International Journal of Hematology

, Volume 107, Issue 2, pp 244–250 | Cite as

Prognostic impact of minimal disseminated disease and immune response to NPM-ALK in Japanese children with ALK-positive anaplastic large cell lymphoma

  • Yuka Iijima-Yamashita
  • Tetsuya Mori
  • Atsuko Nakazawa
  • Reiji Fukano
  • Tetsuya Takimoto
  • Masahito Tsurusawa
  • Ryoji Kobayashi
  • Keizo Horibe
Original Article


The prognostic impact of minimal disseminated disease (MDD) and anti-anaplastic lymphoma kinase (ALK) antibody titer in children with ALK-positive anaplastic large cell lymphoma (ALCL) was reported by an Italian/German group. Here, we examine their prognostic value in Japanese children with ALK-positive ALCL. We evaluated nucleophosmin (NPM)-ALK transcripts in 60 patients at diagnosis by RT-PCR and real-time PCR (qPCR). The antibody titer was assessed in 35 patients. Fifty-two percent were MDD positive by RT-PCR and 37% had more than 10 copies of NPM-ALK per 104 copies of ABL (10NCNs) by qPCR. Fifty-one percent of 35 patients had high antibody titer (> 1/750). Progression-free survival (PFS) of the patients with > 10 NCNs or low antibody titers was significantly poorer than that of patients with ≤ 10 NCNs or high antibody titers (> 1/750) (P = 0.016, 0.029), respectively, although we observed no difference in PFS associated with positive MDD on RT-PCR. On stratification using a combination of MDD and antibody titer, PFS for patients with > 10 NCNs and low antibody titer was extremely low (30.0%). Combined evaluation of MDD and anti-ALK antibody titer at diagnosis may thus be valuable for stratification of treatment for childhood ALCL.


ALCL Children MDD Anti-ALK antibody 



This work was supported by Grants for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan; H14-Koka(Gan)-031, H15-Koka(Gan)-024, H16-GanRinsho-004, H17-GanRinsho-004, H20-GanRinsho-Ippan-017, H23-GanRinsho-Ippan-014. We thank Drs. Angelo Rosolen, Lala Mussolin and Christine Damm-Welk for teaching procedures and providing the plasmid pcDNA3 NPM-ALK and Miho Yamada for helping with sample preparing. We also would like to thank all of the children, their parents and clinicians for participating in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they had no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 22 kb)
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Supplementary material 2 (DOCX 29 kb)
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Supplementary material 3 (DOCX 26 kb)
12185_2017_2338_MOESM4_ESM.pptx (67 kb)
Supplementary Figure S1 Kaplan–Meier curves for Overall Survival of patients according to MDD status in the bone marrow and/or peripheral blood (A) by RT-PCR and (B) by qPCR. NCN, normalized copy number; SE, standard error. (PPTX 67 kb)


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Department of Clinical Trials and Research, Clinical Research CenterNational Hospital Organization Nagoya Medical CenterNagoyaJapan
  2. 2.Department of PediatricsSt. Marianna University School of MedicineKawasakiJapan
  3. 3.Department of Clinical ResearchSaitama Children’s Medical CenterSaitamaJapan
  4. 4.Department of PediatricsNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
  5. 5.National Center for Child Health and DevelopmentTokyoJapan
  6. 6.Aichi Medical UniversityNagakuteJapan
  7. 7.Department of Hematology/Oncology for Children and AdolescentsSapporo Hokuyu HospitalSapporoJapan

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