Natural History of Transfusion-Independent Non-Severe Aplastic Anemia in Children.

The known clinical courses of non-severe aplastic anemia (NSAA) in children are spontaneous resolution, persistent NSAA, or progression to severe aplastic anemia (SAA). A few published reports have indicated the outcome of transfusion-independent NSAA. We performed a retrospective analysis of transfusion-independent NSAA to evaluate the incidence and time of progression to transfusion-dependent NSAA or SAA. We reviewed the records of 70 children with acquired aplastic anemia referred to Nagoya University Hospital between September, 1986 and August, 2006. Transfusion-independent NSAA was defined as hypocellular marrow and at least 2 cytopenias that persisted for several weeks, without meeting the criteria for SAA (neutrophil count less than 500/μl, a platelet count less than 20,000/μl, and an absolute reticulocyte count less than 20,000/μl). We included only children (aged less than 18 years) with transfusion-independent NSAA at diagnosis who were treated with supportive care alone. The median ages of the 23 patients who met the criteria were 7.7 years (range, 3.0–15.2 y) and 15 were female. The etiology of the aplastic anemia was unknown in all patients. At diagnosis, median neutrophil, platelet and reticulocyte counts were 1,040/μl (range, 380–3,200/μl), 41,000/μl (range, 20,000–126,000/μl) and 63,000/μl (range, 10,000–120,000/μl), respectively. Of 22 patients for whom chromosomal data were available, none had chromosomal abnormalities at diagnosis. Patients were followed for a median of 89 months (range, 11–198 months). Transfusion-independent NSAA persisted in 10 (43%) patients at a median of 30 months (range, 11–117 months) after diagnosis. On the other hand, 13 (57%) progressed to transfusion-dependent NSAA or SAA at a median of 53 months (range, 9–175 months) after diagnosis and required some treatment. Of these 13 patients, 4 received androgens, 2 received high-dose methylprednisolone, 1 received immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine, and 4 underwent hematopoietic stem cell transplantation (HSCT) from HLA-matched siblings. The Kaplan-Meier estimate for progression-free survival was 64%±11% at 5 years and 25%±12% at 10 years, respectively. None of the patients treated with supportive care alone had hematological improvement. None developed paroxysmal nocturnal hemoglobinuria or myelodysplastic syndrome, and all patients are currently alive. In conclusion, NSAA did not spontaneously resolve in any of the 23 patients and the incidence of disease progression was high. Whether early intervention with IST or supportive care alone is preferable should be compared.