High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia

A nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group

Hiroyuki Takahashi, Tomoyuki Watanabe, Akitoshi Kinoshita, Yuki Yuza, Hiroshi Moritake, Kiminori Terui, Shotaro Iwamoto, Hideki Nakayama, Akira Shimada, Kazuko Kudo, Tomohiko Taki, Miharu Yabe, Hiromichi Matsushita, Yuka Yamashita, Kazutoshi Koike, Atsushi Ogawa, Yoshiyuki Kosaka, Daisuke Tomizawa, Takashi Taga, Akiko M. Saito & 5 others Keizo Horibe, Tatsutoshi Nakahata, Hayato Miyachi, Akio Tawa, Souichi Adachi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusAccepted/In press - 2016

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Acute Promyelocytic Leukemia
Anthracyclines
Disease-Free Survival
Lymphoma
Leukemia
Survival Rate
Prospective Studies
Pediatrics
Tretinoin
Confidence Intervals
Consolidation Chemotherapy
Therapeutics
Induction Chemotherapy
Intracranial Hemorrhages
Cytarabine
Complementary Therapies
Bone Marrow
Drug Therapy
Infection

Keywords

  • Acute promyelocytic leukaemia
  • Anthracyclines
  • Childhood leukemia
  • Clinical trial
  • Recombinant human soluble thrombomodulin

ASJC Scopus subject areas

  • Hematology

Cite this

High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia : A nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group. / Takahashi, Hiroyuki; Watanabe, Tomoyuki; Kinoshita, Akitoshi; Yuza, Yuki; Moritake, Hiroshi; Terui, Kiminori; Iwamoto, Shotaro; Nakayama, Hideki; Shimada, Akira; Kudo, Kazuko; Taki, Tomohiko; Yabe, Miharu; Matsushita, Hiromichi; Yamashita, Yuka; Koike, Kazutoshi; Ogawa, Atsushi; Kosaka, Yoshiyuki; Tomizawa, Daisuke; Taga, Takashi; Saito, Akiko M.; Horibe, Keizo; Nakahata, Tatsutoshi; Miyachi, Hayato; Tawa, Akio; Adachi, Souichi.

In: British Journal of Haematology, 2016.

Research output: Contribution to journalArticle

Takahashi, H, Watanabe, T, Kinoshita, A, Yuza, Y, Moritake, H, Terui, K, Iwamoto, S, Nakayama, H, Shimada, A, Kudo, K, Taki, T, Yabe, M, Matsushita, H, Yamashita, Y, Koike, K, Ogawa, A, Kosaka, Y, Tomizawa, D, Taga, T, Saito, AM, Horibe, K, Nakahata, T, Miyachi, H, Tawa, A & Adachi, S 2016, 'High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: A nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group', British Journal of Haematology. https://doi.org/10.1111/bjh.14068
Takahashi, Hiroyuki ; Watanabe, Tomoyuki ; Kinoshita, Akitoshi ; Yuza, Yuki ; Moritake, Hiroshi ; Terui, Kiminori ; Iwamoto, Shotaro ; Nakayama, Hideki ; Shimada, Akira ; Kudo, Kazuko ; Taki, Tomohiko ; Yabe, Miharu ; Matsushita, Hiromichi ; Yamashita, Yuka ; Koike, Kazutoshi ; Ogawa, Atsushi ; Kosaka, Yoshiyuki ; Tomizawa, Daisuke ; Taga, Takashi ; Saito, Akiko M. ; Horibe, Keizo ; Nakahata, Tatsutoshi ; Miyachi, Hayato ; Tawa, Akio ; Adachi, Souichi. / High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia : A nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group. In: British Journal of Haematology. 2016.
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abstract = "We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6{\%} [95{\%} confidence interval (CI): 68·6-91·8{\%}] and 90·7{\%} (95{\%} CI: 77·1-96·4{\%}), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3{\%} (95{\%} CI: 19·3-67·6{\%}) and 54·6{\%} (95{\%} CI: 22·9-78·0{\%}), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.",
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T2 - A nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group

AU - Takahashi, Hiroyuki

AU - Watanabe, Tomoyuki

AU - Kinoshita, Akitoshi

AU - Yuza, Yuki

AU - Moritake, Hiroshi

AU - Terui, Kiminori

AU - Iwamoto, Shotaro

AU - Nakayama, Hideki

AU - Shimada, Akira

AU - Kudo, Kazuko

AU - Taki, Tomohiko

AU - Yabe, Miharu

AU - Matsushita, Hiromichi

AU - Yamashita, Yuka

AU - Koike, Kazutoshi

AU - Ogawa, Atsushi

AU - Kosaka, Yoshiyuki

AU - Tomizawa, Daisuke

AU - Taga, Takashi

AU - Saito, Akiko M.

AU - Horibe, Keizo

AU - Nakahata, Tatsutoshi

AU - Miyachi, Hayato

AU - Tawa, Akio

AU - Adachi, Souichi

PY - 2016

Y1 - 2016

N2 - We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.

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KW - Acute promyelocytic leukaemia

KW - Anthracyclines

KW - Childhood leukemia

KW - Clinical trial

KW - Recombinant human soluble thrombomodulin

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