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Prior history of HLA-mismatched stem cell transplantation is a risk factor for graft failure in HLA-haploidentical transplantation

Bone Marrow Transplantation volume 52, pages 323–325 (2017)Cite this article

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Graft failure is one of the major life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-SCT). HLA-mismatched SCT is associated with high incidence of GVHD and graft failure.1, 2 Recently, HLA-haploidentical SCT (haploSCT) using post-transplant cyclophosphamide (PTCy-haploSCT) has been increasingly performed.3, 4 It has been suggested that hematopoietic progenitors are resistant to cyclophosphamide due to high expression of aldehyde dehydrogenase, which convert cyclophosphamide to the inactive metabolites,5 and the rate of graft failure is acceptable with around 5% after PTCy-haploSCT.6, 7, 8, 9, 10 PTCy-haploSCT could be readily performed as the second or salvage SCT in relapsed or rejected patients after allo-SCT who lack an HLA-compatible related or unrelated donors.10, 11 However, risks of graft failure after repetitive allo-SCT are not well documented and it remains to be investigated weather a history of prior allo-SCT could be a risk factor for graft rejection. We conducted a prospective multicenter phase II study (JSCT-Haplo13: UMIN-CTR UMIN000010316) of post-transplant cyclophosphamide-based HLA-haploidentical PBSC transplantation (PBSCT).10 Written informed consents were obtained from patients in accordance with the Declaration of Helsinki. In this report, we discuss risks of graft failure in patients with a history of prior allo-SCT.

JSCT-Haplo13 study included 31 patients with hematologic malignancies. Details of patients characteristics and transplant procedures were reported previously.10 There were no patients with aplastic anemia. Positivity for donor-specific antibodies (DSA) was one of the exclusion criteria of JSCT-Haplo13 study. DSA were checked before PTCy-haploSCT once, and all the patients were negative for DSA in this study. Graft failure was defined as alive on day 28 with absolute neutrophil count<0.5 × 109/L and 1 patient who died by day 28 after SCT were excluded in the current analysis.

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References

  1. Beatty PG. Role of Histocompatibility Antigens in the Development of Graft-Versus Host Disease In: Ferrara JLM, Deeg HJ, Burakoff SJ (eds). Graft-vs-Host Disease 2nd edn. Marcel Dekker, Inc.: New York, NY, USA, 1997, pp 607–614.

    Google Scholar 

  2. Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med 1989; 320: 197–204.

    Article  CAS  Google Scholar 

  3. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    Article  CAS  Google Scholar 

  4. Al-Homsi AS, Roy TS, Cole K, Feng Y, Duffner U . Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. Biol Blood Marrow Transplant 2015; 21: 604–611.

    Article  CAS  Google Scholar 

  5. Emadi A, Jones RJ, Brodsky RA . Cyclophosphamide and cancer: golden anniversary. Nat Rev. Clin Oncol 2009; 6: 638–647.

    Article  CAS  Google Scholar 

  6. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant 2013; 19: 117–122.

    Article  CAS  Google Scholar 

  7. Raj K, Pagliuca A, Bradstock K, Noriega V, Potter V, Streetly M et al. Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant 2014; 20: 890–895.

    Article  Google Scholar 

  8. Castagna L, Bramanti S, Furst S, Giordano L, Crocchiolo R, Sarina B et al. Nonmyeloablative conditioning, unmanipulated haploidentical SCT and post-infusion CY for advanced lymphomas. Bone Marrow Transplant 2014; 49: 1475–1480.

    Article  CAS  Google Scholar 

  9. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK et al. Total body irradiation-based myeloablative haploidentical stem cell transplantation is a safe and effective alternative to unrelated donor transplantation in patients without matched sibling donors. Biol Blood Marrow Transplant 2015; 21: 1299–1307.

    Article  Google Scholar 

  10. Sugita J, Kawashima N, Fujisaki T, Kakihana K, Ota S, Matsuo K et al. HLA-haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide after busulfan-containing reduced-intensity conditioning. Biol Blood Marrow Transplant 2015; 21: 1646–1652.

    Article  Google Scholar 

  11. Tischer J, Engel N, Fritsch S, Prevalsek D, Hubmann M, Schulz C et al. Second haematopoietic SCT using HLA-haploidentical donors in patients with relapse of acute leukaemia after a first allogeneic transplantation. Bone Marrow Transplant 2014; 49: 895–901.

    Article  CAS  Google Scholar 

  12. Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE et al. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 2015; 125: 2855–2864.

    Article  CAS  Google Scholar 

  13. Atsuta Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, Kai S et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood 2009; 113: 1631–1638.

    Article  Google Scholar 

  14. Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J et al. Comparison of outcomes of 8/8 and 7/8 allele-matched unrelated bone marrow transplantation and single-unit cord blood transplantation in adults with acute leukemia. Biol Blood Marrow Transplant 2016; 22: 330–338.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the grant from Regional Medicine Research Foundation (Tochigi, Japan), North Japan Hematology Study Group (NJHSG) and Japan Agency for Medical Research and Development (AMED, 16ek0510012h0002).

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Authors and Affiliations

  1. Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    J Sugita & T Teshima

  2. Department of Hematology/Onclogy, Kyushu University Hospital, Fukuoka, Japan

    T Miyamoto

  3. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    N Kawashima

  4. Department of Hematology, Saiseikai Maebashi Hospital, Maebashi, Japan

    N Hatsumi

  5. Department of Hematology, Takatsuki Red Cross Hospital, Takatsuki, Japan

    N Anzai

  6. Department of Hematology, Osaka Red Cross Hospital, Osaka, Japan

    H Kaneko

  7. Department of Hematology/Nephrology / Rheumatology, Akita University Hospital, Akita, Japan

    M Nara

  8. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    K Minauchi

  9. Department of Medicine, Karatsu Higashimatsuura Medical Center, Karatsu, Japan

    M Harada

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  1. J Sugita
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on behalf of the Japan Study Group for Cell Therapy and Transplantation (JSCT)

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Correspondence to T Teshima.

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Sugita, J., Miyamoto, T., Kawashima, N. et al. Prior history of HLA-mismatched stem cell transplantation is a risk factor for graft failure in HLA-haploidentical transplantation. Bone Marrow Transplant 52, 323–325 (2017). https://doi.org/10.1038/bmt.2016.278

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