Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine.
Currently, the standard management of moderate aplastic anemia (MAA) has not been well described, although the superiority of the combination of antithymocyte globulin (ATG) and cyclosporine (CyA) over CyA alone has been demonstrated in terms of hematological responses and failure-free survival (FFS).



We adopted this therapeutic strategy and treated 95 children with MAA who were enrolled in two consecutive prospective studies between October 1992 and August 2009.



For these patients, the 6-month response rate was 54.7% (complete response, 13.7%; partial response, 41.1%). There were no statistically significant differences in the overall response rates between the transfusion-dependent (48.8%, n = 41) and transfusion-independent groups (59.3%, n = 54; P = 0.4). Treatment failure was defined as the requirement of salvage treatment, and was observed in 52 patients. The 10-year FFS was 44.0% (95% confidence interval [CI], 32.9%-54.6%). Of the 22 patients who underwent a second immunosuppressive therapy (IST), 12 responded. Forty patients underwent hematopoietic stem cell transplantation as second- or third-line therapy and three died of complications. Consequently, the 10-year overall survival rate was 96.0% (95% CI, 88.0%-98.7%) with a median follow-up period of 103 months (range, 29-221 months).



Although current guidelines recommend only observation for patients with transfusion-independent MAA, the results of our study justify early intervention with ATG and CyA in those patients. A prospective randomized trial is warranted to clarify the risks and benefits of early intervention with IST and observation alone until progression to severe AA in patients with MAA.
School of Medicine, Nihon University, Itabashi, Japan.|Graduate School of Medicine, Nagoya University, Japan.
Eri
E
Nishikawa
School of Medicine, Nihon University, Itabashi, Japan.
Hiroshi
H
Yagasaki
Graduate School of Medicine, Nagoya University, Japan.
Asahito
A
Hama
School of Medicine, Tokai University, Isehara, Japan.
Hiromasa
H
Yabe
School of Medicine, Toho University, Ohta, Japan.
Akira
A
Ohara
Hyogo Children's Hospital, Kobe, Japan.
Yoshiyuki
Y
Kosaka
School of Medicine, Fujita Health University, Aichi, Japan.
Kazuko
K
Kudo
Sapporo Hokuyu Hospital, Sapporo, Japan.
Ryoji
R
Kobayashi
Graduate School of Medicine, Yamaguchi University, Ube, Japan.
Shouichi
S
Ohga
School of Medicine, Jichi Medical University, Shimotsuke, Japan.
Akira
A
Morimoto
Shizuoka Children's Hospital, Shizuoka, Japan.
Ken-Ichiro
KI
Watanabe
Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Nao
N
Yoshida
Graduate School of Medicine, Nagoya University, Japan.
Hideki
H
Muramatsu
Graduate School of Medicine, Nagoya University, Japan.
Yoshiyuki
Y
Takahashi
Graduate School of Medicine, Nagoya University, Japan.
Seiji
S
Kojima
D000293:Adolescent; D000741:Anemia, Aplastic / Q000188:drug therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine
immunosuppressive therapy (IST); moderate aplastic anemia (MAA); pediatrics; transfusion dependent