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Nelarabine-containing salvage therapy and conditioning regimen in transplants for pediatric T-cell acute lymphoblastic leukemia and lymphoma

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Abstract

Therapy for relapsed or refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in children is challenging, and new treatment methods are needed. We retrospectively analyzed eight patients with r/r T-ALL (five patients) and T-LBL (three patients) who were treated with nelarabine (NEL) plus etoposide, cyclophosphamide, and intrathecal therapy, administered 3 days apart. Five patients achieved a complete response, and the other three achieved a partial response (PR). All patients underwent hematopoietic stem cell transplantation (HSCT) after two cycles of treatment, except for one patient who received one cycle. Three patients who had previously received HSCT were treated with reduced-intensity conditioning regimens, including fludarabine, melphalan, and NEL; one survived for over 5 years after the second HSCT. Grade 2 neuropathy occurred in one patient, but other severe toxicities commonly associated with NEL were not observed during NEL administration in combination with chemotherapy. The 2-year overall survival and event-free survival rates were 60.0% and 36.5%, respectively. The addition of NEL to reinduction chemotherapy was useful in achieving remission and did not lead to excessive toxicity. In addition, a conditioning regimen, including NEL, appeared to be effective in patients who had previously undergone HSCT.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541–52.

    Article  CAS  PubMed  Google Scholar 

  2. Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. Br J Haematol. 2013;162(5):606–20.

    Article  PubMed  Google Scholar 

  3. Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol. 2015;33:2938–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Teachey DT, O’Connor D. How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children. Blood. 2020;135(3):159–66.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. 2012;30:1663–9.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, et al. Children’s oncology group AALL0434: a phase III randomized clinical trial testing nelarabine in lymphoblastic leukemia. J Clin Oncol. 2020;38:3282–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Burkhardt B, Mueller S, Khanam T, Perkins SL. Current status and future directions of T-lymphoblastic lymphoma in children and adolescents. Br J Haematol. 2016;173:554–9.

    Article  Google Scholar 

  8. Burkhardt B, Reiter A, Landmann E, Lang P, Lassay L, Dickerhoff R, et al. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the Berlin–Frankfurt–Muenster group. Ann Hematol. 2009;27:3363–9.

    Google Scholar 

  9. Eckert C, Hagedorn N, Sramkova L, Mann G, Panzer-Grümayer R, Peters C, et al. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment. Leukemia. 2015;29:1648–55.

    Article  CAS  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. 2008;27:377–84.

    Article  PubMed  Google Scholar 

  11. Ullman B, Martin DW. Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts. J Clin Invest. 1984;74(3):951–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shewach DS, Daddona PE, Ashcraft E, Mitchell BS. Metabolism and selective cytotoxicity of 9-beta-D-arabinofuranosylguanine in human lymphoblasts. Cancer Res. 1985;45(3):1008–14.

    CAS  PubMed  Google Scholar 

  13. Rodriguez CO Jr, Stellrecht CM, Gandhi V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood. 2003;102:1842–8.

    Article  CAS  PubMed  Google Scholar 

  14. Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the children’s oncology group. J Clin Oncol. 2005;23:3376–82.

    Article  CAS  PubMed  Google Scholar 

  15. Gandhi V, Tam C, O’Brien S, Jewell RC, Rodriguez CO Jr, Lerner S, et al. Phase I trial of nelarabine in indolent leukemias. J Clin Oncol. 2008;26:1098–105.

    Article  CAS  PubMed  Google Scholar 

  16. Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, et al. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017;179:284–93.

    Article  CAS  PubMed  Google Scholar 

  17. Candoni A, Lazzarotto D, Ferrara F, Curti A, Lussana F, Papayannidis C, et al. Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol. 2020;95:1466–72.

    Article  CAS  PubMed  Google Scholar 

  18. Commander LA, Seif AE, Insogna IG, Rheingold SR. Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma. Br J Haematol. 2010;150:345–51.

    Article  CAS  PubMed  Google Scholar 

  19. Luskin MR, Ganetsky A, Landsburg DJ, Loren DJ, Porter D, Nasta SD, et al. Nelarabine, cyclophosphamide and etoposide for adults with relapsed T-cell acute lymphoblastic leukaemia and lymphoma. Br J Haematol. 2016;174(2):332–4.

    Article  PubMed  Google Scholar 

  20. Kumamoto T, Goto H, Ogawa C, Hori T, Deguchi T, Araki T, et al. FLEND (nelarabine, fludarabine, and etoposide) for relapsed T-cell acute lymphoblastic leukemia in children: a report from Japan children’s cancer group. Int J Hematol. 2020;112:720–4.

    Article  CAS  PubMed  Google Scholar 

  21. Whitlock JA, Malvar J, Dalla-Pozza L, Goldberg JM, Silverman LB, Ziegler DS, et al. Nelarabine, etoposide, and cyclophosphamide in relapsed pediatric T-acute lymphoblastic leukemia and T-lymphoblastic lymphoma (study T2008–002 NECTAR). Pediatr Blood Cancer. 2022;69: e29901.

    Article  CAS  PubMed  Google Scholar 

  22. Abaza Y, Kantarjian HM, Faderl S, Jabbour E, Jain N, Thomas D, et al. Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma. Am J Hematol. 2018;93:91–9.

    Article  CAS  PubMed  Google Scholar 

  23. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  PubMed  Google Scholar 

  25. Morita K, Jain N, Kantarjian H, Taahashi K, Fang H, Konopleva M, et al. Outcome of T-cell acute lymphoblastic leukemia/lymphoma: Focus on near-ETP phenotype and differential impact of nelarabine. Am J Hematol. 2021;96:589–98.

    Article  CAS  PubMed  Google Scholar 

  26. Davies SM, Ramsay NK, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY, et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol. 2000;18(2):340–7.

    Article  CAS  PubMed  Google Scholar 

  27. Kato M, Ishida H, Koh K, Inagaki J, Kato K, Goto H, et al. Comparison of chemotherapeutic agents as a myeloablative conditioning with total body irradiation for pediatric acute lymphoblastic leukemia: a study from the pediatric ALL working group of the Japan society for hematopoietic cell transplantation. Pediatr Blood Cancer. 2015;62:1844–50.

    Article  CAS  PubMed  Google Scholar 

  28. Lambe CU, Averett DR, Paff MT, Reardon JE, Wilson JG, Krenitsky TA. 2-Amino-6-methoxypurine arabinoside: an agent for T-cell malignancies. Cancer Res. 1995;55(15):3352–6.

    CAS  PubMed  Google Scholar 

  29. Gandhi V, Plunkett W, Rodriguez CO Jr, Nowak BJ, Du M, Kisor M, et al. Compound GW506U78 in refractory hematologic malignancies: relationship between cellular pharmacokinetics and clinical response. J Clin Oncol. 1998;16:3607–15.

    Article  CAS  PubMed  Google Scholar 

  30. Gandhi V, Plunkett W, Weller S, Du M, Ayres M, Rodriguez CO Jr, et al. Evaluation of the combination of nelarabine and fludarabine in leukemias: clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells. J Clin Oncol. 2001;19:2142–52.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are indebted to the patient’s families, nursing, and medical staff in our hospital. We would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Masato Yanagi, Makiko Mori, Mamoru Honda, Yuichi Mitani, Masafumi Seki, Kohei Fukuoka, Koichi Oshima, Yuki Arakawa & Katsuyoshi Koh

  2. Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo, 003-0006, Japan

    Masato Yanagi

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  1. Masato Yanagi
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  2. Makiko Mori
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Correspondence to Masato Yanagi.

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Yanagi, M., Mori, M., Honda, M. et al. Nelarabine-containing salvage therapy and conditioning regimen in transplants for pediatric T-cell acute lymphoblastic leukemia and lymphoma. Int J Hematol 119, 327–333 (2024). https://doi.org/10.1007/s12185-023-03701-z

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  • DOI: https://doi.org/10.1007/s12185-023-03701-z

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