Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

HLA-mismatched microtransplantation for relapsed or refractory acute myeloid leukemia as a bridge to allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 1684–1686 (2020)Cite this article

Subjects

Patients with relapsed or refractory acute myeloid leukemia (AML) have a poor prognosis and are generally ineligible for allogeneic blood or marrow transplantation (alloBMT) [1]. A novel cell therapy of leukemia comprises the administration of nonablative chemotherapy followed by infusion of leukapheresed peripheral blood cells (PBCs) from a healthy, HLA-mismatched related donor. This therapy, called “microtransplantation”, has been used to treat patients at initial diagnosis [2] or as consolidation of remission [3] but has rarely been used to treat relapsed or refractory leukemia [4]. Here, we report on three patients with relapsed or refractory AML treated with microtransplantation as a bridge to alloBMT.

Case 1: A 19-year-old woman with AML failed to achieve remission after induction with idarubicin and cytarabine or after re-induction with daunorubicin and cytarabine. She then received mitoxantrane and cytarabine followed in 72 h by infusion of leukapheresed, filgrastim-mobilized PBCs containing 50 million CD3+ T cells/kg of recipient body weight from a healthy, fully HLA-mismatched unrelated male donor (Table 1). Treatment was complicated by grade II cytokine release syndrome. Bone marrow aspiration on day 30 following cell infusion revealed complete remission and 100% female cells. She declined alloBMT initially and died a year later, after a salvage, HLA-haploidentical BMT for relapsed disease.

Table 1 HLA typing of patient and donors
Full size table

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730–8.

    Article  Google Scholar 

  2. Guo M, Hu KX, Yu CL, Sun QY, Qiao JH, Wang DH, et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood. 2011;117:936–41.

    Article  CAS  Google Scholar 

  3. Guo M, Hu KX, Liu GX, Yu CL, Qiao JH, Sun QY, et al. HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leukemia: long-term follow-up. J Clin Oncol. 2012;30:4084–90.

    Article  Google Scholar 

  4. Punwani N, Merin N, Mohrbacher A, Yaghmour G, Sano A, Ramezani L, et al. Unrelated HLA mismatched microtransplantation in a patient with refractory secondary acute myeloid leukemia. Leuk Res Rep. 2018;9:18–20.

    PubMed  PubMed Central  Google Scholar 

  5. Othus M, Appelbaum FR, Petersdorf SH, Kopecky KJ, Slovak M, Nevill T, et al. Fate of patients with newly diagnosed acute myeloid leukemia who fail primary induction therapy. Biol Blood Marrow Transplant. 2015;21:559–64.

    Article  Google Scholar 

  6. Rubio MT, Saito TI, Kattleman K, Zhao G, Buchli J, Sykes M. Mechanisms of the antitumor responses and host-versus-graft reactions induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: a critical role for recipient CD4+ T cells and recipient leukocyte infusion-derived IFN-{gamma}-producing CD8+ T cells. J Immunol. 2005;175:665–76.

    Article  CAS  Google Scholar 

  7. Symons HJ, Levy MY, Wang J, Zhou X, Zhou G, Cohen SE, et al. The allogeneic effect revisited: exogenous help for endogenous, tumor-specific T cells. Biol Blood Marrow Transplant. 2008;14:499–509.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge Drs Vikram Mathews and Shivali Ahlawat for their help.

Author information

Author notes

  1. These authors contributed equally: Neeraj Sidharthan, Ephraim Fuchs

Authors and Affiliations

  1. Department of Hematology, Blood and Marrow Transplantation, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India

    Neeraj Sidharthan, Manoj Unni, Pavankumar Boyella, Raghuveer Prabhu & Rema Ganapathy

  2. Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    Ephraim Fuchs

  3. Amirta Centre for Nanosciences and Molecular medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India

    Ullas Mony

  4. Department of Transfusion Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India

    Veena Shenoy

  5. Division of Hematopathology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India

    Geeta Vidyadharan

Authors
  1. Neeraj Sidharthan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ephraim Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manoj Unni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ullas Mony
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pavankumar Boyella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Raghuveer Prabhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rema Ganapathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Veena Shenoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Geeta Vidyadharan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neeraj Sidharthan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all subjects.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sidharthan, N., Fuchs, E., Unni, M. et al. HLA-mismatched microtransplantation for relapsed or refractory acute myeloid leukemia as a bridge to allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 1684–1686 (2020). https://doi.org/10.1038/s41409-019-0761-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0761-4

Search

Advanced search

Quick links