Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine

Eri Nishikawa, Hiroshi Yagasaki, Asahito Hama, Hiromasa Yabe, Akira Ohara, Yoshiyuki Kosaka, Kazuko Kudo, Ryoji Kobayashi, Shoichi Ohga, Akira Morimoto, Ken Ichiro Watanabe, Nao Yoshida, Hideki Muramatsu, Yoshiyuki Takahashi, Seiji Kojima

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: 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). Procedure: 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. Results: 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). Conclusions: 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.

Original languageEnglish
Article numbere26305
JournalPediatric Blood and Cancer
Volume64
Issue number5
DOIs
Publication statusPublished - May 1 2017

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Antilymphocyte Serum
Aplastic Anemia
Cyclosporine
Horses
Immunosuppressive Agents
Observation
Confidence Intervals
Salvage Therapy
Survival
Hematopoietic Stem Cell Transplantation
Therapeutics
Treatment Failure
Survival Rate
Prospective Studies
Guidelines

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine. / Nishikawa, Eri; Yagasaki, Hiroshi; Hama, Asahito; Yabe, Hiromasa; Ohara, Akira; Kosaka, Yoshiyuki; Kudo, Kazuko; Kobayashi, Ryoji; Ohga, Shoichi; Morimoto, Akira; Watanabe, Ken Ichiro; Yoshida, Nao; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kojima, Seiji.

In: Pediatric Blood and Cancer, Vol. 64, No. 5, e26305, 01.05.2017.

Research output: Contribution to journalArticle

Nishikawa, E, Yagasaki, H, Hama, A, Yabe, H, Ohara, A, Kosaka, Y, Kudo, K, Kobayashi, R, Ohga, S, Morimoto, A, Watanabe, KI, Yoshida, N, Muramatsu, H, Takahashi, Y & Kojima, S 2017, 'Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine', Pediatric Blood and Cancer, vol. 64, no. 5, e26305. https://doi.org/10.1002/pbc.26305
Nishikawa, Eri ; Yagasaki, Hiroshi ; Hama, Asahito ; Yabe, Hiromasa ; Ohara, Akira ; Kosaka, Yoshiyuki ; Kudo, Kazuko ; Kobayashi, Ryoji ; Ohga, Shoichi ; Morimoto, Akira ; Watanabe, Ken Ichiro ; Yoshida, Nao ; Muramatsu, Hideki ; Takahashi, Yoshiyuki ; Kojima, Seiji. / Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine. In: Pediatric Blood and Cancer. 2017 ; Vol. 64, No. 5.
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abstract = "Background: 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). Procedure: 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. Results: 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). Conclusions: 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.",
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T1 - Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine

AU - Nishikawa, Eri

AU - Yagasaki, Hiroshi

AU - Hama, Asahito

AU - Yabe, Hiromasa

AU - Ohara, Akira

AU - Kosaka, Yoshiyuki

AU - Kudo, Kazuko

AU - Kobayashi, Ryoji

AU - Ohga, Shoichi

AU - Morimoto, Akira

AU - Watanabe, Ken Ichiro

AU - Yoshida, Nao

AU - Muramatsu, Hideki

AU - Takahashi, Yoshiyuki

AU - Kojima, Seiji

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Background: 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). Procedure: 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. Results: 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). Conclusions: 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.

AB - Background: 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). Procedure: 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. Results: 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). Conclusions: 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.

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