Skip to main content
SpringerLink
Log in

Cord blood transplantation with a reduced-intensity conditioning regimen using fludarabine and melphalan for adult T-cell leukemia/lymphoma

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

A Correction to this article was published on 17 March 2021

This article has been updated

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma with a poor prognosis when treated with chemotherapy alone; therefore, allogeneic stem cell transplantation is a consideration. We attempted cord blood transplantation (CBT) using a reduced-intensity conditioning regimen without total body irradiation (non-TBI-RIC) to allow for the best possible timing of transplantation and improve survival outcomes, particularly in older patients. Forty-eight patients (27 male, 21 female) underwent CBT using fludarabine (Flu) 125 mg/m2 and melphalan (Mel) 140 mg/m2 as pre-transplant conditioning. The median age was 32 years (range 44–72), and 21 patients were in complete remission (CR) at the time of CBT. The median duration to neutrophil engraftment (NE) was 19.5 days (range 15–50), with a cumulative incidence of NE of 86.7% at day 50 after CBT. The 1- and 3-year overall survival (OS) rates were 40.4% and 37.7%, respectively. The 3-year OS rate in CR patients was 60.8%, compared with 18.8% in non-CR patients. In ATLL patients, CBT with non-TBI-RIC using Flu/Mel is a promising treatment strategy.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Change history

References

  1. Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult t-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007;25:5458–64.

    Article  CAS  PubMed  Google Scholar 

  2. Bazarbachi A, Plumelle Y, Ramos JC, Tortevoye P, Otrock Z, Taylor G, et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol. 2010;28:4177–83.

    Article  CAS  PubMed  Google Scholar 

  3. Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol. 2012;30:1635–40.

    Article  CAS  PubMed  Google Scholar 

  4. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group. Br J Haematol. 1991;79:428–37.

    Article  CAS  PubMed  Google Scholar 

  5. Nosaka K, Iwanaga M, Imaizumi Y, Ishitsuka K, Ishizawa K, Ishida Y, et al. Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010–2011: a nationwide survey. Cancer Sci. 2017;108:2478–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Utsunomiya A, Miyazaki Y, Takatsuka Y, Hanada S, Uozumi K, Yashiki S, et al. Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27:15–20.

    Article  CAS  PubMed  Google Scholar 

  7. Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood. 2010;116:1369–76.

    Article  CAS  PubMed  Google Scholar 

  8. Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. Blood. 2012;120:1734–41.

    Article  CAS  PubMed  Google Scholar 

  9. Bazarbachi A, Cwynarski K, Boumendil A, Finel H, Fields P, Raj K, et al. Outcome of patients with HTLV-1-associated adult T-cell leukemia/lymphoma after SCT: a retrospective study by the EBMT LWP. Bone Marrow Transplant. 2014;49:1266–8.

    Article  CAS  PubMed  Google Scholar 

  10. Kato K, Choi I, Wake A, Uike N, Taniguchi S, Moriuchi Y, et al. Treatment of patients with adult T cell leukemia/lymphoma with cord blood transplantation: a Japanese nationwide retrospective survey. Biol Blood Marrow Transplant. 2014;20:1968–74.

    Article  PubMed  Google Scholar 

  11. Nakamura T, Oku E, Nomura K, Morishige S, Takata Y, Seki R, et al. Unrelated cord blood transplantation for patients with adult T-cell leukemia/lymphoma: experience at a single institute. Int J Hematol. 2012;96:657–63.

    Article  PubMed  Google Scholar 

  12. Fukushima T, Itonaga H, Moriuchi Y, Yoshida S, Taguchi J, Imaizumi Y, et al. Feasibility of cord blood transplantation in chemosensitive adult T-cell leukemia/lymphoma: a retrospective analysis of the Nagasaki Transplantation Network. Int J Hematol. 2013;97:485–90.

    Article  PubMed  Google Scholar 

  13. Horwitz ME, Morris A, Gasparetto C, Sullivan K, Long G, Chute J, et al. Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. Biol Blood Marrow Transplant. 2008;14:591–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yamamoto H, Uchida N, Yuasa M, Kageyama K, Ota H, Kajiet D, et al. A novel reduced-toxicity myeloablative conditioning regimen using full-dose busulfan, fludarabine, and melphalan for single cord blood transplantation provides durable engraftment and remission in nonremission myeloid malignancies. Biol Blood Marrow Transplant. 2016;22:1844–50.

    Article  CAS  PubMed  Google Scholar 

  15. Shimoni A, Hardan I, Shem-Tov N, Rand A, Herscovici C, Yerushalmi R, et al. Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia. 2007;21(10):2109–16.

    Article  CAS  PubMed  Google Scholar 

  16. Baron F, Labopin M, Peniket A, Jindra P, Afanasyev B, Sanz MA, et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015;121(7):1048–55.

    Article  CAS  PubMed  Google Scholar 

  17. Damlaj M, Alkhateeb HB, Hefazi M, Partain DK, Hashmi S, Gastineau DA, et al. Fludarabine-busulfan reduced-intensity conditioning in comparison with fludarabine-melphalan is associated with increased relapse risk in spite of pharmacokinetic dosing. Biol Blood Marrow Transplant. 2016;22(8):1431–9.

    Article  CAS  PubMed  Google Scholar 

  18. Eapen M, Brazauskas R, Hemmer M, Perez WS, Steinert P, Horowitz MM, et al. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018;2(16):2095–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  20. Horwitz S, O’Connor OA, Pro B, Illidge T, Fanale M, Advani R, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;19(393):229–40.

    Article  Google Scholar 

  21. Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016;34:3426–33.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all patients struggling with this difficult disease, as well as all nurses and other healthcare providers at our institution. This work was supported in part by the practical research programs of the Japan Agency for Medical Research and Development (AMED) under Grant number 20ck0106616h0001 and 20ck0106482h0002.

Funding

The authors have nothing to disclose.

Author information

Authors and Affiliations

  1. Department of Hematology, Imamura General Hospital, 11-23 Kamoikeshinmachi, Kagoshima, 890-0064, Japan

    Nobuaki Nakano, Yoshifusa Takatsuka, Ayumu Kubota, Masahito Tokunaga, Takayoshi Miyazono, Tomohisa Tabuchi, Jun Odawara, Mayumi Tokunaga, Torahiko Makino, Shogo Takeuchi, Yoshikiyo Ito & Atae Utsunomiya

Authors
  1. Nobuaki Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshifusa Takatsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayumu Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masahito Tokunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takayoshi Miyazono
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomohisa Tabuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Odawara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mayumi Tokunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Torahiko Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shogo Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshikiyo Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Atae Utsunomiya
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NN, YT, and AU designed the research and wrote the manuscript. NN performed statistical analysis. NN, YT, AK, Masahito T, Takayoshi M, TT, JO, ST, and YI performed CBT and treated the patients. NN, YT, AK, Masahito T, Takayoshi M, TT, JO, Mayumi T, Torahiko M, ST, YI, and AU wrote the draft of the manuscript. All the authors contributed to the final version.

Corresponding author

Correspondence to Nobuaki Nakano.

Ethics declarations

Conflict of interests

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 165 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakano, N., Takatsuka, Y., Kubota, A. et al. Cord blood transplantation with a reduced-intensity conditioning regimen using fludarabine and melphalan for adult T-cell leukemia/lymphoma. Int J Hematol 113, 861–871 (2021). https://doi.org/10.1007/s12185-021-03102-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-021-03102-0

Keywords

Search

Navigation