Skip to main content
SpringerLink
Log in

Outcome of pediatric acute lymphoblastic leukemia with very late relapse: a retrospective analysis by the Tokyo Children’s Cancer Study Group (TCCSG)

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Relapse period is strongly associated with second relapse risk in relapsed acute lymphoblastic leukemia (ALL) in children. In this context, the treatment outcome of very late relapse should be better; however, data regarding very late relapse is limited. We retrospectively analyzed the outcomes of two consecutive Tokyo Children’s Cancer Study Group (TCCSG) ALL trials (1995–2004) with a focus on late relapse, which was divided into two categories: late relapse (6–24 months from the end of therapy, n = 48) and very late relapse (>24 months from the end of therapy, n = 57). Forty-three patients (29 late relapse and 14 very late relapse) received allogeneic hematopoietic stem cell transplantation (HSCT) at second remission. The event-free survival (EFS) probabilities of late relapse and very late relapse were 54.5 ± 7.3 and 64.8 ± 6.8 % at 7 years, respectively (P = 0.36), and were not significantly different. However, the second relapse incidence of late relapse (34.7 ± 7.1 %) was higher than that of very late relapse (15.5 ± 5.1 %, P = 0.03). The second relapse risk was low for very late relapse ALL, which suggests that these patients should be treated without allogeneic HSCT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Horibe K, Saito AM, Takimoto T, Tsuchida M, Manabe A, Shima M, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006–2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013;98:74–88.

    Article  PubMed  Google Scholar 

  2. Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A, et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011;118:2077–84.

    Article  CAS  PubMed  Google Scholar 

  3. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115:3206–14.

    Article  CAS  PubMed  Google Scholar 

  4. Vora A, Goulden N, Mitchell C, Hancock J, Hough R, Rowntree C, et al. Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2014;15:809–18.

    Article  PubMed  Google Scholar 

  5. Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14:199–209.

    Article  CAS  PubMed  Google Scholar 

  6. Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360:2730–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010;376:2009–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010;28:2339–47.

    Article  CAS  PubMed  Google Scholar 

  9. Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grumayer R, et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013;31:2736–42.

    Article  PubMed  Google Scholar 

  10. Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A, et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol. 2009;27:377–84.

    Article  PubMed  Google Scholar 

  11. Borgmann A, von Stackelberg A, Hartmann R, Ebell W, Klingebiel T, Peters C, et al. Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission: a matched-pair analysis. Blood. 2003;101:3835–9.

    Article  CAS  PubMed  Google Scholar 

  12. Bailey LC, Lange BJ, Rheingold SR, Bunin NJ. Bone-marrow relapse in paediatric acute lymphoblastic leukaemia. Lancet Oncol. 2008;9:873–83.

    Article  PubMed  Google Scholar 

  13. van den Berg H, Groot-Kruseman HA, Damen-Korbijn CM, Bont ES, Schouten-van Meeteren AY, Hoogerbrugge PM. Outcome after first relapse in children with acute lymphoblastic leukemia: a report based on the Dutch Childhood Oncology Group (DCOG) relapse all 98 protocol. Pediatr Blood Cancer. 2011;57:210–6.

    Article  PubMed  Google Scholar 

  14. Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14:e205–17.

    Article  PubMed  Google Scholar 

  15. Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children’s Oncology Group Study (corrected). J Clin Oncol. 2008;26:3971–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Buchanan GR, Rivera GK, Pollock BH, Boyett JM, Chauvenet AR, Wagner H, et al. Alternating drug pairs with or without periodic reinduction in children with acute lymphoblastic leukemia in second bone marrow remission: a Pediatric Oncology Group Study. Cancer. 2000;88:1166–74.

    Article  CAS  PubMed  Google Scholar 

  17. Rizzari C, Valsecchi MG, Arico M, Miniero R, Messina C, De Rossi G, et al. Outcome of very late relapse in children with acute lymphoblastic leukemia. Haematologica. 2004;89:427–34.

    PubMed  Google Scholar 

  18. Vora A, Frost L, Goodeve A, Wilson G, Ireland RM, Lilleyman J, et al. Late relapsing childhood lymphoblastic leukemia Blood. 1998;92:2334–7.

    CAS  Google Scholar 

  19. Chessells JM, Leiper AD, Richards SM. A second course of treatment for childhood acute lymphoblastic leukaemia: long-term follow-up is needed to assess results. Br J Haematol. 1994;86:48–54.

    Article  CAS  PubMed  Google Scholar 

  20. Igarashi S, Manabe A, Ohara A, Kumagai M, Saito T, Okimoto Y, et al. No advantage of dexamethasone over prednisolone for the outcome of standard- and intermediate-risk childhood acute lymphoblastic leukemia in the Tokyo Children’s Cancer Study Group L95-14 protocol. J Clin Oncol. 2005;23:6489–98.

    Article  CAS  PubMed  Google Scholar 

  21. Manabe A, Ohara A, Hasegawa D, Koh K, Saito T, Kiyokawa N, et al. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group Study L99-15. Haematologica. 2008;93:1155–60.

    Article  CAS  PubMed  Google Scholar 

  22. Hasegawa D, Manabe A, Ohara A, Kikuchi A, Koh K, Kiyokawa N, et al. The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99-15 study. Pediatr Blood Cancer. 2012;58:23–30.

    Article  PubMed  Google Scholar 

  23. Kato M, Koh K, Manabe A, Saito T, Hasegawa D, Isoyama K, et al. No impact of enhanced early intensification with intermediate-risk pediatric acute lymphoblastic leukemia: results of randomized trial TCCSG study L99-15. Br J Haematol. 2014;164:376–83.

    Article  CAS  PubMed  Google Scholar 

  24. Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, et al. A revised definition for cure of childhood acute lymphoblastic leukemia. Leukemia. 2014

  25. Ford AM, Fasching K, Panzer-Grumayer ER, Koenig M, Haas OA. & Greaves MF Origins of “late” relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes. Blood. 2001;98:558–64.

    Article  CAS  PubMed  Google Scholar 

  26. Konrad M, Metzler M, Panzer S, Ostreicher I, Peham M, Repp R, et al. Late relapses evolve from slow-responding subclones in t(12;21)-positive acute lymphoblastic leukemia: evidence for the persistence of a preleukemic clone. Blood. 2003;101:3635–40.

    Article  CAS  PubMed  Google Scholar 

  27. Inukai T, Yokota S, Okamoto T, Nemoto A, Akahane K, Takahashi K, et al. Clonotypic analysis of acute lymphoblastic leukemia with a double TEL-AML1 fusion at onset and relapse. Leukemia. 2006;20:363–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Kaori Itagaki for preparing and refining the protocol data for ALL in the TCCSG. We also thank the pediatricians and nurses who participated in the treatment and follow-up of the patients in this study.

Conflict of interest

All authors had no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Pediatrics, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Motohiro Kato

  2. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo, Japan

    Motohiro Kato

  3. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Atsushi Manabe

  4. Laboratory of Clinical, Epidemiological and Health Services Research, Clinical Research Center, National Hospital Organization Nagoya Medical Cente, Nagoya, Japan

    Akiko M. Saito

  5. Department of Hematology/Oncology, Saitama Children’s Medical Centre, Saitama, Japan

    Katsuyoshi Koh

  6. Department of Pediatrics, University of Yamanashi, Yamanashi, Japan

    Takeshi Inukai

  7. Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan

    Chitose Ogawa

  8. Division of Hemato-oncology/Regenerative Medicine, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroyuki Goto

  9. Department of Hematology/Oncology, Ibaraki Children’s Hospital, Ibaraki, Japan

    Masahiro Tsuchida

  10. Department of Pediatrics, Toho University, Tokyo, Japan

    Akira Ohara

Authors
  1. Motohiro Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atsushi Manabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akiko M. Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuyoshi Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takeshi Inukai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chitose Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroyuki Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masahiro Tsuchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akira Ohara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Motohiro Kato.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kato, M., Manabe, A., Saito, A.M. et al. Outcome of pediatric acute lymphoblastic leukemia with very late relapse: a retrospective analysis by the Tokyo Children’s Cancer Study Group (TCCSG). Int J Hematol 101, 52–57 (2015). https://doi.org/10.1007/s12185-014-1710-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-014-1710-z

Keywords

Search

Navigation