hematological response. No severe adverse events related to IST were reported in this study. Eleven of the 12 patients are alive after a median follow-up of 1,319 days. The probability of survival at 5 years was 88.9%, which was superior to our previous retrospective analysis of children with RA. We conclude that IST for children with RA seems an effective modality and warrants an international clinical trial.